Carbonic anhydrase inhibitors toxicity

Since the 1950s, diuretic therapy has changed dramatically. Earlier, the major diuretics were acidforming salts, xanthines, organomercurial compounds, and carbonic anhydrase inhibitors. Either because of toxicity or lack of efficacy, these agents are rarely if ever used. 

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. 

Carbonic anhydrase inhibitors [NE] Increased acetazolamide serum concentrations increase salicylate toxicity due to decreased blood pH. 

Salicylates Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. Salicylates may displace drugs from plasma protein binding sites. Carbonic anhydrase inhibitors [NE] Increased acetazolamide serum concentrations increased salicylate toxicity due to decreased blood pH. 

DISOPYRAMIDE DIURETICS-CARBONIC ANHYDRASE INHIBITORS, LOOP DIURETICS, THIAZIDES Risk oft myocardial depression Cardiac toxicity directly related to hypokalaemia Monitor potassium levels closely... 

ASPIRIN CARBONIC ANHYDRASE INHIBITORS t risk of salicylate toxicity with high-dose aspirin Uncertain at present Use low-dose aspirin... 

CARBONIC ANHYDRASE INHIBITORS ANTIDEMENTIA DRUGS-MEMANTINE Possibly t memantine levels 1 renal excretion Watch for early features of memantine toxicity... 

CARBONIC ANHYDRASE INHIBITORS CARDIAC GLYCOSIDES Risk of digoxin toxicity t by acetazolamide due to hypokalaemia Uncertain Monitor potassium levels closely. Watch for digoxin toxicity and check levels... 

SAFETY PROFILE Poison by subcutaneous and intravenous routes. Moderately toxic by intraperitoneal route. Human systemic effects by ingestion dyspnea. An experimental teratogen by many routes. Other experimental reproductive effects. When heated to decomposition it emits ver toxic fumes of NOx and SOx. A carbonic anhydrase inhibitor and diuretic used to treat glaucoma. 

Echothiophate iodide has found therapeutic appiication for the treatment of giaucoma and strabismus. Echothiophate is applied topically as a solution and is the only irreversible AChEI for the treatment of glaucoma. The decrease in intraocular pressure observed can last up to 4 weeks. Phosphoester AChEls exhibit cataractogenic properties thus, their use should be reserved for patients who are refractory to other forms of treatment (i.e., short-acting miotics, (3-blockers, epinephrine, and possibly, carbonic anhydrase inhibitors). Because of its toxicity, echothiophate is not used for its systemic action. Selectivity of echothiophate for the AChE catalytic site was enhanced by incorporation in the molecule of a quaternary ammonium salt functional group two carbons removed from the phosphoryl group. 

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. ... 

Anderson CJ, Kaufman PL, Sturm RJ. Toxicity of combined therapy with carbonic anhydrase inhibitors and aspirin. Am J Ophthalmol (1978) 86, 516-19. 

Hurwitz GA Wingfield W, Cowart TD, Jollow DJ. Toxic interaction between salicylates and a carbonic anhydrase inhibitor the role of cerebral edema. Vet Hum Toxicol (1980) 22 (Siq)pl),... 

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