Carbonic Anhydrase Inhibitor

Preparation & Chemistry

• Acetazolamide

• Methazolamide sulfonamide derivatives

• Dichlorphenamide

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

To maintain ionic balance, Cl- is retained by kidney cause

Hyperchloremic acidosis induce

Refractory state and decrease diuresis

• 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.

Therapeutic uses

• Reduce the rate of aqueous humors formation in treatment of glaucoma

• Use as adjuncts in treatment of metabolic alkalosis

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.

• Horse- IV# Distribution t1/2:60 mins

# Elimination t1/2:~ 7.5 hours

- Orally# reach peak plasma level ~ 2 hours# bioavailability of acetazolamide:~25%

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.

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.