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Diuretics- Acetazolamide and Carbonic Anhydrase Inhibitors Pharmacology

Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), and heart failure. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out.It is taken by mouth or injection into a vein.
The mechanism of diuresis involves the proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul respiration), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.

In the eye this results in a reduction in aqueous humour.
In short, under normal conditions, the net effect of carbonic anhydrase in the urinary lumen and cells of the proximal convoluted tubule is to acidify the urine and transport bicarbonate (HCO3−) into the body. Another effect is excretion of Cl− as it is needed to maintain electroneutrality in the lumen, as well as the reabsorption of Na+ into the body.

Thus, by disrupting this process with acetazolamide, urinary Na+ and bicarbonate (HCO3−) are increased, and urinary H+ and Cl−are decreased. Inversely, serum Na+ and bicarbonate (HCO3−) are decreased, and serum H+ and Cl− are increased. H2O generally follows sodium, and so this is how the clinical diuretic effect is achieved, which reduces blood volume and thus preload on the heart to improve contractility and reduce blood pressure, or achieve other desired clinical effects of reduced blood volume such as reducing edema or intracranial pressure


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