Makindo Medical Notes

💡 Key principle: Always test for and eradicate Helicobacter pylori in suspected or proven peptic ulcer disease before or alongside acid suppression. 🩺 Nizatidine is a second-generation H₂ receptor antagonist that effectively reduces gastric acid output, particularly at night, and is well tolerated with minimal drug interactions.

🧠 About

• Histamine H₂-receptor antagonist used in peptic ulcer disease (PUD) and gastro-oesophageal reflux disease (GORD).
• Acts selectively on gastric parietal cells to inhibit both basal and stimulated acid secretion.
• Similar efficacy to ranitidine and famotidine but with improved pharmacokinetic stability and lower interaction potential.
• Rapid onset of action (within 1 hour) and duration of effect up to 12 hours.

⚙️ Mechanism of Action

• Histamine released from enterochromaffin-like (ECL) cells binds to H₂ receptors on parietal cells, stimulating H⁺/K⁺-ATPase (the proton pump).
• Nizatidine competitively inhibits these receptors, reducing both basal and nocturnal gastric acid secretion.
• Also diminishes acid response to food, gastrin, and vagal stimulation.
• Peak acid suppression occurs 1–3 hours post-dose; hepatic metabolism is minimal (largely excreted unchanged in urine).

🎯 Indications

• Benign gastric or duodenal ulceration.
• Gastro-oesophageal reflux disease (GORD) and reflux oesophagitis.
• Prevention of stress ulceration in high-risk inpatients (off-label alternative to PPIs).
• Non-ulcer dyspepsia or nocturnal acid breakthrough in PPI-treated patients.

💊 Dosing (Adults)

• Benign gastric or duodenal ulceration: 300 mg once daily at bedtime for 4–8 weeks.
• Reflux oesophagitis / GORD: 150 mg twice daily or 300 mg twice daily for 12 weeks.
• Maintenance therapy: 150 mg at bedtime may be used long term in recurrent ulcer disease.

⚠️ Cautions

• Always exclude gastric malignancy in patients with ulcer symptoms or alarm features (weight loss, vomiting, dysphagia, anaemia).
• Reduce dose in renal impairment (CrCl < 50 mL/min).
• Monitor for symptom recurrence after cessation — relapse often reflects ongoing H. pylori infection or NSAID use.
• Use cautiously in hepatic disease though largely renally excreted.

🚫 Contraindications

• Known hypersensitivity to H₂ antagonists (cross-reactivity possible).
• Severe renal failure without dose adjustment.
• Use in pregnancy or breastfeeding only if benefits outweigh risks (limited data but no proven teratogenicity).

💊 Adverse Effects

• Generally mild and transient.
• Common: headache, dizziness, fatigue, nausea, constipation.
• Occasional: sweating, hyperuricaemia, rash, arthralgia.
• Rare: hepatitis, vasculitis, reversible confusion (particularly in elderly or renally impaired patients).

🔄 Interactions

• Minimal cytochrome P450 inhibition — fewer drug interactions than cimetidine or ranitidine.
• Can reduce absorption of drugs requiring an acidic environment (e.g. ketoconazole, atazanavir).
• For full interaction list, refer to the BNF entry.

🤰 Pregnancy and Breastfeeding

• Limited human data; no evidence of fetal harm in animal studies — use only if clearly needed.
• Small quantities appear in breast milk; short-term use likely safe.

🩺 Clinical Pearls

• Less potent than PPIs but acts faster — useful for acute symptom control or nocturnal acid suppression.
• Ideal in patients intolerant to PPIs or at risk of PPI-related infections (e.g. C. difficile, pneumonia).
• Combine with lifestyle measures — smoking cessation, alcohol moderation, head-of-bed elevation, avoiding late meals.
• In NSAID users, always consider gastroprotection and H. pylori eradication.

💡 Teaching Tip

• H₂ antagonists “Halt Hydrogen” — they block histamine-stimulated acid secretion but not gastrin or acetylcholine directly.
• Explain to learners that tolerance (“tachyphylaxis”) can occur with prolonged use due to receptor up-regulation.
• Contrast with PPIs: PPIs irreversibly block the proton pump, whereas H₂ blockers act reversibly upstream at the receptor level.

📚 References

• BNF: Nizatidine
• NICE CKS: Dyspepsia and Peptic Ulcer Disease (2024)
• Howden CW. Clin Ther 1991;13:77–86 — Comparative efficacy of H₂ antagonists.