MOA of Diamox

Mechanism of Action of Diamox

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Introduction

Diamox is the brand name for acetazolamide, a carbonic anhydrase inhibitor primarily used as a diuretic, antiglaucoma agent, antiepileptic adjunct, and for the prevention and treatment of acute mountain sickness. Unlike conventional diuretics, Diamox alters acid–base balance and fluid dynamics by inhibiting carbonic anhydrase in multiple tissues. Its distinctive mechanism makes it a high-yield drug in pharmacology, ophthalmology, nephrology, neurology, and clinical entrance examinations.

Mechanism of action of Diamox
Diamox pharmacology
Diamox Mechanism of Action Flowchart
Stepwise mechanism of action of Diamox

Mechanism of Action (Step-wise)

Diamox (acetazolamide) acts by inhibiting the enzyme carbonic anhydrase, leading to altered bicarbonate handling and pH changes.

Step-wise mechanism:

  1. Carbonic Anhydrase Inhibition
    Diamox inhibits carbonic anhydrase (CA), an enzyme that catalyzes the reversible conversion of carbon dioxide and water to carbonic acid.
  2. Renal Proximal Tubule Action
    In the proximal convoluted tubule, carbonic anhydrase is essential for bicarbonate (HCO₃⁻) reabsorption.
  3. Reduced Hydrogen Ion Secretion
    Inhibition of CA decreases intracellular hydrogen ion (H⁺) formation, reducing H⁺ secretion into the tubular lumen.
  4. Decreased Bicarbonate Reabsorption
    Reduced H⁺ availability prevents sodium–hydrogen exchange, leading to decreased reabsorption of sodium bicarbonate.
  5. Increased Bicarbonate Excretion
    Excess bicarbonate is excreted in urine, causing alkaline urine and mild diuresis.
  6. Metabolic Acidosis Development
    Loss of bicarbonate results in systemic metabolic acidosis.
  7. Reduced Aqueous Humor Formation
    In the eye, CA inhibition decreases bicarbonate-dependent fluid secretion, lowering intraocular pressure.
  8. Reduced Cerebrospinal Fluid (CSF) Production
    Inhibition of CA in the choroid plexus decreases CSF formation.
  9. Ventilatory Stimulation in Altitude Sickness
    Metabolic acidosis stimulates respiration, improving oxygenation at high altitude.

Pharmacokinetics

  • Absorption: Well absorbed orally
  • Distribution: Widely distributed; penetrates eye and CNS
  • Protein binding: High
  • Metabolism: Minimal hepatic metabolism
  • Elimination: Renal excretion (unchanged drug)
  • Half-life: Approximately 10–15 hours
  • Special note: Contraindicated in severe renal disease

Clinical Uses

Diamox is used in diverse clinical settings due to its multisystem effects:

  • Glaucoma (open-angle and acute angle-closure adjunct)
  • Acute mountain sickness (prophylaxis and treatment)
  • Idiopathic intracranial hypertension (pseudotumor cerebri)
  • Metabolic alkalosis
  • Adjunct therapy in epilepsy
  • Periodic paralysis (hypokalemic type)

It is not commonly used as a primary diuretic due to weak natriuretic effect.

Adverse Effects

Adverse effects are mainly related to electrolyte imbalance and acidosis:

  • Metabolic acidosis
  • Hypokalemia
  • Paresthesias (tingling of fingers and toes)
  • Renal stone formation (calcium phosphate stones)
  • Fatigue and drowsiness
  • Sulfonamide hypersensitivity reactions

Diamox should be avoided in patients with cirrhosis due to risk of hepatic encephalopathy.

Comparative Analysis (must include a table + explanation)

Comparison of Diuretic Classes

FeatureDiamox (Acetazolamide)Loop DiureticsThiazides
Primary siteProximal tubuleLoop of HenleDistal tubule
MechanismCA inhibitionNa⁺–K⁺–2Cl⁻ inhibitionNa⁺–Cl⁻ inhibition
Effect on pHMetabolic acidosisMetabolic alkalosisMetabolic alkalosis
Diuretic potencyWeakStrongModerate
Use in glaucomaYesNoNo

Explanation:
Diamox differs from loop and thiazide diuretics by producing metabolic acidosis rather than alkalosis. Its weak diuretic action limits routine use for edema, but its effects on CSF, aqueous humor, and ventilation make it clinically unique.

MCQs (10–15)

  1. Diamox inhibits which enzyme?
    a) Cyclooxygenase
    b) Carbonic anhydrase
    c) Aldosterone synthase
    d) Na⁺/K⁺-ATPase

Answer: b) Carbonic anhydrase

  1. The primary renal site of action of Diamox is the:
    a) Collecting duct
    b) Loop of Henle
    c) Distal tubule
    d) Proximal tubule

Answer: d) Proximal tubule

  1. Diamox causes which acid–base disturbance?
    a) Metabolic alkalosis
    b) Respiratory alkalosis
    c) Metabolic acidosis
    d) Respiratory acidosis

Answer: c) Metabolic acidosis

  1. Diamox is useful in glaucoma because it:
    a) Increases aqueous humor drainage
    b) Reduces aqueous humor production
    c) Dilates pupil
    d) Relaxes ciliary muscle

Answer: b) Reduces aqueous humor production

  1. Diamox is commonly used in altitude sickness to:
    a) Increase hemoglobin
    b) Reduce pulmonary edema
    c) Stimulate ventilation
    d) Cause diuresis

Answer: c) Stimulate ventilation

  1. A characteristic adverse effect of Diamox is:
    a) Hyperkalemia
    b) Hypokalemia
    c) Hypernatremia
    d) Hypercalcemia

Answer: b) Hypokalemia

  1. Diamox alkalinizes which fluid?
    a) Blood
    b) CSF
    c) Urine
    d) Intracellular fluid

Answer: c) Urine

  1. Renal stone formation with Diamox is due to:
    a) Uric acid precipitation
    b) Calcium phosphate stones
    c) Oxalate stones
    d) Cystine stones

Answer: b) Calcium phosphate stones

  1. Diamox should be avoided in patients with:
    a) Glaucoma
    b) Altitude sickness
    c) Liver cirrhosis
    d) Pseudotumor cerebri

Answer: c) Liver cirrhosis

  1. Diamox is classified as a:
    a) Loop diuretic
    b) Thiazide diuretic
    c) Carbonic anhydrase inhibitor
    d) Potassium-sparing diuretic

Answer: c) Carbonic anhydrase inhibitor

FAQs (minimum 5)

  1. What is the primary mechanism of Diamox?
    Inhibition of carbonic anhydrase leading to bicarbonate loss and metabolic acidosis.
  2. Why is Diamox effective in altitude sickness?
    It induces metabolic acidosis that stimulates ventilation.
  3. Does Diamox lower intraocular pressure?
    Yes, by reducing aqueous humor formation.
  4. Why does Diamox cause kidney stones?
    Due to alkaline urine and calcium phosphate precipitation.
  5. Is Diamox a strong diuretic?
    No, it is a weak diuretic.
  6. Can Diamox cause electrolyte imbalance?
    Yes, especially hypokalemia and metabolic acidosis.

References

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