Antiulcer Drugs

ANTI ULCER ANTI ULCER DRUGSDRUGS

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INTRODUCTIONINTRODUCTION

► Ulcers are sores or open wounds that occur Ulcers are sores or open wounds that occur on the skin or along the lining of the on the skin or along the lining of the digestive tract due to loss of tissue. digestive tract due to loss of tissue.

► Peptic ulcers are the most common types of Peptic ulcers are the most common types of ulcers .ulcers .

► The lifetime risk for developing a peptic The lifetime risk for developing a peptic ulcer is approximately 10%.ulcer is approximately 10%.

► In the In the United States about 4 million people about 4 million people have active peptic ulcers and about 350,000 have active peptic ulcers and about 350,000 new cases are diagnosed each year. new cases are diagnosed each year.

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TYPES OF ULCERSTYPES OF ULCERS

► Peptic Ulcers:: Peptic ulcers is a Peptic ulcers is a broad term which includes broad term which includes ulcers of digestive tract in the ulcers of digestive tract in the stomach or the duodenum.stomach or the duodenum.

► The causative agent is The causative agent is infection caused by the infection caused by the bacteria H. pylori or reaction to bacteria H. pylori or reaction to certain medicines like non-certain medicines like non-steroidal anti-inflammatory steroidal anti-inflammatory drugs (NSAIDs)drugs (NSAIDs)

► Ulcers of the duodenum are Ulcers of the duodenum are called called duodenal ulcers, , whereas those in the stomach whereas those in the stomach are called stomach ulcers or are called stomach ulcers or gastric ulcers Visit :www.bpharmstuf.com

MOUTH ULCERSMOUTH ULCERS Sores that develop in the inner lining of Sores that develop in the inner lining of

the mouth are referred to as mouth the mouth are referred to as mouth ulcers.ulcers.

Anemia, measles, viral infection, oral Anemia, measles, viral infection, oral candidiasis, chronic infections, throat candidiasis, chronic infections, throat cancer, mouth cancer and vitamin B cancer, mouth cancer and vitamin B deficiency are some of the common deficiency are some of the common causes of ulcers or sores in the mouth.causes of ulcers or sores in the mouth.

These These mouth sores are round or oval in are round or oval in shape and white, yellow or gray in shape and white, yellow or gray in colour.colour.

These are usually cured within 10-14 These are usually cured within 10-14 days. However, in severe cases it may days. However, in severe cases it may take several weeks for these to heal take several weeks for these to heal completely.completely.


ESOPHAGEAL ULCERSESOPHAGEAL ULCERS► Esophageal ulcers are lesions that Esophageal ulcers are lesions that

occur in the esophagus (the food occur in the esophagus (the food pipe).pipe).

► These most commonly form in the These most commonly form in the end of the food pipe and can be end of the food pipe and can be felt as a pain right below the felt as a pain right below the breastbone in the same area breastbone in the same area where symptoms of heartburn are where symptoms of heartburn are felt.felt.

► Esophageal ulcers are associated Esophageal ulcers are associated with with acid reflux or GERD, or GERD, prolonged use of drugs like prolonged use of drugs like NSAIDs, and smoking.NSAIDs, and smoking.


GENITAL ULCERSGENITAL ULCERS

► Genital ulcers are caused due to Genital ulcers are caused due to sexually transmitted diseases like sexually transmitted diseases like syphilis, genital herpes, or thrush. syphilis, genital herpes, or thrush.

► Non-sexual causes of genital Non-sexual causes of genital ulcers are infections caused by ulcers are infections caused by yeast, scabies, pyoderma genital yeast, scabies, pyoderma genital trauma trauma

and Behcet's disease. and Behcet's disease. ► Genital ulcers manifest as single Genital ulcers manifest as single

or multiple ulcers which are or multiple ulcers which are mostly painful.mostly painful.


PRESSURE SORESPRESSURE SORES

► These lesions are caused in These lesions are caused in patients who are confined to bed patients who are confined to bed due to some debilitating illness or due to some debilitating illness or are on their way to recovery in are on their way to recovery in hospital.hospital.

► In the initial stages a bedsore In the initial stages a bedsore manifests itself as a persistent manifests itself as a persistent area of red skin that hurts and area of red skin that hurts and feels warmfeels warm

► As the severity increases there is As the severity increases there is loss of the upper layer of skin and loss of the upper layer of skin and subsequent damage to the subsequent damage to the underlying tissue.underlying tissue.


Causes of ulcerCauses of ulcer Peptic ulcer disease was once thought of simply Peptic ulcer disease was once thought of simply

as a problem of too much acid and stress.as a problem of too much acid and stress. It results of an imbalance between digestive It results of an imbalance between digestive

fluids (hydrochloric acid and pepsin) in the fluids (hydrochloric acid and pepsin) in the stomach and duodenum. stomach and duodenum.

Much of that imbalance is clearly related to Much of that imbalance is clearly related to infection with the bacteria infection with the bacteria Helicobacter pyloriHelicobacter pylori ( ( H. pyloriH. pylori ). ).

The other major risk factor for the development The other major risk factor for the development of ulcers is ingestion of nonsteroidal of ulcers is ingestion of nonsteroidal antiinflammatory drugs (NSAIDs) such as antiinflammatory drugs (NSAIDs) such as aspirin.aspirin. Visit :www.bpharmstuf.com

PATHOPHYSIOLOGYPATHOPHYSIOLOGY Peptic ulcer results Peptic ulcer results

probably due to an probably due to an imbalance between imbalance between the aggressive and the aggressive and defensive factors. defensive factors. Increase in acid-pepsin Increase in acid-pepsin secretion and secretion and decrease in mucosal decrease in mucosal resistance appears to resistance appears to be the basic cause for be the basic cause for peptic ulcerationpeptic ulceration

AggressiveAggressive

factorsfactorsDefensiveDefensive

factorsfactors

AcidAcid

PepsinPepsin

HelicobacterHelicobacter

PyloriPylori

NSAIDSNSAIDS

MucousMucous

BicarbonateBicarbonate

ProstaglandinProstaglandinss

Mucous blood Mucous blood flowflow


PATHOPHYSIOLOGYPATHOPHYSIOLOGY


DIAGNOSISDIAGNOSIS► Perform diagnostic tests to see if Perform diagnostic tests to see if

there is an ulcer:there is an ulcer:► ~ Upper endoscopy, which ~ Upper endoscopy, which

involves inserting a small lighted involves inserting a small lighted tube into the stomach to look for tube into the stomach to look for abnormalities. A small sample of abnormalities. A small sample of tissue (biopsy) is removed and tissue (biopsy) is removed and analyzed to confirm diagnosis.analyzed to confirm diagnosis.

► ~ Testing for ~ Testing for H. pyloriH. pylori infection by infection by either a stool sample or by either a stool sample or by obtaining a breath sample. If the obtaining a breath sample. If the test is positive, the patient is test is positive, the patient is treated with antibiotics. If treated with antibiotics. If negative, the focus of the negative, the focus of the evaluation will be on the other evaluation will be on the other causes of peptic ulcer disease, causes of peptic ulcer disease, such as NSAID consumption.such as NSAID consumption.Visit :www.bpharmstuf.com

TREATMENT TREATMENT

Approaches for the treatment of peptic Approaches for the treatment of peptic ulcer areulcer are

Reduction of gastric acid secretionReduction of gastric acid secretion Neutralization of gastric acidNeutralization of gastric acid Ulcer protectivesUlcer protectives Anti-H.pylori drugs Anti-H.pylori drugs


ANTI ULCER DRUGSANTI ULCER DRUGS

REDUCTION OF GASTRIC ACID REDUCTION OF GASTRIC ACID SECRETIONSECRETION

►Histamine antagonist: Cimetidine, Histamine antagonist: Cimetidine, ranitidineranitidine

►Proton pump inhibitors: omeprazole, Proton pump inhibitors: omeprazole, pantaprazolepantaprazole

►Acetyl choline antagonist: pirenzepine, Acetyl choline antagonist: pirenzepine, propanthelinepropantheline

►Prostaglandin analogue: misoprostolProstaglandin analogue: misoprostolVisit :www.bpharmstuf.com

ANTIULCER DRUGSANTIULCER DRUGS

Neutralization of gastric Neutralization of gastric acid(antacids)acid(antacids)

Systemic : Sodium bicarbonate,Sodium citrateSystemic : Sodium bicarbonate,Sodium citrate

Nonsystemic : Magnesium Nonsystemic : Magnesium hydroxide,Aluminium hydroxideshydroxide,Aluminium hydroxides

Ulcer potectivesUlcer potectives : : Sucralfate Sucralfate Anti hlicobacter pylori :Anti hlicobacter pylori :

amoxicillin,clarithromycin,etcamoxicillin,clarithromycin,etcVisit :www.bpharmstuf.com

Histamine antagonistHistamine antagonistCimetidineCimetidine

Cimetidine belongs to a Cimetidine belongs to a class of medications called class of medications called histamine H2-histamine H2-antanists. Histamine is a antanists. Histamine is a

natural chemical that natural chemical that stimulates stomach cells to stimulates stomach cells to produce acid. Histamine produce acid. Histamine H2-antagonists inhibit the H2-antagonists inhibit the action of histamine on the action of histamine on the acid-producing cells of the acid-producing cells of the

stomach and reduce stomach and reduce stomach acid stomach acid

CIMETIDINECIMETIDINE SIDE EFFECTSSIDE EFFECTS; it include ; it include constipation, ,

diarrhea, fatigue, , fatigue, headache, , insomnia, , muscle pain, and vomiting. Major side effects , and vomiting. Major side effects include confusion and hallucinations, include confusion and hallucinations, enlargement of the breasts; impotence.enlargement of the breasts; impotence.

DRUG INTERACTIONS: DRUG INTERACTIONS: Cimetidine may Cimetidine may increase the blood levels of several drugs by increase the blood levels of several drugs by reducing their elimination by the liver. This reducing their elimination by the liver. This interaction may occur between cimetidine and interaction may occur between cimetidine and warfarin (Coumadin), a commonly used blood (Coumadin), a commonly used blood thinning agent thinning agent Visit :www.bpharmstuf.com

CIMETIDINECIMETIDINE

►DOSE: DOSE: 400 mg at bed time400 mg at bed time

►USES: USES: it is used in treatment of duodenal it is used in treatment of duodenal ulcer, ulcer,

Gastric ulcer, stress ulcer, GERD, zollinger Gastric ulcer, stress ulcer, GERD, zollinger ellision ellision

syndromesyndrome


PROTON PUMP INHIBITORSPROTON PUMP INHIBITORSOMEPRAZOLEOMEPRAZOLE► Omeprazole is inactive at neutral pH, but at Omeprazole is inactive at neutral pH, but at

pH<5 rearranges to two charged cationic pH<5 rearranges to two charged cationic forms(a sulphenic acid and a sulphenamide forms(a sulphenic acid and a sulphenamide configurations)that react covalently with SH configurations)that react covalently with SH groups of the H+K+ATPase enzyme and groups of the H+K+ATPase enzyme and inactivate it irreversibly, especially when two inactivate it irreversibly, especially when two molecules of omeprazole react with one molecules of omeprazole react with one molecule of the enzyme. molecule of the enzyme.


OMEPRAZOLEOMEPRAZOLE► SIDE EFFECTS SIDE EFFECTS Stomach Stomach

pain,Diarrhea,Constipation,Dizziness,CoughBpain,Diarrhea,Constipation,Dizziness,CoughBack, Pain,Rash,Hives,Itching,seizuresack, Pain,Rash,Hives,Itching,seizures

► DRUG INTERACTIONDRUG INTERACTION

Omeprazole inhibits oxidation of certain Omeprazole inhibits oxidation of certain drugs: diazepam, phenytion and warfarin drugs: diazepam, phenytion and warfarin levels may be increased. Clarithromycin levels may be increased. Clarithromycin inhibits omeprazole metabolism and inhibits omeprazole metabolism and increases its plasma concentration. It increases its plasma concentration. It reduces bioavailability of ketoconazole reduces bioavailability of ketoconazole


ACETYL CHOLINE ANTAGONISTACETYL CHOLINE ANTAGONIST

Atropinic drugs reduce the volume of Atropinic drugs reduce the volume of gastric juice without raising it’s pH unless there gastric juice without raising it’s pH unless there

is food in stomach to dilute the secreted acid. is food in stomach to dilute the secreted acid. stimulated gastric secretion is less completely stimulated gastric secretion is less completely inhibited. inhibited.

DRUGS:DRUGS: PirenzepinePirenzepine OxyphononiumOxyphononium


ACETYL CHOLINE ACETYL CHOLINE ANTAGONISTANTAGONIST

PIRENZEPINEPIRENZEPINE MECHANISM: MECHANISM: It selectively block M1 muscaranic It selectively block M1 muscaranic

recptors and inhibits gastric secretion. recptors and inhibits gastric secretion. The more likely site of action of The more likely site of action of pirenzepine in stomach intramural pirenzepine in stomach intramural plexuses and ganglionic cells rather plexuses and ganglionic cells rather than the parietal cells themselvesthan the parietal cells themselves

DOSEDOSE Pirenzepine 50mg orally twice or thrice Pirenzepine 50mg orally twice or thrice

daily for 4-6 weeksdaily for 4-6 weeksVisit :www.bpharmstuf.com

PirenzepinePirenzepine► SIDE EFFECTS:SIDE EFFECTS:

Dry mouth, blurred vision, , blurred vision, drowsiness, dizziness, nausea or loss of drowsiness, dizziness, nausea or loss of appetite may occurappetite may occur

the first few days as your body adjusts to the first few days as your body adjusts to the medication. the medication.

► USESUSES

The medication is used in the treatment of The medication is used in the treatment of ulcersulcers


PROSTAGLANDIN ANALOGUEPROSTAGLANDIN ANALOGUE

prostaglandins are produced in the gastric prostaglandins are produced in the gastric

mucosa and appear to serve a protective role by mucosa and appear to serve a protective role by inhibiting acid secretion and promoting mucus inhibiting acid secretion and promoting mucus

and bicarbonate secretion. In addition, PGs inhibitsand bicarbonate secretion. In addition, PGs inhibits

gastrin production, increase mucosal blood flow gastrin production, increase mucosal blood flow

and probably have an ill defined cytoprotective and probably have an ill defined cytoprotective

action. action.

DRUGS:DRUGS: MisoprostolMisoprostol

Colloidal bismuth subcitrate Colloidal bismuth subcitrate


PROSTAGLANDIN ANALOGUEPROSTAGLANDIN ANALOGUE MISOPROSTOLMISOPROSTOL

MECHANISM:MECHANISM: Misoprostol is approved for use in Misoprostol is approved for use in

the prevention of the prevention of NSAID-induced gastric -induced gastric ulcers. It acts upon gastric ulcers. It acts upon gastric parietal cells, , inhibiting the secretion of inhibiting the secretion of gastric acid via via G-protein coupled receptor-mediated -mediated inhibition of inhibition of adenylate cyclase, which leads , which leads to decreased intracellular to decreased intracellular cyclic AMP levels levels and decreased and decreased proton pump activity at the activity at the apical surface of the parietal cell surface of the parietal cell


MISOPROSTOLMISOPROSTOL► Side effectsSide effects Diarrhea is one of the most common Diarrhea is one of the most common side side

effects effects reported after using Misoprostol.reported after using Misoprostol. Other common side effects include: abdominal Other common side effects include: abdominal

pain, nausea, flatulence, headache, dyspepsia, pain, nausea, flatulence, headache, dyspepsia, vomiting, and constipation.vomiting, and constipation.

► contraindicationcontraindication Misoprostol should not be taken by pregnant Misoprostol should not be taken by pregnant

women to reduce the risk of NSAID-induced women to reduce the risk of NSAID-induced gastric ulcers because it increases uterine tone gastric ulcers because it increases uterine tone and contractions in pregnancy which may cause and contractions in pregnancy which may cause partial or complete abortions, and because its partial or complete abortions, and because its use in pregnancy has been associated with birth use in pregnancy has been associated with birth defects. defects. Visit :www.bpharmstuf.com

ANTACIDSANTACIDS

► Antiacids can raise gastric pH from 1 to Antiacids can raise gastric pH from 1 to 3.5. Their duration of action is determined 3.5. Their duration of action is determined by their acid-combining ability and the by their acid-combining ability and the length of stay in the stomachlength of stay in the stomach

► The potency of an antacid is generally The potency of an antacid is generally expressed in terms of its acid neutralizing expressed in terms of its acid neutralizing capacity, which is defined as number of capacity, which is defined as number of mEq of 1N HCl that brought to pH 3.5 in 15 mEq of 1N HCl that brought to pH 3.5 in 15 min by unit dose of the acid preparation. min by unit dose of the acid preparation.


Sodium bicarbonateSodium bicarbonate It is water soluble, acts It is water soluble, acts

instantaneously, but duration of action is instantaneously, but duration of action is short. It is a potent neutralizer(1g-12mEq HCl), short. It is a potent neutralizer(1g-12mEq HCl), pH may raises above 7.pH may raises above 7.Adverse reactionsAdverse reactions

It causes systemic alkalosis, gastric distention, It causes systemic alkalosis, gastric distention, rebound acidity and milk-alkali syndromerebound acidity and milk-alkali syndrome

Drug interactionsDrug interactions Sodium containing antacids reduce Sodium containing antacids reduce

antihypertensive drug effectantihypertensive drug effect UsesUses It is restricted to casual treatment of heartburn It is restricted to casual treatment of heartburn

and to treat acidosis and to treat acidosis Visit :www.bpharmstuf.com

ULCER PROTECTIVESULCER PROTECTIVESSUCRALFATESUCRALFATE MCHANISM:MCHANISM:► Sucralfate is a locally acting Sucralfate is a locally acting substance that in that in

an acidic environment (pH < 4), reacts with an acidic environment (pH < 4), reacts with hydrochloric acid in the in the stomach to form a to form a cross-linking, cross-linking, viscous, paste-like material , paste-like material capable of acting as an capable of acting as an acid buffer for as long for as long as 6 to 8 hours after a single as 6 to 8 hours after a single dose. It also . It also attaches to attaches to proteins on the surface of ulcers, on the surface of ulcers, such as such as albumin and and fibrinogen, to form stable , to form stable insoluble complexes. These complexes serve as complexes. These complexes serve as protective barriers at the ulcer surface, protective barriers at the ulcer surface, preventing further damage from preventing further damage from acid, pepsin, , pepsin, and bile. and bile.


SUCRALFATESUCRALFATE► Side effectsSide effects The most common side effects seen are The most common side effects seen are

constipation. Less commonly reported constipation. Less commonly reported include flatulence, cephalalgia (headache), include flatulence, cephalalgia (headache), xerostomia (dry mouth). xerostomia (dry mouth).

► Drug interactionsDrug interactions Sucralfate interferes with the absorption Sucralfate interferes with the absorption

of tetracyclines, flouroquinolones, of tetracyclines, flouroquinolones, cimetidine, phenytion and digoxin. cimetidine, phenytion and digoxin. Antacids reduce the efficacy of sucralfateAntacids reduce the efficacy of sucralfate


SUCRALFATESUCRALFATE

►DOSE: DOSE: 11 gm taken for 1 hrgm taken for 1 hr

► USES: USES:

It is used in treatment of It is used in treatment of

Gastritis, Gastritis,

Stress ulcers.Stress ulcers.


ANTI H.PYLORI DRUGSANTI H.PYLORI DRUGS Anti microbials that have been found clinically Anti microbials that have been found clinically

effective against H.pylori are: amoxicillin, effective against H.pylori are: amoxicillin, clarithromycin, tetracycline and metronidazole.clarithromycin, tetracycline and metronidazole.

Bismuth active against H.pylori and resistance Bismuth active against H.pylori and resistance not develop to it.not develop to it.

A combination regimen is preferred, using A combination regimen is preferred, using gastric acid inhibitors and antibiotics. Two gastric acid inhibitors and antibiotics. Two examples are: examples are:

A proton pump inhibitor or H2 blocker + A proton pump inhibitor or H2 blocker + amoxicillin + clarithromycin or metronidazole amoxicillin + clarithromycin or metronidazole

A proton pump inhibitor + bismuth subsal + A proton pump inhibitor + bismuth subsal + tetracycline + metronidazoletetracycline + metronidazole


REFERENCESREFERENCES

►Medical pharmacology by tripathiMedical pharmacology by tripathi►Pharmacology by salil.k.bhattacharyaPharmacology by salil.k.bhattacharya►Pharmacology by H.P rang, M.M dale & Pharmacology by H.P rang, M.M dale &

J.M Ritter J.M Ritter


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Antiulcer Drugs