Upper GI Pharm

Question 1

H+/K+ ATPase Pump Inhibitors

Therapeutic use:

MOA:

Metabolism:

SE:

Answer 1

Omeprazole, esomeprazole, lansoprazole
Therapeutic use: gastric and duodenal ulcers, GERD, pathological hypersecretory conditions (ZE).
MOA: Absorbed into systemic circulation, diffuse into the gastric parietal cells, secreted into acidic secretory canaliculi and catalized to a sulfonamide. Sulfonamide is trapped here and binds with cysteine sulfhydryl groups in the ATP-ase. IRREVERISBLY inactivates pump. KEY: converted by acid! Often enteric-coated, combined with sodium bicarb to prevent degradation of PPI in gastric lumen.
Metabolism: hepatic P450
SE: few. Chronic—increased risk of bone fracture and increased susceptibility of some infxn.

Question 2

Histamine H2 Receptor Antagonists

Answer 2

Comp, reversible. Decreases basal (nocturnal secretion).

Metabolism: renal secretion
Cimetidine: inhibits cytochrome P450
Ranitidine (zantac)
Tolerance—due to increased gastrin secretion.

Question 3

Prostaglandins

Answer 3

NSAID blocks PG production
Misoprostol: methyl PGE1 derivative to prevent NSAID induced mucosal injury.
SE: abd cramping and diarrhea, abortifacient, can worsen IBD.

Question 4

Sucralfate

Answer 4

Sucrose sulfate + Al(OH)3
In stomach acid forms polymer gel in acid environment. Adheres to epithelial cells and ulcer craters. Protects ulcer from pepsin hydrolysis. Can stimulate local PG and epidermal GF.
SE: constipation, inhibit absorption of some drugs.

Question 5

Name the antacids and their side effects

Answer 5

Neturalize gastric HCL
Al(OH)3 Aluminum hydroxide: constipation
Mg(OH)2 Magnesium hydroxide: diarrhea
NaHCO3 Sodium bicarb = rapidly clear and short duration à not used here.
CaCO3 (calcium carbonate) = rapid onset, longer duration, also calcium supplement.

Sodium bicarb and carbonates –> CO2 gas

Drug interactions: can change drug abs/elimination. Al+Mg can bind some drugs. Avoid use of antacids and drugs that require systemic absorption.
Simethiocone (surfactant): common additive to antacids.

Question 6

Bismuth subsalicylate (peptobismol)

Answer 6

Trivalent bismuth and salicylate (à Reye’s syndrome) in Mg Al silicate clay. Possibly binds to ulcer and promote mucin and bicarb production.
SE: black stools, black tongue.
Salicylate absorbed systemically à Reye’s syndrome

Question 7

Antibiotics for H pylori

Answer 7

Single therapy does not work
Metronidazole, clarithromycin, amoxicillin, tetracycline

Question 8

Ulcer Tx strategies

Answer 8

H pylori +: reduce acid and eradicate H pylori
NSAID-related: reduce acid, replace PG
None of the above: reduce acid
GERD: depends on level of severity

Question 9

Scopolamine

Answer 9

(anticholinergic): Ach (++++), motion sickness (post-op nausea)

Question 10

Dimenhydrinate

Answer 10

(antihistamine H1): Ach (++), Histamine (++++), target vestibular affarents and brainstem

Question 11

Granisetron and ondasetron

Answer 11

(anti-serotonins 5HT3): serotonin (++++), Site of action = CNS and peripheral nerves. Used for chemo, irradiation-related nausea.

Question 12

Metoclopramide

Answer 12

(benzamide): dopamine (+++), serotonin (++)

Question 13

Prochlorperazine

Answer 13

(phenothiazine): dopamine (++++), Ach (++), histamine (++)

For general use. Site of action: CTZ. SE: restlessness

Question 14

Dronabinol

Answer 14

(tetrahydrocannabinol): MOA = CB1 receptor agonist, prophylaxis of refractory, chemotherapy-induced vomiting. SE = marijuana.

Question 15

Dexamethasone

Answer 15

(steroid): MOA = maybe associated with anti-inflammatory effects. Used with other anti-emitics for chemo.

Question 16

Aprepitant:

Answer 16

substance P, NK1 receptor antagonists. For acute and delayed chemo nausea and vomiting. Liver metabolized CYP 3A4. Usually given with 5HT3 antagonists and corticosteroid. SE = fatigue, nausea, constipation, hiccups.

Question 17

Prokinetics:

Metoclopramide

Erythromycin

Answer 17

• *Metoclopramide**: complex interactions—D2 antagonists and 5HT receptors. Antiemetic effect is at the CTZ. Enhanced gastric emptying by enhacing ACH release in myenteric plexus. Tx for diabetic gastropareisis and GERD. SE = drowsiness, dystonia, dystonia reactions.
• *Erythromycin**: Similar to motilin, tx for diabetic gastroparesis. SE = cramping.