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.
Clinical Uses - Pressure Relief
Acetazolamide is the primary CAI used for conditions where reducing fluid pressure is beneficial.
| Use | Rationale 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.
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