View
222
Download
3
Category
Preview:
Citation preview
Farmakoterapi Obat sistem hepato-bilier
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVERLiver blood flow a portal vein (80) nutrients amp xenobiotics from GIT
b hepatic artery (20) oxygen metabolite amp circulating xenobiotics
potentially suffer from intoxication
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
Physiological role
Nutrients metabolism carbohydrates lipids and proteins
Synthesis and secretes bilewater ions lipids (bile salts) and bile pigments
(bilirubin)
Synthesis protein enzymesalbumin cytochrome P450s transaminase
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVER
Nutrient metabolism
a Carbohydrate metabolism synthesis glycogen from glucose and reverse
b Lipid metabolismtriglyceride FFA HDL LDL VLDL
c Protein metabolismenzymes albumin amino acid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
xenobiotic metabolism
a enhance excretionby change any substance become polar hydrophilic
b inactivate detoxicationit is often (but not always) achieved sometime activation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVERLiver blood flow a portal vein (80) nutrients amp xenobiotics from GIT
b hepatic artery (20) oxygen metabolite amp circulating xenobiotics
potentially suffer from intoxication
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
Physiological role
Nutrients metabolism carbohydrates lipids and proteins
Synthesis and secretes bilewater ions lipids (bile salts) and bile pigments
(bilirubin)
Synthesis protein enzymesalbumin cytochrome P450s transaminase
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVER
Nutrient metabolism
a Carbohydrate metabolism synthesis glycogen from glucose and reverse
b Lipid metabolismtriglyceride FFA HDL LDL VLDL
c Protein metabolismenzymes albumin amino acid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
xenobiotic metabolism
a enhance excretionby change any substance become polar hydrophilic
b inactivate detoxicationit is often (but not always) achieved sometime activation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
Physiological role
Nutrients metabolism carbohydrates lipids and proteins
Synthesis and secretes bilewater ions lipids (bile salts) and bile pigments
(bilirubin)
Synthesis protein enzymesalbumin cytochrome P450s transaminase
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVER
Nutrient metabolism
a Carbohydrate metabolism synthesis glycogen from glucose and reverse
b Lipid metabolismtriglyceride FFA HDL LDL VLDL
c Protein metabolismenzymes albumin amino acid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
xenobiotic metabolism
a enhance excretionby change any substance become polar hydrophilic
b inactivate detoxicationit is often (but not always) achieved sometime activation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVERLIVER
Nutrient metabolism
a Carbohydrate metabolism synthesis glycogen from glucose and reverse
b Lipid metabolismtriglyceride FFA HDL LDL VLDL
c Protein metabolismenzymes albumin amino acid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
xenobiotic metabolism
a enhance excretionby change any substance become polar hydrophilic
b inactivate detoxicationit is often (but not always) achieved sometime activation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER
xenobiotic metabolism
a enhance excretionby change any substance become polar hydrophilic
b inactivate detoxicationit is often (but not always) achieved sometime activation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Parasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation
(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
NABQI hepatotoxic
glutathione
oxidation
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
1 Acute hepatitis (acute viral hepatitis alcoholic
hepatitis)
2 Chronic hepatitis (chronic persistent hepatitis
chronic active hepatitis autoimmune type)
3 Liver cirrhosis (compensated and non-
compensated cirrhosis liver cirrhosis
encephalopathy cirrhosis edema and ascites
bleeding from esophageal varices and cirrhosis
renal failure)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver Diseases - Disorders
4 Special liver cirrhosis
(hemochromatosis Wilson disease
primary biliary cirrhosis)
5 Gallstones
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drugs in Hepatitis1 Acute hepatitis Symptomatic teraphy
cholestyramine reduce pruritus but may cause
hepatotoxicity use this drug as it really needed
corticosteroids no benefit
active immunization hepatitis-B vaccine
passive immunization immune serum globulin
(HBIG) effective side effects
2 Chronic hepatitis corticosteroids or other immunosuppressant avoid
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Cholestyramine
bull Acid bile chelator bull Bind to acid bile in the intestine lumen block acid bile reabsorption
serum bilirubin pruritusbull Unpleasant tastebull May causes diarrhea and abdominal
discomfortbull If pruritus is not controlled by
cholestyramine antihistamine is recommended
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Corticosteroids
bull May have a benefit in cholestasis secondary to hepatitis-A viral infection(not for other type of viral hepatitis)
bull May suppress RES decrease self protection toward infection
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Chronic active hepatitis
bull Autoimmune hepatitis characterized by histopathological feature chronic hepatitis presence of autoantibody
bull Interferon-a inhibit viral replication (+ 40 of chronic hepatitis-B) may cause influenza like symptom bone marrow suppression depression irritable
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
LIVER CIRRHOSIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull A pathological features caused by irreversible chronic injury of the hepatic parenchyma
bull Extensive fibrosisin association with regenerative nodules
bull As a final common pathwayof many types of chronic liver injury
bull Clinical featuresreflect the severity of hepatic damage rather than the etiology of underlying liver diseases
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Clinical features of Clinical features of
Liver cirrhosisbull Loss of functioning hepatocellular mass
jaundice edema coagulopathy metabolic abnormalities
bull Fibrosis and distorted vasculature portal hypertension and its sequelae(gastroesophagel varices and splenomegaly)
bull Ascites and hepatic encephalopathy resulted from both hepatocellularinsufficiency and portal hypertension
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Alcohol induced hepatic lesion
1 Alcoholic fatty liver accumulation of fat in the liver result from an impairment of fatty acid oxidation
increase uptake and esterification to form triglyceride and diminished lipoprotein biosynthesis
2 Alcoholic hepatitishepatocyte degeneration and necrosis ballooned cells infiltrate alcoholic hyaline
3 Alcoholic cirrhosisdestruction of hepatocytes and fibroblast collagenization
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull compensated cirrhosis
- regularly reviewed for sign of hepatocellular
failure serum analysis for LFT
- long term care includes control of ascites
- avoid drugs that induce coma
do not give unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosisbull decompensated cirrhosis
- diet should be as nutritious as possible high protein diet
(provided that there is no evidence of precoma or coma)
- oral vitamin K if there is high prothrombin time
avoid unnecessarily drugs
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver cirrhosis
bull Edema and ascites- mobilise intraperitoneal fluid decrease Na+ dietary intake
(1 ndash 15 gday 40 ndash 60 mmolday)
- diuretics (furosemide or spironolacton if needed)
avoid dehydration if diuretic is used
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Hepatic encephalopathy
- oral lactulose acidifying the colonic contents
(reducing absorption of ammonia and possible toxins)the dose is increased until desired effect is obtained
- neomycin (reduce urease producing intestinal
bacteria)
avoid unnecessarily drugs
Liver cirrhosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
HEPATOTOXICITY
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Manifestation of HEPATOTOXICITY
Fatty liver2 Hepatitic reactions 3 Obstructive jaundice cholestatic jaundice
4 Liver necrosis5 Liver cirrhosis6 Liver cancer
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Fatty Liver1 Fatty Liveruptake FFA + glycerol triglyceride +
phospholipidscholesterolprotein
VLDL- triglyceride- chlolesterol- phospholipid- protein
Increase in- FA synthesis- triglyceride synthesis
Defect of - lipid metebolism- protein synthesis
Fatty liver
ethionine CCl4
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Drug induced Fatty LiverDrug induced Fatty Liver
1 Carbontetrachloride (CCl4)2 Tetracycline3 Ethionine 4 Ethanol chronic5 Phalotidine alkaloids
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
2 Hepatitic Reactionxenobiotics
haptens
hepatocytes hypersensitive reactions
hepatitic reaction
symptoms
reactive metabolite
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(non dose dependent)
1 Carbimazole methylthiouracil (antithyroiddrugs)
2 Benzodiazepines (anxiolytics anticonvulsant)
3 Clavulanic acid (b-lactamase inhibitor)
4 Imidazole (ie ketokonazole antimycotics)
5 Sulphonylurea (oarl antidiabetics tolbutamideglibenclamide chlopropamide)
6 Tricyclic antidepressants (imipramine amitryptiline desipramine iprindole)
7 Phenothiazines (ie chlorpromazine antipsychotics)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
3 Intrahepatic cholestasis(dose dependent)
1 Anabolic steroids (methyltestosterone norethindrolone)
2 Azatrioprine (antiviral)3 Mercaptopurine (antimetabolite for acute leukemia)
4 Oestrogen (contraceptive agents)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
4 4 Drug Drug toxin inducedtoxin inducedLIVER NECROSIS
1 Aflatoxin2 INH3 Carbontetrachloride4 Paracetamol5 Chloroform 6 Tetracycline7 Dinitrophenol8 Ethionine9 Halothane10 Ibuprofen11 Indomethacin12 Amanita phaloides
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Liver NecrosisLiver NecrosisParasetamol
NABQI conjugation(N-cetylbenzoquinoneimine) (sulphate or glucuronate)
conjugation(sulphate or glucuronate)
renal excretion renal excretion
7 ndash 10 90 ndash 93
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
NABQI (n(n--acetylbenzoquinoneimineacetylbenzoquinoneimine))
NABQI
binding (covalent) to celluler hepatic proteins
damage endoplasmic reticulumswelling mitochondriadestruction of nucleus
mesruption of plasma membrane
cell necrosis
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Acute hepatocellular damage (non dose dependent)(non dose dependent)1 INH pyrazinamide rifampicin
(antituberculosis)2 Carbamazepine (muscle realxant
anticonvulsant)3 Halothane (inhalant general anesthetics)4 Imidazole (ie ketokonazole antimycotics)5 Ibuprofen indomethacin (NSAIDs)6 Methyldopa (antihypertensive)7 MAO inhibitor (ie desipramine
antidepresant)8 Barbiturate (hypnotics anticonvulsant)7 Sulfonamide (sulfamethoxazol
chemotherapeutics)Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
1 Alcohol (beverage)2 Amiodarone (cardiac stimulant)3 Azatrioprine (antiviral)4 Chlorambucil (alkylating agent ndash for CLL)5 Hydrocarbons (glue glue sniffing)6 Overdose iron salt (antianemics)a7 Methotrexate (antimetabolite antifolic acid ndash for cancer)8 Acetaminophen (analgesics ndash antipyretics)7 Tetracycline (intravenous large dose)
Acute hepatocellular damage ( dose dependent)( dose dependent)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
CHOLELITHIASIS(Gallbladder stone)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
bull Previous cholecystitis bull Rapid weight loss during treatment of overweight morbid-obesity cholesterol is the main substance forms the stone
bull Ursodiol decrease cholesterol secretion into the bile decrease intestine cholesterol absorption increase bile flow cholesterol stone disolve
bull Opioid analgesics analgesia increase duct smooth muscle tonemasking effect stone captures duct rupture spasmolytics (hyoscin papaverin)
bull Antibiotics antiinflammatory drugs
CHOLELITHIASIS
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Drug Induced Liver Injury andIts Patterns
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Navarro V J et al N Engl J Med 2006354731-739
Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
TerimaTerima kasihkasihhelliphelliphelliphellip
Create PDF files without this message by purchasing novaPDF printer (httpwwwnovapdfcom)
Recommended