Drugs Used in Gastrointestinal Diseases Final

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DRUGS USED IN GASTROINTESTINAL DISEASES

Dewi Selvina Rosdiana


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Outline Drugs used in acid peptic diseases Prokinetic agent Antiemetic

Antidiarrheals Laxatives

Antispasmodic Drug used for miscellaneous GI disorder


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DRUG USED IN ACIDPEPTIC DISEASE Acid neutralizing agents

Acid production inhibitorH2 antagonistProton-pump inhibitors

Mucosal protective agents Other acid suppressant


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Schematic model for physiologic control of hydrogen ion (acid)secretion by the parietal cells of the gastric fundic glands


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Acid neutralizing

agents:

Antacids

Combination of Al(OH) 3, Mg(OH) 2, CaCO 3(+simethicone)

Pharmacodynamics:y Form salt and watery Promote mucosal defense by stimulation of PG

production

Drug interaction:y Inhibit absorption of digoxin, phenytoin,

cimetidine, fluoroquinoloney Some Al can be absorbed


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Acid neutralizing

agents:

Antacids


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H2 receptor antagonistsCimetidine, ranitidine, nizatidine, famotidine

Pharmacodynamic:y Reduce acid secretion in 2 ways: competitive

inhibition H2 receptor & modulate PCsresponse to gastrin & Ach

y Reduce 90% (at night) and 60-80% (daytime)


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H2 receptor antagonistsPharmacokinetic:

y rapidly absorbed in intestinal lumeny Undergo 1 st pass metabolism F = 50%y T

1/2: 1-4 hrs, and d.o.a depend on dose, 10

hrs in recommended dosey Elimination: hepatic metab., glomerular

filtration filtration & renal tubular secretiony Cross the placenta, secreted into breast milk


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H2

receptor antagonistsSafety:

Extremely safe

SE: diarrhea, constipation, headache, fatigue, myalgia Gynaecomastia

Blood dyscrasi Avoid from pregnant and nursing women

Drug interaction:

cimetidine prolong half-lives drugs that are substrate forCYP: warfarin, theophylline, phenitoin, lidocaine, quinidine,b-blockers, Ca-channel blockers, benzodiazepines

Compete with procainamide for renal tubular secretion


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H2 receptor antagonists


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Proton pump inhibitorsOmeprazole, esomeprazole, lansoprazole,

pantoprazole, rabeprazolePharmacodynamic:

y Protonated & concentrated in PC canaliculiy The reactive cation binds covalently with H/K

ATPasey Reduce 80-95%, needs 3-4 days to return


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Proton pump inhibitorsPharmacokinetic: absorbed in intestinal lumen

(available in enteric coated)y An acid-labile lipophylic prodrug: need acid

environment to be activated easily diffuseinto acidified compartment (PC canaliculi)

y To be administered 1 hour before mealy Highly protein boundy

Undergo 1st

pass & hepatic metabolismy T 1/2 : 1,5 hr but acid inhibition last up to 24 hry No renal elimination


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Proton pump inhibitorsSafety:

Extremely safeSE: due to highly reduction acid Reduction in cyanocobalamin absorption Food-bound minerals (?) Increase risk of enteric infections

Drug interaction Alter absorption of certain drugs


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Proton pump inhibitors


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Mucosal protective agentsSucralfate : A complex of sucrose salt + sulfated AlOH

forms a paste that selectively cover ulcers/erosionsPharmacokinetic:

y Almost unabsorbedy Breaking down into sucrose sulfate & Al salt

Pharmacodynamic:y Forming physical barrier so that prevent further caustic

damage stimulate mucosal PG & HCO3 secretiony Enhancing mucosal repair

Drug interaction:y Inhibit absorption of digoxin, phenytoin, cimetidine,

fluoroquinoloney

Some Al can be absorbed


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Bismuth compoundsPharmacodynamic: = sucralfate

Stimulate PG, mucus, bicarbonat secretionProstaglandin analog: misoprostolA methyl analog of PGE 1Pharmacokinetic:

y T 1/2 : 30 mnts 3-4 times daily

Pharmacodynamic: stimulates mucus and bicarbonatsecretionSE: diarrhea, abdominal cramp (10-20%), stimulate

uterine contraction

Mucosal defense enhancing agents


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Mechanism of action of drug used in acid peptic disease


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PROKINETIC AGENTSAgents that enhance coordinated GI motility and transitsmaterial in the GI tract Cholinomimetic

Bethanechol Neostigmin methylsulfate

Dopamine receptor antagonist Metoclopramide domperidon

Serotonin (5-HT 4) receptor agonist Cisapride, prucalopride

Motilin agonist Macrolides: erythromycin


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PROKINETIC AGENTS

Side effects: Metoclopramide

Extrapyramidal effect Elevated prolactin level galactorrhea,

gynaecomastia, menstrual disorder methaemoglobinemia

Domperidone

No extrapyramidal effect Cisaprid Fatal cardiac arrythmia (occasionally) torsades

de pointes due to induced EAD


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Therapeutic use: GERD Impaired gastric emptying

Postvagotomy

Diabetic gastroparesis NGT-ed patients Dyspepsia syndrome (non-ulcers)

Antiemetic Persistent hiccup (metoclopramide)

PROKINETIC AGENTS


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LAXATIVES (cathartics)1. Stimulant laxatives:

y Castor oily Diphenylmethane derivatives: bisacodyly Anthraquinone derivatives: Aloe, senna, cascara

2. Bulk forming laxatives:y Natural plant: bran, psyllium, methylcellulosey Synthetic fibers: calcium polycarbophil

3. Stool softener:y docusatey mineral oily

glycerin supp4. Osmotic laxatives:y saline laxatives: magnesium citrate, sodium phosphatey unabsorbable sugars: sorbitol, lactulose


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Mechanism of action of laxatives


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ANTIEMETIC

1. Serotonin (5-HT3) receptors antagonist

Ondansetron, granisetron, ramosetron,palanosetron, dolasetron

2. Dopamine antagonist: Metoklopramide,domperidon

3. H1-antagonist : Cyclizine, Promethazine,prochlorperazine, CPZ

4. Antikolinergics: Scopolamine5. Cannabioid antagonist: Dronabinol


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ANTIDIARRHEA

1. Opioid agonist2. Colloidal bismuth compound3. Kaolin (hydrated Mg-Al silicate) & pectin

(indigestible KH)4. Bile salt-binding resin5. Octreotide


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antidiarePharmacodynamic Side effects

Opioid(Loperamide,Diphenoxylate)

Inhibit presynaptic cholinergicnerve, reduce peristaltic activity

Increase transit timeDecrease mass colonic

movements

constipation, cramps, drowsiness, paralytic ileus, abdominal bloating.

Diphenoxylate, but not loperamide, produce euphoria dan respiratory depression

Colloidal bismuth compound

direct antimicrobial effects and binds enterotoxins

Dark stools, black staining of the tounge

Kaolin & pectin adsorbents of bacterial toxins and fluid, thereby decreasing stool

liquidity and number.

Have no significant adverse effect except constipation.Should not be taken within 2 hours of other medication

Bile salt binding resin(Cholestiramine,Colestipol, colesevalam)

binds bile salts and increases fecal excretion of bile acids

Bloating, flatulence, constipationFat malabsorptionShould not be taken within 2 hours

of other medicationSomatostatin like (Octreotide)

reduces intestinal fluid secretion & pancreatic secretion

slows GI motility, inhibit gallbladder contraction

Steatorrhea, nausea, bloatingFatsoluble vitamin deficiencyGallstone formation, hypo/hyperglycemia


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ANTIPASMODIC1. Anticholinergic

Hyoscyamine, Dicyclomine2. Serotonin (5-HT 3) receptor antagonist

AlosetronIndication:

to prevent the pain and fecal urgency in

patient with IBStreatment of diarrhea-predominant IBS


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Drug used for miscellaneous GI disorder

1. Pancreatic enzymes: pancreatin, pancrelipase Chronic pancreatitis Malabsorption

2. Bile acids: ursodeoxycholic Gallstone dissolution

3. Antiflatulance: simethicone, herbal prep.

(antifoaming agent)


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References McQuaid KR. Drugs used in the treatment of Gastrointestinal diseases. In:

Katzung BG, Masters SB, and Trevor AJ. Basic and clinical pharmacology. 11 th ed. Singapure. McGraw Hill; 2009. p.1067 98.

Wallace JL, Sharkey KA. Pharmacotherapy of gastric acidity, peptic ulcers, and gastroesophageal reflux disease. In: Goodman & Gilmans the pharmacological basis of therapeutics. 12 th ed. New York: McGraw Hill;

2011. p. 1309 21. Wallace JL, Sharkey KA. Treatment of disorders of bowel motility and

water flux; antiemetics; agents used in biliary and pancreatic disease. In: Goodman & Gilmans the pharmacological basis of therapeutics. 12 th ed.

New York:

McGraw

Hill;

2011.

p.

1323

49. Page C, Curtis M, Walker M, Hoffman B. Integrated pharmacology. 3rd ed.

Spain. Elsevier Mosby; 2006.p.475 507


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Drugs Used in Gastrointestinal Diseases Final

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