Carbonic Anhydrase Inhibitors

Carbonic Anhydrase Inhibitors

Carbonic Anhydrase Inhibitors

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CA Inhibitors - Fizz Busters

Carbonic Anhydrase (CA) inhibitors reduce reabsorption of $HCO_3^-$ in the Proximal Convoluted Tubule (PCT).

⭐ Primary site of action: Proximal Convoluted Tubule (PCT).

  • Mechanism: Inhibit enzyme carbonic anhydrase. Reaction: $H_2O + CO_2 \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$.
  • Examples: Acetazolamide, Dorzolamide, Brinzolamide (topical for glaucoma).
  • Uses:
    • Glaucoma (↓ aqueous humor production).
    • Acute Mountain Sickness (prophylaxis & treatment).
    • Metabolic alkalosis (to induce acidosis).
    • Urinary alkalinization (e.g., drug excretion).
    • Epilepsy (adjunctive).
  • Side Effects & Contraindications:
    • Metabolic acidosis (hyperchloremic).
    • Hypokalemia.
    • Renal stones (Calcium phosphate due to alkaline urine).
    • Paresthesias.
    • Sulfa allergy.
    • Contraindication: Liver cirrhosis (↑NH4+ toxicity).
    • 📌 "ACID"-azolamide causes ACIDOSIS. Carbonic Anhydrase Inhibitors in PCT

Clinical Uses - Pressure Relief

Acetazolamide is the primary CAI used for conditions where reducing fluid pressure is beneficial.

UseRationale for Pressure Relief
Glaucoma (esp. open-angle, acute angle-closure pre-op)↓ Ciliary body aqueous humor secretion → ↓ Intraocular Pressure (IOP)
Acute Mountain Sickness (AMS)↓ CSF production by choroid plexus → ↓ Intracranial Pressure (ICP); induces metabolic acidosis, stimulating medullary respiratory center
Idiopathic Intracranial Hypertension (IIH) / Pseudotumor Cerebri↓ CSF production → ↓ ICP; often used with weight loss
CSF Leakage (adjunctive, post-traumatic/surgical)↓ CSF production rate, potentially aiding spontaneous closure
  • A - Altitude sickness
  • C - CSF leakage
  • E - Epilepsy (adjunctive)
  • T - To alkalinize urine
  • A - Alkalosis (metabolic)
  • Z - 'z'Glaucoma

⭐ Acetazolamide is the drug of choice for prophylaxis and treatment of Acute Mountain Sickness (AMS). Prophylactic dose: 125-250 mg BD, started 24-48h before ascent.

Adverse Profile - Watch Outs!

  • Common Adverse Effects:
    • Metabolic Acidosis: Hyperchloremic, non-anion gap type.
    • Hypokalemia: Significant $K^+$ wasting can occur.
    • Hypersensitivity Reactions: Common due to sulfonamide structure (Sulfa allergy).
    • Renal Stones: Calcium phosphate stones, from ↑urinary pH and ↑phosphate excretion.
    • CNS Effects: Paresthesias, drowsiness, fatigue.
    • Hyperammonemia: Particularly in patients with pre-existing liver disease.
    • Taste Disturbances: Metallic taste (especially with acetazolamide).
    • 📌 Mnemonic: "ACIDotic HHHypoK" - Metabolic ACIDOSIS, Hypersensitivity (Sulfa), Hypokalemia, Hyperchloremia.
  • Contraindications & Cautions:
    • Known hypersensitivity to sulfonamides (Sulfa allergy).
    • Pre-existing severe hypokalemia or hyponatremia.
    • Marked renal or hepatic dysfunction.

      ⭐ Can precipitate hepatic encephalopathy in patients with liver cirrhosis due to increased NH3 reabsorption in PCT and decreased NH4+ excretion.

    • Established hyperchloremic acidosis.
    • Adrenal insufficiency (e.g., Addison's disease).
    • Severe Chronic Obstructive Pulmonary Disease (COPD) - may worsen respiratory acidosis.

High‑Yield Points - ⚡ Biggest Takeaways

  • Acetazolamide is the prototype Carbonic Anhydrase Inhibitor.
  • Primarily acts at the Proximal Convoluted Tubule (PCT).
  • Mechanism: Inhibits carbonic anhydrase, ↓ HCO₃⁻ reabsorption & Na⁺ reabsorption.
  • Leads to mild diuresis and metabolic acidosis (hyperchloremic, non-anion gap).
  • Key uses: Glaucoma, acute mountain sickness, epilepsy, metabolic alkalosis.
  • Common side effects: Paresthesias, hypokalemia, renal stones (calcium phosphate), sulfa allergy.
  • Contraindicated in hepatic cirrhosis (↑ risk of encephalopathy) and known sulfa allergy.

Practice Questions: Carbonic Anhydrase Inhibitors

Test your understanding with these related questions

What is the mechanism of action of acetazolamide in the treatment of glaucoma?

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Flashcards: Carbonic Anhydrase Inhibitors

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_____ and HCTZ are diuretics that may cause pancreatitis as an adverse effect.

TAP TO REVEAL ANSWER

_____ and HCTZ are diuretics that may cause pancreatitis as an adverse effect.

Furosemide

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