Carbonic anhydrase inhibitors effects

Food containing salicylate (curry powder, paprika, licorice, prunes, raisins, and tea) may increase the risk of adverse reactions. Coadministration of the salicylates with activated charcoal decreases the absorption of the salicylates. Antacids may decrease the effects of the salicylates. Coadministration with the carbonic anhydrase inhibitors increases the risk of salicylism. Aspirin may increase the risk of bleeding during... 

Carbonic anhydrase is an enzyme that produces free hydrogen ions, which are then exchanged for sodium ions in the kidney tubules. Carbonic anhydrase inhibitors inhibit the action of the enzyme carbonic anhydrase This effect results in the excretion of sodium, potassium, bicarbonate, and water. Carbonic anhydrase inhibitors also decrease the production of aqueous humor in the eye, which in turn decreases intraocular pressure (IOP) (ie, the pressure within the eye). 

Local side effects include burning, stinging, itching, foreign body sensation, dry eyes, and conjunctivitis. Brinzolamide may have a lower incidence of these side effects since the drug is in a neutral pH solution. Dorzolamide has been reported to cause irreversible corneal decompensation. Taste abnormalities have been reported with each agent. Both topical carbonic anhydrase inhibitors are sulfonamides and are contraindicated in patients with history of sulfonamide hypersensitivity.10,13... 

The systemic carbonic anhydrase inhibitors are associated with significant adverse effects which include paresthesias of the hands and feet, nausea, vomiting, and weight loss. Patients... 

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. 

Carbonic anhydrase inhibitor lOP Lowering Effects Relative inhibitor potency... 

Paresthesia Paresthesia, an effect associated with the use of other carbonic anhydrase inhibitors, appears to be a common effect of topiramate. 

Concomitant oral carbonic anhydrase inhibitors There is a potential for an additive effect of the known systemic effects of carbonic anhydrase (CA) inhibition in patients receiving an oral and ophthalmic CA inhibitor. The concomitant administration of ocular and oral CA inhibitors is not recommended. 

Dorzolamide (Trusopt) [Carbonic Anhydrase Inhibitor, Sul-fonamide/Glaucoma A9ent] Uses Glaucoma Action Carbonic anhydrase inhibitor Dose 1 gtt in eye(s) tid Caution [C, ] Contra Component sensitivity Disp Soln SE Irritation, bitter taste, punctate k atitis, ocular all gic Rxn EMS t Effects W/ oral carbonic anhydrase inhibitors, salicylates EMS Drug is absorbed systemicaUy OD May cause electrolyte disturbances (K) and acidosis monitor ECG... 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Inhibition of proximal tubule brush border carbonic anhydrase decreases bicarbonate reabsorption, and this accounts for their diuretic effect. In addition, carbonic anhydrase inhibitors affect both distal tubule and collecting duct H+ secretion by inhibiting intracellular carbonic anhydrase. 

X. de Leval, M. Hies, A. Casini, J.M. Dogne, A. Scozzafava, E. Masini, F. Mincione, M. Starnotti, C.T. Supuran, Carbonic anhydrase inhibitors Synthesis and topical intraocular pressure lowering effects of fluorine-containing inhibitors devoid of enhanced reactivity, J. Med. Chem. 47 (2004) 2796-2804. 

Adverse effects associated with brinzolamide are similar to those of other carbonic anhydrase inhibitors. In clinical experience with topical ocular administration of brinzolamide, events including transient, momentary blurred vision, bitter, and sour or unusual taste were reported in approximately 5 % - 10% of patients. Ocular discomfort, discharge or other ocular signs, and headache were reported at an incidence of 1 -5% [15]. 

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. 

Mechanism of Action A carbonic anhydrase inhibitor that reduces formation of hydrogen and bicarbonate ions from carbon dioxide and water by inhibiting, in proximal renal tubule, the enzyme carbonic anhydrase, thereby promoting renal excretion of sodium, potassium, bicarbonate, and water. Ocular Reduces rate of aqueous humor formation, lowers intraocular pressure. Therapeutic Effect Produces anticonvulsant activity. 

Thieno[2,3- ]thiopyran derivatives, 164, show effective activity as carbonic anhydrase inhibitors, especially as intraocular pressure-lowering agents <1999JME2641>. 

When carbonic anhydrase inhibitors block the enzyme in the kidney, HjCOj formation— and consequently the availability of H3O+ (i.e., protons)—decreases. Since the Na+ ions in the filtrate cannot be exchanged, sodium is excreted, together with large amounts of water, as a result of ion hydration and osmotic effects. The result is diuresis, accompanied by a dramatic increase in urine volume. There is also failure to remove HCOj" ions because there is no H3O+ to form HjCOj, which would decompose to COj -1- HjO. Therefore, the normally slightly acidic urine becomes alkaline. The strong carbonic anhydrase inhibitors also increase K+ excretion, an undesirable effect. 

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. 

Other drugs, such as verapamil, caffeine, theophylline, osmotic diuretics, carbonic anhydrase inhibitors, or aminophylline, can increase lithium excretion, possibly dropping plasma levels below the therapeutic threshold ( 329). Further, if doses are increased to compensate for this effect, care must be taken to readjust the lithium downward when these concomitant agents are reduced or discontinued. 

Alprazolam may also relieve tremor at doses of 0.75 to 3 mg/day (357). Because chronic use can lead to habituation or dependence, alprazolam is best used episodically for patients who require only intermittent tremor reduction to prevent social embarrassment or occupational interference. Methazolamide, a carbonic anhydrase inhibitor, has been reported to reduce hand tremor (at doses of 50 to 300 mg/day) in several open studies ( 358, 359). A controlled trial, however, could not confirm the efficacy of this agent in the treatment of tremor but did report that side effects such as paresthesias, sedation, headache, and gastrointestinal symptoms were common (77, 356). 

The reduction of aqueous humor formation by carbonic anhydrase inhibitors decreases the intraocular pressure. This effect is valuable in the management of glaucoma, making it the most common indication for use of carbonic anhydrase inhibitors. Topically active carbonic anhydrase inhibitors (dorzolamide, brinzolamide) are available and reduce intraocular pressure without producing detectable plasma levels. Thus, diuretic and systemic metabolic effects are eliminated for the topical agents. 

Acidosis predictably results from chronic reduction of body HC03 stores by carbonic anhydrase inhibitors (Table 15-2) and limits the diuretic efficacy of these drugs to 2 or 3 days. Unlike the diuretic effect, acidosis persists as long as the drug is continued. 

Another carbonic anhydrase inhibitor, sulthiame, was not found to be effective as an anticonvulsant in clinical trials in the USA. It is marketed in some other countries. 

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