Toxicity of Acetazolamide

Acetazolamide is a carbonic anhydrase inhibitor. Under normal physiological conditions, the enzyme carbonic anhydrase is responsible for reabsorption of Na+ and excretion of H+ in the PCT of the nephron. 

Metabolic mechanism

Inhibition of carbonic anhydrase decreases H⁺ excretion, and therefore Na⁺ and HCO^{3 –} ions stay in the renal tubule. This results in the production of alkaline urine with high Na⁺ and HCO^{3 –} content. Delivery to the collecting tubules of this Na⁺ HCO^{3 –}load will enhance K⁺ secretion, causing a resultant kaliuresis, and can worsen hypokalaemia. 

The increased Na⁺ excretion leads to a modest diuresis. Cl^– is retained instead of HCO^{3 –} to maintain an ionic balance. All these changes result in a hyperchloraemic metabolic acidosis. A cetazolamide is well absorbed, not metabolised, and is excreted almost unchanged by the kidney within 24h. 

Medical uses

It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, epilepsy and in reducing intraocular pressure after surgery.It has also been used in the treatment of altitude sickness,Ménière's disease, increased intracranial pressure and neuromuscular disorders.

In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.Though various websites on the internet report that acetazolamide can be used to treat dural ectasia in individuals with Marfan Syndrome, the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication.

Toxicity

Toxicity is very rare. The adult oral and intravenous dose is 250–1000 mg day^–1 in divided doses. Carbonic anhydrase inhibitors are seldom used as primary diuretics because of their weak diuretic effect. They are mainly used in the setting of prevention and management of acute mountain sickness or treatment of raised intraocular pressure. They are occasionally used in the setting of intensive care to promote urinary HCO^{3 –} loss in patients with metabolic alkalosis and raised HCO^3–.

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