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7/30/2019 Gastroesophagial Reflux Disease Seminar
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Introduction Gastrointestinal tract and wall
Clinical relevance
Gastric motility and Gastric glands Gastroesophageal reflux disease (GERD)
Acid secretion and regulation
Pharmacological targets for (GERD)
Recent drugs
Conclusion
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NEURONAL PLEXUSESdiabetes mellitus
connective tissue disorders
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ALTERED PERISTALSISPregnancy
Obstruction
IMPROPER MIXING OFFOOD
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JUICES VOLUME PH
SALIVA 1000ml 6-7
GASTRIC 1500ml 1-3.5
PANCREATIC 1000ml 8-8.3
BILE,BRUNNERS 1200ml 7-8
INTESTINES 2000ml 7.5-8
TOTAL 6700ml
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QUANTITY OF SECRETION
PHASES OF SECRETION
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MUCOUS NECK CELLS
PARIETAL CELL
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Chronic relapsing condition
Significant morbidity
Estimated lifetime prevalence of 25-35 %
44% have heartburn once a month
14% have weekly symptoms
7 % have daily symptoms
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Caffeine
Peppermint
Fatty foods
Chocolate
Spicy foods
Citrus fruits
Tomato
Alcohol
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History
Response to a PPI
Radiologic findings Endoscopy
Ambulatory pH monitoring
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Pyrosis (Heartburn) regurgitation
or both.
High specificity, low sensitivity
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Atypical chestpain
Hoarseness
Nausea
Cough
Odynophagia
Globus sensation
Onset after age 45
Recurrent
laryngitis Subglottic stenosis
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Omeprazole 40 mg BID X 14 days as
specific and sensitive for diagnosis as
24 hour ph monitoring
Failure to respond warrants further
investigation of patients symptoms
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Diagnostic gold standard
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Esophagitis Strictures
Ulcerations
Barretts esophagus
Adenocarcinoma
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Dysphagia Odynophagia
Early satiety
GI bleeding
Iron deficiency anemia
Vomiting
Weight loss
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Head of bed elevated by six inches
Decreased fat intake Smoking cessation
Weight loss
Avoidance of recumbency for 3 hourspost-prandially
Avoidance of large meals
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OMEPRAZOLE RABEPRAZOLE
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OMEPRAZOLE
ESOMEPRAZOLE
LANSOPRAZOLE
RABEPRAZOLE
PANTOPRAZOLE
TENATOPRAZOLE
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PRODRUG
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ABSORBED INTO SYSTEMIC CIRCULATION
DIFFUSES INTO PARIETAL CELLS
ACCUMULATES IN SECRETORY CANALICULI
ACTIVATED TO TETRACYCLIC SULFENAMIDE
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BINDS COVALENTLY TO ACID - PUMP
IRREVERSIBLY INHIBITS THE PUMP
ACID SECRETION IS SUPPRESSED
BOTH BASAL AND STIMULATED
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Provides acid suppression for 24-48 hours Acid secretion resumes after new enzyme
synthesis
Block final step in acid secretion Metabolized by CYP2C19, CYP3A4
Dose reduction is recommended for
esomeprazole and lansoprazole in hepaticdisease
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PHARMACOKINETICS
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Prodrugs
Administered 30 minutes before food
Are highly plasma bound
Maximal acid secretion suppressionrequires several doses
Single daily dosing may need 2-5 days
Lansoprazole is preferred in pregnancy
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Nausea
Abdominal pain
Constipation Flatulence
Diarrhea
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Hypergastrinemias
Gastrointestinal tumors
Carcinoid tumors Vitamin B12 malabsorption
Campylobacter infection
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Decrease clearance of
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Disulfiram
Phenytoin
Imipramine
Tacrine
Theophylline
Ketoconazole
Ampicillin Esters
Iron salts
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CIMETIDINE FAMOTIDINE
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CIMETIDINE
RANITIDINE
FAMOTIDINE
NIZATIDINE
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PHARMACOKINETICS
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Rapid oral absorption
Peak concentration achieved in 1-3 hours
Absorption enhanced by food
Small % are protein bound Major site for excretion is kidney
Hemodialysis nor peritoneal dialysis clears
significant amount of drug
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Head ache
Diarrhea
Drowsiness
Fatigue
Muscular pain
Constipation
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Galactorrhea
Gynacomastia
Impotence Reduced sperm
count
Thrombocytopenia
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Cimetidine inhibits CYP1A2,P2C9,P2D6
Ranitidine inhibits CYP hepatic
Famotidine and Nizatidine have no significant
drug intractions
Slight increase in blood alcohol
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Decreased therapeutic effect
Tolerance can develop within 3 days
Resistant to increased doses ofmedication
May be due to secondary
hypergastrenemia
PPI H2RA
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-MORE POTENT
-IRREVERSIBLE
INHIBITOR
-GIVEN BEFORE FOOD
-METABOLISED IN LIVER
-REDUCES BOTH
SECRETION
-LESS POTENT
-REVERSIBLE
INHIBITORS
-GIVEN WITH FOOD
-HEPATIC 10% -35%
-REDUCES BASAL
SECRETION
PPI H2RA
A
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-EXTENSIVELY PROTEIN
BOUND
-TOLERANCE NOT SEEN
-HEALING RATES AT
4 WEEKS IS 80%
-STRICTURES RESPOND
BETTER
-SMALL % PROTEIN BOUND
-TOLERANCE SEEN
-HEALING RATES AT
4 WEEKS IS 50%
-STRICTURES RESPOND
POORLY
A
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Metoclopramide
Domperidone
Cisapride
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Increases gastric motility
Action is independent of vagal
innervations
LES tone is increased
No effect on gastric secretion
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D2 selective antagonist
5HT4 receptor agonist
5HT3 antagonist Sensitization of muscarinic
receptors on smooth muscle
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PHARMACOKINETICS
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Rapidly absorbed orally
Crosses blood brain barrier
Half life is 4-6 hours
Secreted in milk
Partly conjugated in liver
Excreted in urine
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Sedation Dizziness
Diarrhea
Muscle dystonias Galactorrhoea
Gynacomastia
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Hastens absorption of Aspirin
Hastens absorption of Diazepam
Decreases absorption of Digoxin
Bioavailability of Cimetidine is reduced
Abolishes the therapeutic effect ofLevodopa
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Chemically related to haloperidol
Pharmacologically related to
Metaclopramide
Crosses BBB poorly
EPS are rare
Oral bioavailability is 15%
Plasma t is 7.5 hours
Cardiac arrhythmias can develop onrapid iv injection
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SODIUM BICARBONATE SODIUM CITRATE
MAGNESIUM SALTS
ALUMINIUM HYDROXIDE GEL MEGALDRATE
CALCIUM CARBONATE
SIMETHICONE
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Water soluble Acts instantaneously
Short duration
Absorbed systemically May produce alkalosis
Produce CO2 in stomach
Rebound acid production can occur
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Very potent Rapidly acting
Releases CO2 and causes discomfort
Can cause hypercalcaemia,calciumstones,calciuria,alkalosis
Can cause milk alkali syndrome with
milk
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Fast (mag salts) slow (alum salts) Laxative (mag salts) constipation
(alum salts)
Gastric emptying is hastened (magsalts) delayed (alum salts)
Toxicity is counteracted
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Is a surfactant
Decreases foaming
Is indicated in many antacid preparations
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Cholecystokinin A receptor antagonist
Improves gastric emptying
Suppresses transient relaxation of LES Investigations in Europe are suggestive
of its use in GERD
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Amino guanidine indole
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Partial 5-HT4 agonist
Negligible affinity for receptor subtypes Stimulates motility in GI tract
Should be taken on empty stomach
98% plasma bound t is 11hours
Diarrhea and headache are side effects
No significant cardio-toxicity reported
No clinically relevant drug interactions
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1)THE PHARMACOLOGICAL BASIS OF
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THERAPEUTICS
2)CLINICAL PHARMACOLOGYBENNETTAND BROWN
3)MATINDALE 33rd EDITION
4)LIPPINCOTS ILLUSTRATEDPHARMACOLOGY
5)BERTRAM KATZUNG 10 EDITION
6)GENERAL PHARMACOLOGICAL PRINCIPALSKD TRIPATHI
7) HARRISONS TEXT BOOK OF INTERNALMEDICINE
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8) DAVIDSONS PRINCIPLES AND PRACTICE
OF MEDICINE9) API TEXT BOOK OF INTERNAL MEDICINE
10)TEXT BOOK OF PREVENTIVE MEDICINE
PARK
11)CURRENT MEDICAL DIGNOSIS AND
TREATMENT
12)BASICS OF PHYSIOLOGYGYTON
13)TEXT BOOK OF PHYSIOLOGY-GANONG
14)GASTROENTROLOGY AND HEPATICDISEASES VOLUME 1-NORMAN DAVID
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15)GRAYS ANATOMY
16)BIOLOGICAL HEALTH DEPARTMENTCALIFORNIA STATE UNIVERSITY
17)CASE STUDIESAIIMS NEW DELHI
18)DEPARTMENT OF GASTROENTROLOGYUMC MANGALORE