Carbonic anhydrase inhibitors acetazolamide

Carbonic anhydrase inhibitor Acetazolamide Osmotic agent Mannitol Loop Diuretics ... 

Carbonic anhydrase inhibitors Acetazolamide Ethoxzolamide Dichlorphenamide... 

A severe and even life-threatening toxic reaction can occur in patients taking high-dose salicylates if they are given carbonic anhydrase inhibitors (acetazolamide, diclofenamide). 

Not fully established. One idea is that these carbonic anhydrase inhibitors (acetazolamide, diclofenamide) affect the plasma pH, so that more of the salicylate exists in the un-ionised (lipid-soluble) form, which can enter the CNS and other tissues more easily, leading to salicylate toxicity. However, carbonic anhydrase inhibitors also make the urine more alkaline, which increases the loss of salicylate (see also Aspirin or other Salicylates + Antacids , p.l35). Animal studies confirm that carbonic anhydrase inhibitors increase the lethal toxicity of aspirin. An alternative suggestion is that because salicylate inhibits the plasma protein binding of acetazolamide and its excretion by the kidney, acetazolamide toxicity, which mimics salicylate toxicity, may occur. ... 

There are a relatively large number of compounds that might be grouped together under the heading of sulphonamide diuretics. Within the group of compounds containing this functionality, we have a variety of different classes of diuretics based on their mechanism of action. These compounds are considered active as carbonic anhydrase inhibitors (acetazolamide), inhibitors of the reabsorption of Na+ Cl (thiazide and thiazide-like diuretics [benzthia-zide, hydrochlorothiazide]) and inhibitors of the Na K Cl symporter (fiirosemide). 

Not all drugs contain functional groups that lend themselves readily to prodrug derivatization. A case in point is the carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, and methazolamide. Although the amino functional group of their sulfonamide moiety can be methylated, the resulting analogs... 

Carbonic anhydrase inhibitors such as acetazolamide act in the proximal tubule. These drugs prevent the formation of H+ ions, which are transported out of the tubular epithelial cell in exchange for Na+ ions. These agents have limited clinical usefulness because they result in development of metabolic acidosis. 

The answer is c. (Hardman, pp 6917 693 J Acetazolamide is a carbonic anhydrase inhibitor with its primary site of action at the proximal tubule of the nephron. Acetazolamide promotes a urinary excretion of Na, K, and bicarbonate There is a decrease in loss of Cl ions The increased excretion of bicarbonate makes the urine alkaline and may produce metabolic acidosis as a consequence of the loss of bicarbonate from the blood. None of the other diuretic drugs promote a reduction in the excretion of the Cl ion... 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Acetazolamide is a carbonic anhydrase inhibitor, used primarily in glaucoma to reduce aqueous humour production. Acetazolamide may cause blood disorders including agranulocytosis (deficiency of neutrophils) as a side-effect. 

Acetazolamide is a carbonic anhydrase inhibitor, which reduces intraocular pressure by reducing aqueous humour production. It is used in the treatment of glaucoma. Acetazolamide is administered systemically. Recently newer carbonic anhydrase inhibitors have been developed, which are available as topical agents (for example, dorzolamide). 

Acetazolamide is a carbonic anhydrase inhibitor that is administered orally for the treatment of glaucoma. Topical carbonic anhydrase inhibitors include dorzolamide and brinzolamide. Carbonic anhydrase inhibitors reduce the production of aqueous humour, thereby reducing intraocular pressure. They can be used alone or in addition to beta-blocker therapy in glaucoma patients. 

Acetazolamide is an aromatic sulfonamide used as a carbonic anhydrase inhibitor. It facilitates production of alkahne urine with an elevated biocarbonate, sodium, and potassium ion concentrations. By inhibiting carbonic anhydrase, the drug suppresses reabsorption of sodium ions in exchange for hydrogen ions, increases reflux of bicarbonate and sodium ions and reduces reflux of chloride ions. During this process, chloride ions are kept in the kidneys to cover of insufficiency of bicarbonate ions, and for keeping an ion balance. Electrolytic contents of fluid secreted by the kidneys in patients taking carbonic anhydrase inhibitors are characterized by elevated levels of sodium, potassium, and bicarbonate ions and a moderate increase in water level. Urine becomes basic, and the concentration of bicarbonate in the plasma is reduced. 

Orally administered carbonic anhydrase inhibitors lower the intraocular pressure of glaucoma patients, however they induce a number of intolerable side effects associated with extraocular inhibition of the enzyme [5,6]. Thus, much research has been directed towards the search for a topically effective agent. Several compounds have been synthesized since the 1980 s in Merck Sharp Dohme Research Laboratories, and have been found to be topically active in man [7]. Unfortunately, many of these compounds were not very soluble. Attempts to obtain an active carbonic anhydrase inhibitor with good solubility resulted in the synthesis of Dorzolamide hydrochloride [8,9], which was first made available for pharmacological evaluation in 1987. Like other carbonic anhydrase inhibitors sulfonamides (such as acetazolamide, ethoxzolaniide, and methazolamide) dorzolamide is an inhibitor of human carbonic anhydrase isoenzymes I, II, and IV. In contrast to the other sulfonamides, dorzolamide is a potent inhibitor of isoenzymes II and IV, and a weak inhibitor of isoenzyme I [ 10]. Isoenzyme II is thought to play a major role in aqueous humor secretion. 

The development of sulfonamide carbonic anhydrase inhibitors was based on the observation that antibacterial sulfanilamides produce alkaline urine. This discovery led to the development of acetazolamide (8.29), a thiadiazole derivative. It is not an ideal drug because it promotes K+ excretion and causes a very high urine pH. Since chloride ions are not excreted simultaneously, systemic acidosis also results. Much more useful are the chlorothiazide (8.30) derivatives, which are widely used as oral diuretic drugs. These compounds differ from one another mainly in the nature of the substituent on C3 ... 

Acetazolamide (a carbonic anhydrase inhibitor) used as diuretic by increasing bicarbonate excretion and thus acidosis occur as side effect which is related to its pharmacological action. 

Almost all diuretics exert their action at the luminal surface of the renal tubule cells. Their mechanism of action includes interaction with specific membrane transport proteins like thiazides, furosemide etc., osmotic effects which prevent the water permeable segments of the nephron from absorbing water like mannitol, and specific interaction with enzyme like carbonic anhydrase inhibitors i.e. acetazolamide, and hormone receptors in renal epithelial cells like spironolactone. 

Bicarbonate reabsorption by the proximal tubule is thus dependent on carbonic anhydrase. This enzyme can be inhibited by acetazolamide and other carbonic anhydrase inhibitors. 

Carbonic anhydrase inhibitors were the forerunners of modern diuretics. They were discovered when it was found that bacteriostatic sulfonamides caused an alkaline diuresis and hyperchloremic metabolic acidosis. With the development of newer agents, carbonic anhydrase inhibitors are now rarely used as diuretics, but they still have several specific applications that are discussed below. The prototypical carbonic anhydrase inhibitor is acetazolamide. 

At present, the major clinical applications of acetazolamide involve carbonic anhydrase-dependent HC03 and fluid transport at sites other than the kidney. The ciliary body of the eye secretes HC03 from the blood into the aqueous humor. Likewise, formation of cerebrospinal fluid by the choroid plexus involves HC03 secretion. Although these processes remove HC03 from the blood (the direction opposite of that in the proximal tubule), they are similarly inhibited by carbonic anhydrase inhibitors. 

Drowsiness and paresthesias are common following large doses of acetazolamide. Carbonic anhydrase inhibitors may accumulate in patients with renal failure, leading to nervous system toxicity. Hypersensitivity reactions (fever, rashes, bone marrow suppression, and interstitial nephritis) may also occur. 

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