Acetazolamide
Carbonic anhydrase inhibitor
Generic Name
Carbonic anhydrase inhibitor
Mechanism
- Carbonic anhydrase inhibitor (enzyme‑specific inhibition of CA II in proximal tubules).
- ↓Formation of hydrogen ions → ↓Na⁺, HCO₃⁻ reabsorption → increased urinary pH, volume, and chloride excretion.
- Reduces aqueous humor production by blocking CO₂ ↔ H₂O ↔ H⁺ + HCO₃⁻ conversion in ciliary epithelium, lowering intra‑ocular pressure.
- Decreases cerebrospinal fluid (CSF) production by the choroid plexus via the same enzymatic blockade.
- Increases renal ammoniagenesis → enhanced acid excretion, promoting metabolic acidosis that drives bicarbonate loss.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | ~70 % oral bioavailability; peak plasma 1–2 h |
| Distribution | Volume of distribution ~70 ml/kg; crosses placenta, breast milk |
| Metabolism | Minimal hepatic metabolism; primarily excreted unchanged |
| Excretion | Renal (≈90 %) via glomerular filtration; 10 % biliary |
| Half‑life | 2–3 h (single dose); ~4 h after steady state |
| Protein binding | 17 % (low) – facilitates CNS effects |
Key point: Renal function prolongs elimination; adjust dosing in CKD.
Indications
- Glaucoma – acute angle‑closure, chronic, and refractory glaucoma.
- Idiopathic intracranial hypertension (pseudotumor cerebri).
- High‑altitude cerebral/ pulmonary edema prophylaxis and treatment.
- Epilepsy adjunctive therapy – short‑term for refractory seizures at high cost‑effectiveness.
- Pre‑operative diuretic – induces mild metabolic acidosis to blunt anesthetic requirements.
- Miscellaneous – reduces intraoperative blood loss, treats nocturnal leg cramps (off‑label).
Contraindications
- Absolute:
- Known hypersensitivity to sulfa drugs, acetazolamide or other sulfonamides.
- Severe renal impairment (CrCl < 15 ml/min).
- Relative:
- Anion gap metabolic acidosis, gout, hyperuricemia, hyperphosphatemia.
- Pregnancy (category B) – use only if benefits outweigh risks.
- Severe hepatic dysfunction; caution in elderly and those on diuretics.
- Warnings:
- Monitor for paradoxical hyperchloremia and renal tubular acidosis (type 2).
- Avoid concurrent potassium‑wasting diuretics (loop, thiazide) to prevent hypokalemia.
Dosing
| Indication | Dose | Route | Frequency |
| Acute angle‑closure glaucoma | 10 mg/mL (1 mL) topical | Eye drop | Instill until IOP lowered (≤ 2×/day) |
| Chronic glaucoma | 1 mg/kg/d (max 200 mg) | Oral | BID |
| Idiopathic intracranial hypertension | 125 mg × 2/d | Oral | BID |
| High‑altitude pulmonary edema | 250–500 mg d | Oral | Daily (pre‑flight; may increase). |
| High‑altitude cerebral edema | 500 mg nightly | Oral | Once nightly |
| Epilepsy adjunctive | 125 mg × 2/d | Oral | BID (max 750 mg/d) |
| Pre‑operative diuretic | 200 mg | Oral | 30–60 min pre‑op |
• Adjust for renal impairment: Reduce daily dose by 50 % if CrCl 30–49 ml/min; avoid if < 15 ml/min.
• Titration: Increase by 125 mg increments if therapeutic response inadequate, observe for drowsiness, paresthesia, or metabolic acidosis.
Adverse Effects
| Symptom | Frequency | Notes |
| Taste disturbance, metallic taste, paresthesias | Common | Anticipate; counsel patient |
| GI upset, nausea, dysuria | Common | Take with food |
| Hypokalemia, hyponatremia, metabolic acidosis | Common | Monitor electrolytes |
| Drowsiness, ataxia, dizziness | Common | Caution with driving |
| Hypersensitivity rash, Stevens–Johnson syndrome | Rare | Immediate discontinuation |
| Hyperuricemia → gout | Rare | Prophylactic allopurinol if needed |
| Renal tubular acidosis (type 2) | Rare | Check anion gap, Urine pH |
| Elevated serum creatinine in renal disease | Rare | Dose adjust |
Monitoring
| Parameter | Target/Reference | Frequency |
| Serum electrolytes (K⁺, Na⁺, Cl⁻, HCO₃⁻) | K⁺ ≥ 3.0 mEq/L; HCO₃⁻ ≥ 22 mEq/L | Baseline, 1–2 weeks, then every 4–6 weeks |
| Urine pH | pH > 5.5 (if metabolic acidosis suspected) | As indicated |
| Complete metabolic panel | N/A | 2–4 weeks after therapy initiation |
| Intra‑ocular pressure | IOP ≤ 21 mm Hg | Weekly until stabilized, then monthly |
| Renal function (CrCl) | CrCl ≥ 30 ml/min | Baseline, 4–6 weeks post‑initiation |
| Gout screening (uric acid) | Normal | Before starting if risk factors present |
Clinical Pearls
- “Bite the bullet, not the bottle” – Acetazolamide’s diuresis is mild but cumulative; avoid overlapping with loop or thiazide diuretics unless you can monitor K⁺ closely.
- High‑altitude hikers: Start 2 days before ascent; 500 mg nightly prevents cerebral edema, while a 250–500 mg daily dose mitigates pulmonary edema.
- Glaucoma patients on prostaglandin analogs: Add acetazolamide for refractory cases; monitor for metabolic acidosis, but combination is synergistic for lowering IOP.
- Pregnancy: Category B – low placental transfer, but use only if the ocular or neurological benefit outweighs any theoretical risk.
- Sulfadiazine‑like metabolites: In sulfa‑allergic patients, still contraindicated due to cross‑reactivity; use caution.
- Electrolyte repletion: Give potassium chloride or oral potassium supplement 30–60 min before dose to blunt hypokalemia, particularly in older adults.
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• Key take‑away: Acetazolamide is a versatile, fast‑acting carbonic anhydrase inhibitor with broad indications—from glaucoma and idiopathic intracranial hypertension to altitude sickness prophylaxis. Master its dose‑titration, electrolyte monitoring, and contraindication profile to maximize efficacy while avoiding the common pitfalls.