Carbonic anhydrase inhibitors

Proximol convulated tube

Bicarbonate reabsorption is initiated by the action of Na⁺/H⁺ ion exchanger which allows Na⁺ to enter into the cell and hydrogen into lumen part of nephron.

In the lumen bicarbonate is Combined with H⁺ and form carbonic acid which is rapidly dehydrated to H₂O and CO₂ with the help of an enzyme and Carbonic anhydrase. CO₂ enters Into the epithelial cell by Simple diffusion and get H₂O  to form Carbonic acid by intracellular Carbonic anhydrase. Now, this intracellular Carbonic acid dissociates to forms hydrogen ion and bicarbonate. This hydrogen ion (H⁺) gets back to the lumen through Na⁺/H⁺ ion exchanger and bicarbonate Ion (HCO₃) is transported to the blood. When Carbonic anhydrase inhibitors are introduced they inhibit Carbonic anhydrase enzyme which reduces the reabsorption of bicarbonate.

Now due to this excessive fluid is excrted out in urine and helps to treat disease like Hypertention,Edema etc.

Exm: Acetazolamide

Pharmacokinetics

Acetazolamide is well absorbed orally and excreted unchanged in urine. Action of a single dose lasts 8–12 hours.

Uses:

     I.          Used as mild uritic agents.

  II.          used in the treatment of gloucoma and drug induced edema.

III.          also used as anticonvulsant for treatment of epilepsy.

IV.          Also used in the treatment of menier’s disease.

 

Adverse effects are frequent.

 I.   Acidosis, hypokalaemia, drowsiness, paresthesias, fatigue, abdominal discomfort.

II.    Hypersensitivity reactions—fever, rashes.

     III.   Bone marrow depression is rare but serious.

    IV.    It is contraindicated in liver disease: may precipitate hepatic coma by interfering with urinary elimination of NH3 (due to alkaline urine).

    V.    Acidosis is more likely to occur in patients of COPD.