1. Carbonic Anhydrase Inhibitor

2. Preparation & Chemistry Acetazolamide Methazolamide sulfonamide derivatives Dichlorphenamide

3. Mechanism of action Reversibly inhibit CA enzyme in proximal convoluted tubule cause - reduction in hydrogen ion for Na+--H+ exchange - Suppress CO2 reabsorption from glomerular filtrate - Na+-HCO3- excretion is increased # lead to production of alkaline urine

4. To maintain ionic balance, Cl- is retained by kidney cause Hyperchloremic acidosis induce Refractory state and decrease diuresis

5. High concentration of CA occur in ciliary process of eye CA enzyme involve in aqueous humor formation CA inhibitors reduce intraocular pressure in glaucoma by decreasing production of aqueous humor.

6. Therapeutic uses Reduce the rate of aqueous humors formation in treatment of glaucoma Use as adjuncts in treatment of metabolic alkalosis

7. Pharmacokinetics Acetazolamide and dichlorphenamide are absorb orally distributed to tissue with high CA concentration (renal cortex, eye and RBC) Excreted by kidney by active secretion and passive reabsorption. Onset of diuretic action is 30 mins with a duration of 6-12 hours in small animal.

8. Horse - IV # Distribution t1/2:60 mins # Elimination t1/2:~ 7.5 hours - Orally # reach peak plasma level ~ 2 hours # bioavailability of acetazolamide:~25%

9. Administration For glaucoma-acetazolamide, metazolamide, ethazolamide or dichlorphenamide given orally 2-3 times daily. Acute cases: 1 IV dose of acetazolamide followed by an oral dosage.

10. Adverse effect Toxicity is rare. GI disturbance- vomitting after oral administration. Contraindicated in presence of liver disease because they may precipitate hepatic coma by diverting ammonia produce in kidney from the urine to the systemic circulation as a result of urine alkalinization.