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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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