Histamine and Bradykinin Pharmacology · Module 3

H2 Blockers and Gastric Acid Pharmacology

Parietal cell signaling, H2 blocker comparison, and cimetidine adverse effects

H2 Receptor Signaling Cascade — Parietal Cell

Stimulus

Histamine

→

Receptor

H2 (Gs)

→

Enzyme

Adenylyl cyclase

→

Messenger

Cyclic AMP ↑

→

Effect

Proton pump activated

→

Result

Acid secretion

H2 Blocker Comparison

Drug	Potency	CYP450 Inhibition	Antiandrogenic	Notes
Cimetidine	Low	Yes — warfarin, phenytoin, theophylline	Yes — gynecomastia, impotence	First agent; rarely used now
Famotidine	Highest	None	None	Preferred agent
Ranitidine	Intermediate	Minimal	None	Withdrawn 2020 — NDMA contamination
Nizatidine	Intermediate	None	None	Similar to famotidine

Cimetidine — Unique Adverse Effects

Drug Interactions

Cytochrome P450 Inhibition

Inhibits multiple cytochrome P450 enzymes
Warfarin — elevated levels → bleeding
Phenytoin — elevated levels → toxicity
Theophylline — elevated levels → arrhythmia, seizures
Fix: switch to famotidine

Endocrine Effect

Antiandrogenic Effects

Binds androgen receptors — antagonist effect
Gynecomastia in men
Impotence / decreased libido
Reversible on discontinuation
Fix: switch to famotidine

High-Yield Rule — H2 Blockers vs Proton Pump Inhibitors

H2 blockers are reversible competitive antagonists — partial acid suppression, overcome by high histamine. Proton pump inhibitors irreversibly block the proton pump at the final common step — near-complete suppression regardless of upstream stimuli. For erosive esophagitis, Zollinger-Ellison syndrome, and Helicobacter pylori eradication: proton pump inhibitors are first-line.