A 48-year-old woman with peptic ulcer disease is being counselled on H₂-receptor antagonist therapy. She asks which is the most common side effect she might experience during the first few weeks of treatment. What is the most appropriate answer?

Explanation

## Most Common Side Effects of H₂-Receptor Antagonists **Key Point:** Headache and dizziness are the most frequent adverse effects of H₂ blockers, occurring in 1–3% of users, particularly in the early weeks of therapy. ### Mechanism and Incidence of Common H₂ Blocker Adverse Effects | Adverse Effect | Incidence | Mechanism | Timing | |---|---|---|---| | **Headache** | 1–3% | Central H₂ receptor blockade; exact mechanism unclear | Early, often resolves | | **Dizziness** | 1–2% | CNS penetration; more common with cimetidine | Early weeks | | Gynaecomastia | 0.3–0.5% | Androgen receptor antagonism (cimetidine) | Weeks to months | | Sexual dysfunction | 0.3–0.5% | Androgen receptor antagonism; rare with other agents | Weeks to months | | Liver injury | <0.1% | Idiosyncratic; very rare | Variable | | Thrombocytopenia | <0.1% | Immune-mediated; extremely rare | Variable | ### Why Headache/Dizziness Are Most Common 1. **Dose-dependent:** Occur more frequently at higher doses 2. **CNS penetration:** H₂ blockers cross the blood–brain barrier, especially cimetidine 3. **Early onset:** Usually appear within the first 1–2 weeks; often self-limiting 4. **Reversible:** Symptoms resolve upon dose reduction or drug discontinuation **Clinical Pearl:** Cimetidine has the highest incidence of CNS side effects (headache, confusion, dizziness) due to greater lipophilicity and CNS penetration. Ranitidine and famotidine are more selective for peripheral H₂ receptors and have lower CNS side effect rates. **High-Yield:** Endocrine and haematologic side effects (gynaecomastia, sexual dysfunction, thrombocytopenia) are rare and occur with prolonged use, not in the "first few weeks" as specified in the stem. ### Comparison of H₂ Blockers | Agent | CNS Side Effects | Endocrine Effects | Drug Interactions | |---|---|---|---| | Cimetidine | High | High (androgen antagonism) | Extensive (CYP450 inhibitor) | | Ranitidine | Low | Low | Minimal | | Famotidine | Very low | Very low | Minimal | | Nizatidine | Low | Low | Minimal | [cite:KD Tripathi 8e Ch 50]