Usage
Acetazolamide is prescribed for several medical conditions, including:
- Glaucoma: Reduces intraocular pressure.
- Edema: Treats fluid retention (especially in congestive heart failure).
- Epilepsy: Adjunctive therapy for certain types of seizures.
- Altitude Sickness: Prevents and treats symptoms.
- Idiopathic Intracranial Hypertension (Pseudotumor Cerebri): Lowers intracranial pressure.
- Periodic Paralysis: Prevents attacks.
- Central Sleep Apnea: Reduces episodes.
Pharmacological Classification: Carbonic anhydrase inhibitor, diuretic.
Mechanism of Action: Acetazolamide inhibits the enzyme carbonic anhydrase, which is involved in the formation of bicarbonate ions. This inhibition leads to decreased bicarbonate reabsorption in the kidneys, resulting in increased excretion of bicarbonate, sodium, water, and potassium. This diuresis is responsible for its effect in edema and glaucoma. The effect on intracranial pressure is likely related to reduced cerebrospinal fluid production. In epilepsy, the mechanism is not fully understood but may involve changes in neuronal excitability.
Alternate Names
International/Regional Variations: Diamox (common brand name used internationally)
Brand Names: Diamox, Diamox Sequels.
How It Works
Pharmacodynamics: Acetazolamide primarily acts by inhibiting carbonic anhydrase, leading to diuresis (increased urine production), reduction in intraocular pressure, and decreased cerebrospinal fluid production. It can also cause mild metabolic acidosis.
Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Minimal hepatic metabolism.
- Elimination: Primarily renal excretion (unchanged drug).
Mode of Action: Acetazolamide binds to the active site of carbonic anhydrase, preventing the enzyme from catalyzing the conversion of carbon dioxide and water into bicarbonate and hydrogen ions. This ultimately reduces bicarbonate reabsorption in the proximal tubules of the kidneys.
Receptor Binding/Enzyme Inhibition: Acetazolamide is a reversible inhibitor of carbonic anhydrase isoenzymes, particularly CA II and CA IV.
Elimination Pathways: Primarily excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Glaucoma: 250-1000 mg/day orally, in divided doses. Extended-release capsules: 500 mg twice daily.
- Edema: Initially 250-375 mg/day orally. Maintenance: Alternate days or 2 days on, 1 day off.
- Epilepsy: 250-1000 mg/day orally, in divided doses.
- Altitude Sickness: 250 mg every 8-12 hours or 500 mg extended-release once daily, starting 24-48 hours before ascent. For rapid ascents, 1000 mg/day.
Children:
- Glaucoma: 10-30 mg/kg/day orally, in divided doses (max 1000 mg/day).
- Epilepsy: 8-30 mg/kg/day orally, in divided doses (max 750 mg/day).
Special Cases:
- Elderly Patients: Use with caution due to potential for electrolyte imbalances and renal/hepatic impairment. Dose adjustments may be necessary.
- Patients with Renal Impairment: Dose reduction needed. Not recommended for severe renal disease (GFR <10 mL/min).
- Patients with Hepatic Dysfunction: Contraindicated in cirrhosis due to risk of hepatic encephalopathy. Use cautiously in less severe liver disease.
- Patients with Comorbid Conditions: Monitor closely for electrolyte imbalances, particularly in patients with diabetes or cardiovascular disease.
Clinical Use Cases
Dosing in clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations (e.g., status epilepticus, cardiac arrest) should be individualized based on patient needs and in consultation with specialists. IV administration may be used in these settings.
Dosage Adjustments
Dose modifications are necessary based on renal/hepatic function, electrolyte levels, and other patient-specific factors. Therapeutic drug monitoring may be beneficial.
Side Effects
Common Side Effects
- Paresthesias (tingling in extremities), fatigue, drowsiness, headache, nausea, vomiting, loss of appetite, metallic taste, increased urination.
Rare but Serious Side Effects
- Blood dyscrasias (e.g., aplastic anemia, agranulocytosis, thrombocytopenia), Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic encephalopathy, electrolyte disturbances (hypokalemia, hyponatremia, metabolic acidosis), kidney stones, acute myopia.
Long-Term Effects
Osteoporosis with prolonged use, renal calculi.
Adverse Drug Reactions (ADR)
Severe skin reactions, blood dyscrasias, hepatic failure, electrolyte disturbances.
Contraindications
- Hypersensitivity to acetazolamide or sulfonamides.
- Marked liver or kidney disease (especially cirrhosis).
- Adrenal gland insufficiency.
- Hyperchloremic acidosis.
- Hyponatremia or hypokalemia.
Drug Interactions
- Aspirin (increased risk of acetazolamide toxicity).
- Anticonvulsants (phenytoin, primidone): altered metabolism.
- Other diuretics (additive effects).
- Digoxin (increased digoxin levels due to hypokalemia).
- Lithium (increased lithium levels).
- Methotrexate (increased methotrexate toxicity).
- Sodium bicarbonate (increased risk of renal calculi).
- Amphetamines (decreased amphetamine effectiveness).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Teratogenic effects observed in animal studies. Use only if potential benefit outweighs risk.
- Breastfeeding: Small amounts excreted in breast milk. Generally considered compatible with breastfeeding, but caution advised. Monitor infant for potential side effects.
Drug Profile Summary
- Mechanism of Action: Carbonic anhydrase inhibitor.
- Side Effects: Paresthesias, fatigue, drowsiness, nausea, increased urination. Rarely, blood dyscrasias, Stevens-Johnson syndrome, hepatic encephalopathy.
- Contraindications: Hypersensitivity to sulfonamides, severe liver/kidney disease, adrenal insufficiency.
- Drug Interactions: Aspirin, anticonvulsants, digoxin, lithium.
- Pregnancy & Breastfeeding: Category C; use with caution. Compatible with breastfeeding but monitor infant.
- Dosage: Varies by condition. See above for details.
- Monitoring Parameters: Electrolytes (sodium, potassium, chloride, bicarbonate), renal function, liver function tests, complete blood count.
Popular Combinations
- Acetazolamide with other antiglaucoma medications (e.g., beta-blockers, prostaglandin analogs).
- Acetazolamide with other antiepileptic drugs.
Precautions
- Monitor electrolytes, renal function, and liver function.
- Caution in patients with respiratory disorders, diabetes.
- Avoid prolonged sun exposure (photosensitivity).
- May impair ability to drive or operate machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Acetazolamide?
A: Dosage varies depending on indication. See “Dosage” section above for details.
Q2: What are the common side effects of Acetazolamide?
A: Common side effects include paresthesias, fatigue, drowsiness, headache, nausea, metallic taste, increased urination.
Q3: Is Acetazolamide safe during pregnancy?
A: Acetazolamide is Pregnancy Category C. Use only if clearly needed and potential benefit outweighs risk.
Q4: Can Acetazolamide be used in patients with kidney disease?
A: Use with caution and dose adjustment in patients with mild to moderate renal impairment. Contraindicated in severe renal disease.
Q5: What are the contraindications for Acetazolamide?
A: Contraindications include hypersensitivity to sulfonamides, severe liver/kidney disease, adrenal insufficiency, and hyperchloremic acidosis.
Q6: How does Acetazolamide work in glaucoma?
A: Acetazolamide decreases the production of aqueous humor, thereby reducing intraocular pressure.
Q7: What drug interactions are important to consider with Acetazolamide?
A: Significant interactions can occur with aspirin, anticonvulsants, digoxin, and lithium, among others. Consult the drug interactions section for a detailed list.
Q8: Can I take Acetazolamide if I am breastfeeding?
A: Acetazolamide is generally considered compatible with breastfeeding, but it is important to monitor the infant for potential side effects.
Q9: How long does it take for Acetazolamide to work for altitude sickness?
A: Prophylactic administration should begin 24-48 hours before ascent to high altitude.
Q10: Can Acetazolamide be used in children?
A: Yes, but dosages are weight-based and should be carefully determined by a pediatrician.
