Exam 2: Lecture X, GI System Flashcards
Drugs for GI Disorders
Drugs for acid-peptic disease
Drugs to promote GI motility
Antidiarrheal agents
Drugs for acid-peptic disease
antacids Mucosal Protective agents PPI H2 antagonists antibiotics
Antacids are….
physical agents directly reacting with protons in the lumen of stomach
Typical Antacids
Sodium Bicarb - Alka Seltzer
Calcium carbo - Tums
Most popular antacids in USA….
are weak bases
Mg + Al Hydroxide
“Milk of Magnesia
Mg Hydroxide
strong laxative effect
Alu-Cap, Aludrox, Gaviscon
Al Hydroxide
constipating effect
Sucralfate (Al sucrose sulfate)
Poorly soluble molecule
**Creates protective coating over the ulcer
Accelerates the healing of peptic ulcers
Reduces the recurrence rate
Undergoes polymerization in the acid environment of the stomach
Polymer bind to the erosion in the stomach
**Due to poor solubility, drug has no significant systemic effect
**Mechanism of action is not clear
Sucralfate is a negatively charged small molecule
Positively charged proteins are at the base of ulcer or erosion
A physical barrier is formed
Restricts further acidic damage
Bismuth compounds:
Bismuth subsalicyte = bismuth + salicylate
Bismuth subcitrate potassium
Bismuth coats ulcers and erosions
Creates a protective layer against acids and pepsin
Stimulates mucus prostaglandins and bicarbonate secretion
Bismuth has direct antimicrobial effects
Bismuth is also used for treatment of dyspepsia and acute diarrhea
Misoprostol (methyl analog of PGE1)
Mucosal Protective Agent
Stimulates mucus and bicarbonate secretion
Enhances mucosal blood flow
Binds to prostaglandin receptors on parietal cells
Reduces histamine-stimulated cAMP production
Causes modest acid inhibition
Adverse effects: not to be used during pregnancy
PPI info
Agents introduced in 1980th
Efficacious agents
Major role – treatment of acid-peptic disorders
Proton pump inhibitors – mostly prescribed drugs
Characterized by an outstanding efficacy and safety
Rapid first-pass effect – mostly through hepatic metabolism
Short half-life
Up to 3-4 days required for acid-inhibiting potential
From pharmacokinetic perspective – ideal drugs
PPI drugs
Omeprazole (Prilosec, Zegerid) Esomeprazole (Nexium) Lansoprazole (Prevacid) Dexlansoprazole (Dexilant) Rabeprazole (Aciphex) Pantoprazole (Protonix)
all somewhat similar structure, but different MOA. Admin as inactive prodrugs
Omeprazole (Zegerind, Prilosec OTC)
prototype PPI
Useful to treat Gastric reflux, Zolligner-Ellison syndrome with a gastrin-secretin tumor
irreversibly binds proton pump, located in luminal membrane of parietal cell.
inhibition lasts for 48 hrs
H2 blockers
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepsid)
Nizatidine (Axid)
advent of PPI decreased use of H2 blockers
Cimetidine (Tagamet)
Relatively selective and have no effect upon H1 receptors
Relatively non-toxic - can be given in large doses
Main application in acid-peptic disease - especially duodenal ulcer
Accelerates healing and prevents recurrences
Recurrences may be prevented by a single bedtime dose
Also effective in healing and preventing severe gastric peptic ulcers
Very helpful in controlling acid hypersecretion
Very helpful in treatment of GI bleeding and diarrhea
May be used to treat gastroesophageal efflux disease (GERD)
Cimetidine (Tagamet) Toxicity
Relatively non-toxic
Potent inhibitor of hepatic enzymes
May reduces hepatic blood flow
Antiandrogen effect in many patients
(Newer H2 blockers do not have endocrine effects)
** Alcohol: Very serious drug interaction may occur
Antibiotic for GI
Infection with Helicobacter pylori is related to peptic ulcer
Relation exists in a large proportion of patients
Eradication of Helicobacter pylori reduces the rate of ulcer recurrence
Typically a course of tetracycline + metronidazole or amoxicillin + clarithromycin is used
Omeprazole accompanies either antibiotic regiment
Metoclopramide (Reglan)
Muscarinic receptor agonist (gastroprokinetic activity)
5-HT4 agonist (gastroprokinetic activity)
D2 receptor antagonist in the CTZ (antiemetic effect)
5-HT3 antagonist (antiemetic effect)
Metoclopramide (Reglan) - CLINICAL USE
Gastroesophageal reflux disease
Short-term treatment (4-12 weeks)
Helps with poor emptying of the stomach
Nausea and vomiting associated with radiation, cancer, and infections
Metoclopramide (Reglan) - SIDE EFFECTS
Diarrhea
Neuroleptic malignant syndrome
Tardive dyskinesia
Depression
Warning: Metoclopramide (Reglan) may be the leading cause of drug-induced movement disorders - especially, in population under 20 years or prolonged therapy.
Cisapride (Prepulsid, Propulsid)
5-HT4 agonist (gastroprokinetic activity)
Indirectly as a parasympathomimetic
Clinical Use
Gastroesophageal reflux disease
Side Effect
Arrhythmias!!!
Withdrawn in 2000!!! Commonly used by veterinarians.
ANTIDIARRHEAL AGENTS
Opioids and opioid derivatives
Adsorbents
Agents that modify fluid and electrolyte transport
Most effective antidiarrheal drugs….
opioids and opioid derivatives
Diphenoxylate – typically is formulated with atropine
Loperamide (Anti-Diarrheal, Anti-Diarrhea, Diamode ) – typically is formulated alone
Agents activate presynaptic opioid receptors in the enteric nervous system
Inhibit acetylcholine release and decrease peristalsis
Side effects:Drowsiness, Abdominal cramps, Dizziness
***Warning: Should not be given to young children or patients with severe colitis – may cause toxic megacolon.
Adsorbants are….
widely used to control diarrhea
efficacy of these is questioned
suggest they work by adsorbing intestinal toxins, microorganism and coating/protecting mucosa.
May interfere with absorption of other drugs
Most important Adsorbents
Kaolin – a type of clay found in nature
Pectin – a fiber found in fruits (since 2004, pectin is not permitted in the OTC products)
Activated attapulgite (Fowler’s Anti-Diarrhea Tablets) – a magnesium aluminum silicate found in clay
Methylcellulose - a bulk-forming laxative
Agents that modify fluid and electrolyte transport
Clinical and experimental data indicate that NSAID’s are effective in controlling diarrhea.
Aspirin and indomethacin demonstrate antidiarrheal effect, due to the inhibition of prostaglandin synthesis.
Bismuth subsalicylate (Pepto-Bismol) is used to treat traveler’s diarrhea probably due to salicylate component.
Laxatives
Bulk – forming laxatives:
Indigestible, hydrophilic colloids
Absorb water-form gel that distends the colon-> promotes peristalsis
Natural: psyllium, methylcellulose; Synthetic fibers: polycarbophil
Stool surfactant agents (Softeners): Docusate; Glycerin suppository; Mineral oil
Osmotic laxatives: Mg [OH]2 “Milk of Magnesia”
Nonabsorbable sugars: Sorbitol, Lactulose
Nonabsorbable salts: Magnesium citrate, Sodium phosphate
Balanced Polyethylene Glycol (PEG) – Balanced isotonic solution with inert, non-absorbable PEG. No significant changes in electrolytes or intravascular fluid. Safe for all patients.
