Carbonic anhydrase inhibitors

A short review by Dr. SWETHA RANI AITHA
YOUTUBE LINK FOR AUDIO AND VIDEO-https://youtu.be/FwdDjKhXWVo

1. CARBONIC ANHYDRASE INHIBITORS(DIURETICS)

2. This enzyme is present in kidneys and also in various other tissues such as CNS, eyes, gastric mucosa, pancreas, RBCs. Carbonic Anhydrase enzyme INTRODUCTION There are many types of Carbonic Anhydrase Enzymes

3. Carbonic Anhydrase Inhibitors are a group of diuretics that act on S 2 segment of PCT by inhibiting the enzyme Carbonic Anhydrase Type IV CA enzyme is present on luminal / basolateral membrane and Type II in cytoplasm of epithelial cells of PCT . In the Kidneys there are two types of CA enzymes. They are type II and type IV CA enzymes. CARBONIC ANHYDRASE INHIBITORS

4. DRUGS: Acetazolamide Methazolamide Dichlorphenamide Dorzolamide Brinzolamide Zonisamide Ethoxzolamide Diuretic action is produced by Acetazolamide, when administered orally at a dose of 250 mg, BD.

5. GLOMERULUS Basolateral membrane Luminal membrane Na + Na + H + Na-H+ antiport HCO 3 - H 2 CO 3 CO 2 H 2 O H 2 O CO 2 H 2 CO 3 CAIV CAII Na + -HCO 3 - symport Na + HCO 3 - HCO 3 - NaHCO 3 BLOOD MECHANISM OF ACTION EXCRETION OF WATER, HCO 3 - ,Na + , K + PCT H + HCO 3 -

6. PHARMACOKINETICS Absorbed orally Highly distributed to tissues containing CA Not metabolized but actively secreted in PCT

7. Effect on Kidney- Inhibition of NaHCO 3 reabsorption in the PCT and inhibition of secretion of acids in the collecting duct. PHARMACODYNAMICS Hemodynamic effect- Decrease in RBF and GFR due to increased afferent arteriolar resistance triggered by tubulo-glomerular feedback. Effect on electrolyte excretion in urine- Increase in urinary excretion of Bicarbonates, Sodium, Potassium

8. CLINICAL USES Urinary Alkalinization ACE t A z O l AMIDES Heart Failure Glaucoma (eye) Oedema Acute mountain sickness (high altitude sickness) Idiopathic intracranial Hypertension Diuresis Metabolic alkalosis Petit mal epilepsy Uric acid and cystine stones Other conditions like Hyperphosphatemia, Familial periodic paralysis

9. ADVERSE EFFECTS H ypokalemia H yperchloremic metabolic acidosis H epatic encephalopathy S tone formation(calcium oxalate) S ulfonamide like effects F ever S edation P aresthesia H F S P

10. CONTRA INDICATIONS A S H S evere COPD. Hyperchloremic A cidosis H epatic cirrhosis DRUG INTERACTIONS M O Action of M ethenamine is blocked by CAIs CAIs reduce excretion of weak O rganic acids