GI Acid Pharmacology

Question 1

H2 Receptor Blockers - Examples and MOA

Answer 1

Cimetidine, Ranitidine, Famotidine, Nizatidine

MOA: Competitive inhibition for histamine H2 receptor on parietal cells, decreasing acid secretion stimulated by histamine

Question 2

H2 Receptor Blockers - pharmacokinetics

Answer 2

Onset of action: 1-3 hours
Duration of action: 5+ hours
half-time: 1-3 hours
Excretion - renal and hepatic

Question 3

H2 Receptor Blockers - ADRs and interactions

Answer 3

ADRs: Headache, diarrhea, dizzines, confusion, gynecomastia (cimetidine), myelosuppression

Interactions: Drugs metabolized by P450s - theophylline, phenytoin, warfarin, benzodiazepines, anti-depressants, beta-blockers

Issues with tolerance, rebound acid hypersecretion upon withdrawl (hypergastrinemia during use)

Question 4

Proton Pump Inhibitor - Examples and MOA

Answer 4

Omeprazole, Lansoprazole, Esomeprazole

MOA: Given as a prodrug that is taken in by the basolateral parietal cell, incorporated into the tubulovesicular system, activated in the acid secreting vesicle, and covalently binds the H+ ATPase at a cysteine residue, rendering its conformation inactive.

More potent than H2 Blockers

Question 5

Proton Pump Inhibitor - Pharmacokinetics

Answer 5

Distribution: 95% protein bound
Metabolism: CYP2C19, CYP3A4
Excretion: omeprazole - renal > fecal, lansoprazole - fecal > renal
Plasma Peak Time - 2 hrs
Half-life - 1-1.5 hours

Question 6

Proton Pump Inhibitor - ADRs, interactions

Answer 6

ADRs: immune/allergic type reactions

Interactions: Clopidogrel, digoxin, warfarin, H2 receptor blockers

Issues with tolerance, rebound acid hypersecretion upon withdrawl (hypergastrinemia during use)

Question 7

Consequences of Achlorhydria

Answer 7

1) Hypergastrinemia -> trophic effect on CCKa receptor, causing ECL cell hyperplasia
2) B12 malabsorption -> folate deficiency (anemia), homocysteinemia (hypercoagulability)
3) Divalent Cation Malabsorption - Ca, Mg, Fe, Zn (require acid solubilization)
4) GI overgrowth of H. pylori, C. difficle, Candida, etc (NO, lysozyme, acid are protective)
5) Effects 1,2, 4 cause inflammation of gastric mucosa –> gastric polyps
6) Metabolic bone disease (homocysteinemia + secondary hyperparathyroidism)