Exam 2: Lecture X, GI System

Question 1

Drugs for GI Disorders

Answer 1

Drugs for acid-peptic disease
Drugs to promote GI motility
Antidiarrheal agents

Question 2

Drugs for acid-peptic disease

Answer 2

antacids
Mucosal Protective agents
PPI
H2 antagonists
antibiotics

Question 3

Antacids are….

Answer 3

physical agents directly reacting with protons in the lumen of stomach

Question 4

Typical Antacids

Answer 4

Sodium Bicarb - Alka Seltzer

Calcium carbo - Tums

Question 5

Most popular antacids in USA….

Answer 5

are weak bases

Mg + Al Hydroxide

Question 6

“Milk of Magnesia

Answer 6

Mg Hydroxide

strong laxative effect

Question 7

Alu-Cap, Aludrox, Gaviscon

Answer 7

Al Hydroxide

constipating effect

Question 8

Sucralfate (Al sucrose sulfate)

Answer 8

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

Question 9

Bismuth compounds:
Bismuth subsalicyte = bismuth + salicylate
Bismuth subcitrate potassium

Answer 9

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

Question 10

Misoprostol (methyl analog of PGE1)

Answer 10

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

Question 11

PPI info

Answer 11

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

Question 12

PPI drugs

Answer 12

Omeprazole (Prilosec, Zegerid)
Esomeprazole (Nexium)
Lansoprazole (Prevacid)
Dexlansoprazole (Dexilant)
Rabeprazole (Aciphex)
Pantoprazole (Protonix)

all somewhat similar structure, but different MOA. Admin as inactive prodrugs

Question 13

Omeprazole (Zegerind, Prilosec OTC)

Answer 13

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

Question 14

H2 blockers

Answer 14

Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepsid)
Nizatidine (Axid)

advent of PPI decreased use of H2 blockers

Question 15

Cimetidine (Tagamet)

Answer 15

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)

Question 16

Cimetidine (Tagamet) Toxicity

Answer 16

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

Question 17

Antibiotic for GI

Answer 17

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

Question 18

Metoclopramide (Reglan)

Answer 18

Muscarinic receptor agonist (gastroprokinetic activity)

5-HT4 agonist (gastroprokinetic activity)

D2 receptor antagonist in the CTZ (antiemetic effect)

5-HT3 antagonist (antiemetic effect)

Question 19

Metoclopramide (Reglan) - CLINICAL USE

Answer 19

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

Question 20

Metoclopramide (Reglan) - SIDE EFFECTS

Answer 20

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.

Question 21

Cisapride (Prepulsid, Propulsid)

Answer 21

5-HT4 agonist (gastroprokinetic activity)
Indirectly as a parasympathomimetic

Clinical Use
Gastroesophageal reflux disease

Side Effect
Arrhythmias!!!
Withdrawn in 2000!!! Commonly used by veterinarians.

Question 22

ANTIDIARRHEAL AGENTS

Answer 22

Opioids and opioid derivatives

Adsorbents

Agents that modify fluid and electrolyte transport

Question 23

Most effective antidiarrheal drugs….

Answer 23

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.

Question 24

Adsorbants are….

Answer 24

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

Question 25

Most important Adsorbents

Answer 25

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

Question 26

Agents that modify fluid and electrolyte transport

Answer 26

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.

Question 27

Laxatives

Answer 27

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.