Mechanism of Action of Acetazolamide

Introduction

Acetazolamide is a carbonic anhydrase inhibitor with diuretic, antiglaucoma, anticonvulsant, and altitude sickness applications. It reduces bicarbonate reabsorption in the kidney, lowers intraocular and intracranial pressures, and helps correct metabolic alkalosis.

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Step-by-Step Mechanism of Action

1. Inhibition of carbonic anhydrase in proximal tubule
   Blocks conversion of CO₂ and H₂O to H⁺ and HCO₃⁻, reducing bicarbonate reabsorption and causing bicarbonate diuresis.tandfonline.com+8reference.medscape.com+8youtube.com+8reference.medscape.com+6en.wikipedia.org+6youtube.com+6
2. Increased urinary excretion of bicarbonate, sodium, potassium, and water
   Leads to metabolic acidosis, mild diuresis, and changes in electrolyte balance.en.wikipedia.org+2reference.medscape.com+2synapse.patsnap.com+2
3. Reduced aqueous humor and cerebrospinal fluid formation
   Inhibition in eye and choroid plexus reduces IOP and ICP.derangedphysiology.com+15en.wikipedia.org+15pubmed.ncbi.nlm.nih.gov+15
4. Metabolic acidosis stimulates ventilation
   Useful in altitude sickness by counteracting respiratory alkalosis.inchem.org+10en.wikipedia.org+10ccforum.biomedcentral.com+10
5. Anticonvulsant activity via CNS pH modulation and ASIC effects
   Alters neuronal excitability through acid-sensing ion channels.en.wikipedia.org+15ncbi.nlm.nih.gov+15pmc.ncbi.nlm.nih.gov+15

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Pharmacokinetic Parameters

Parameter	Value
Bioavailability	Well absorbed
Time to peak plasma	~1–4 hours
Protein Binding	~70–90%derangedphysiology.com+15en.wikipedia.org+15reference.medscape.com+15ccforum.biomedcentral.com+3reference.medscape.com+3derangedphysiology.com+3
Metabolism	None (excreted unchanged)
Elimination half-life	~4–9 hours (up to 60 h in renal failure)
Excretion	~90% renal

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Clinical Uses

• Glaucoma (reducing aqueous humor production)
• Edema and heart failure (weak diuresis)
• Seizure management (adjunct)
• Acute mountain sickness prevention/treatment
• Idiopathic intracranial hypertension
• Alkalinization of urine

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Adverse Effects

• Metabolic acidosis, hypokalemia
• Paresthesia, taste alterations
• GI upset, nephrolithiasis
• Rare: Stevens–Johnson syndrome
• Contraindicated in cirrhosis due to encephalopathy risken.wikipedia.org+4en.wikipedia.org+4synapse.patsnap.com+4tandfonline.com+11ncbi.nlm.nih.gov+11synapse.patsnap.com+11it.wikipedia.org+5en.wikipedia.org+5pediatriconcall.com+5

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Comparative Analysis

Compared to other diuretics, acetazolamide is a weak diuretic but uniquely effective for metabolic alkalosis, altitude sickness, glaucoma, and increased intracranial pressure due to its action on carbonic anhydrase across tissues.

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MCQs (15 questions)

1. Acetazolamide acts by inhibiting which enzyme?
a) Na⁺/K⁺-ATPase
b) Carbonic anhydrase
c) 5-HT₃ receptor
d) ACE
Answer: b) Carbonic anhydrase

2. Site of primary action in kidney?
a) Distal tubule
b) Proximal tubule
c) Loop of Henle
d) Collecting duct
Answer: b) Proximal tubule

3. Result of acetazolamide in blood?
a) Alkalosis
b) Acidosis
c) Neutral pH
d) No change
Answer: b) Acidosis

4. Use in altitude sickness due to?
a) Volume expansion
b) Ventilation stimulation
c) Sedation
d) Hypotension
Answer: b) Ventilation stimulation

5. Not a use of acetazolamide?
a) Glaucoma
b) Heart failure mainstay
c) Mountain sickness
d) Idiopathic intracranial hypertension
Answer: b) Heart failure mainstay

6. Metabolism status?
a) Extensively metabolized
b) Not metabolized
c) Via CYP enzymes
d) Only in liver
Answer: b) Not metabolized

7. A common adverse effect?
a) Hypokalemia
b) Hyperglycemia
c) Thrombocytopenia
d) Bradycardia
Answer: a) Hypokalemia

8. Effect on cerebral fluid?
a) Increases
b) No effect
c) Decreases
d) Fluctuates
Answer: c) Decreases

9. Protein binding approximate?
a) 10%
b) 50%
c) 80%
d) 100%
Answer: c) 80%

10. Half-life in renal failure may be:
a) Shorter
b) Unchanged
c) Extended significantly
d) None
Answer: c) Extended significantly

11. Use in glaucoma is due to:
a) Increased aqueous production
b) Decreased production
c) Increased outflow
d) No ocular effect
Answer: b) Decreased production

12. Acid-sensing ion channel modulation contributes to:
a) Diuresis
b) Antihypertensive effect
c) Anticonvulsant activity
d) Hypoglycemia
Answer: c) Anticonvulsant activity

13. Mechanism of urine alkalinization?
a) H⁺ retention
b) HCO₃⁻ retention
c) HCO₃⁻ excretion
d) Na⁺ retention
Answer: c) HCO₃⁻ excretion

14. It is contraindicated in:
a) Asthma
b) Cirrhosis
c) Hypertension
d) Diabetes
Answer: b) Cirrhosis

15. Typical dose for altitude prevention?
a) 10 mg daily
b) 125 mg twice daily
c) 1 g weekly
d) IV only
Answer: b) 125 mg twice daily

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FAQs

1. Does acetazolamide cause profound diuresis?
No, it’s a mild diuretic mainly affecting bicarbonate handling.

2. Should labs be monitored during use?
Yes—electrolytes, acid-base status, and renal function are important.

3. Is it safe in pregnancy?
Not typically—category C risk; used only if benefits outweigh risks.

4. Can it worsen metabolic acidosis in COPD?
Potentially, due to reduced bicarbonate buffering.

5. Why is it used in glaucoma?
It decreases aqueous humor production via enzyme inhibition in the eye.

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References

• Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th Edition
• KD Tripathi. Essentials of Medical Pharmacology, 8th Edition
• DrugBank: Acetazolamide pharmacology
• StatPearls: Acetazolamide mechanism
• PubMed: Anticonvulsant mechanisms of acetazolamide
• PubMed: Half-life and pharmacokinetics
• ScienceDirect: Acetazolamide half-life in renal failure
• PubMed Central: respiratory stimulation effects

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