⚠️ Adverse reactions: Sulphonamides carry a risk of Stevens–Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anaemia.
Monitor closely for rash, cytopenia, or hepatic dysfunction, particularly in long-term use.
- Acetazolamide is a carbonic anhydrase inhibitor and a sulphonamide derivative.
- It acts primarily in the proximal renal tubule, inhibiting bicarbonate reabsorption and promoting mild diuresis with urinary alkalinisation.
- Also reduces aqueous humour formation in the eye and cerebrospinal fluid (CSF) secretion in the choroid plexus.
⚙️ Mechanism of Action
- Inhibition of carbonic anhydrase decreases the conversion of carbonic acid to CO₂ and water.
- This leads to loss of bicarbonate (HCO₃⁻) in urine, metabolic acidosis, and mild diuresis.
- In the eye, reduced aqueous humour lowers intraocular pressure — useful in glaucoma.
- At altitude, it induces a mild metabolic acidosis, stimulating ventilation and improving oxygenation.
🎯 Indications & Dosing
- Primary open-angle glaucoma
- Altitude sickness prophylaxis
- Raised intracranial pressure (ICP) / idiopathic intracranial hypertension
- Epilepsy (especially absence/petit mal, adjunctive use)
- Congestive cardiac failure (for diuresis when resistant to loop diuretics)
💊 Common Adult Doses (Check BNF for confirmation)
| Indication | Dose | Frequency | Route |
|---|
| Glaucoma | 250–500 mg/day | Divided doses | PO |
| Altitude sickness | 125–250 mg | BD | PO (start 24–48h before ascent) |
| Epilepsy | 250 mg–1 g/day | Divided doses | PO |
| Idiopathic intracranial hypertension | 250 mg–1 g/day | Divided doses | PO |
⚠️ Contraindications
- Known sulphonamide allergy
- Metabolic or respiratory acidosis
- Severe hepatic impairment (risk of hepatic encephalopathy)
- Hyponatraemia or hypokalaemia
- Addison’s disease or marked adrenocortical insufficiency
💥 Side Effects
- Paraesthesia (tingling in extremities), fatigue, drowsiness
- Loss of appetite, nausea, or taste disturbance
- Polyuria, thirst, metabolic acidosis
- Depression, irritability, or confusion
- Extravasation if given IV → skin necrosis
- Rare: bone marrow suppression, hypersensitivity rash, hepatic dysfunction
🔄 Interactions
- May increase plasma levels of carbamazepine.
- Enhances cardiotoxicity of flecainide, lidocaine, digoxin, and disopyramide.
- Reduces lithium levels (due to enhanced renal clearance).
- Potentiates acidosis with other carbonic anhydrase inhibitors or high-dose salicylates.
🧠 Teaching Point
Acetazolamide illustrates how renal physiology links to multiple systems: by reducing bicarbonate reabsorption, it alters CSF and aqueous humour dynamics as well as systemic acid–base balance.
Its effect on ventilation in altitude sickness is due to a mild metabolic acidosis driving compensatory hyperventilation — a neat physiological feedback mechanism to improve oxygenation at altitude.
📚 References
