Mountain sickness, treatment

Aceta2olamide, the best example of this class of diuretics (69,70), is rarely used as a diuretic since the introduction of the thia2ides. Its main use is for the treatment of glaucoma and some minor uses, eg, for the a1ka1ini2ation of the urine to accelerate the renal excretion of some weak acidic dmgs, and for the prevention of acute high altitude mountain sickness. 

Inhibitors to the enzyme carbonic anhydrase. This enzyme is widely distributed in the body and has a fundamental role in the control of acid-base balance. In the 1920s it was noticed that the SULPHONAMIDE sulfanilamide had a weak diuretic action. Acetazolamide is a subsequent thiadiazole-sulphonamide derivative with potent carbonic anhydrase inhibitor activity. Clinically, it is used for antiglaucoma TREATMENT, is a weak diuretic and can be used to treat mountain sickness. Dichlorphenamide and dorzolamide are sulphonamide derivatives also used for antiglaucoma treatment. Methazolamide is used as a diuretic. Now that seven or more isoenzymes of carbonic anhydrase have been cloned. Isolated and mapped, some new initiatives are aimed at developing agents with more selective actions. 

Consequently, diuretics have a variety of uses. Thiazide diuretics may be used either alone or in combination with other pharmacotherapy for the treatment of hypertension. Loop diuretics can provide immediate diuresis and are used for heart failure and in lieu of thiazides in patients with compromised renal function. In addition to more traditional uses, certain potassium-sparing diuretics provide added benefit to other pharmacotherapy in patients with primary hyperaldosteronism, heart failure, or post-acute myocardial infarction. Carbonic anhydrase inhibitors have limited use for diuresis however, they may be used to reduce intraocular pressure and treat acute mountain sickness. 

With prolonged use of the carbonic anhydrase Inhibitor diuretics, the urine becomes more alkaline, and the blood becomes more acidic. When acidosis occurs, the carbonic anhydrase Inhibitors lose their effectiveness as diuretics. They remain Ineffective until normal acid-base balance In the body has been regained. For this reason, this class of compounds Is limited In Its diuretic use. Today, they are most commonly used In the treatment of glaucoma. In which they reduce the rate of aqueous humor formation and, subsequently, reduce the Intraocular pressure. These compounds also have found some limited use In the treatment of absence seizures, to alkallnize the urine, to treat familial periodic paralysis, to reduce metabolic alkalosis, and prophylactically, to reduce acute mountain sickness. 

Carbonic anhydrase inhibitors are used to decrease intraocular pressure in patients with open-angle (chronic) glaucoma and are not used in narrow-angle or acute glaucoma. Other uses include inducing diuresis, management of epilepsy, and treatment of high-altitude or acute mountain sickness. 

C. Clinical Uses The major application of carbonic anhydrase inhibitors is in the treatment of glaucoma. Acetazolamide must be administered orally, but topical analogs are now available (dorzolamide, brinzolamide) for use in the eye. Carbonic anhydrase inhibitors are also used to prevent acute mountain (high-altitude) sickness. These agents are used for their diuretic effect only if edema is accompanied by significant metabolic alkalosis. 

---