Glaucoma carbon anhydrase inhibitors

The major indication for carbonic anhydrase inhibitors is open-angle glaucoma. Carbonic anhydrase inhibitors also may be employed for secondary glaucoma and preop-eratively in acute angle-closure glaucoma to lower intraocular pressure before surgery. Acetazolamide also is used for the treatment of epilepsy. The rapid development of tolerance, however, may limit the usefulness of carbonic anhydrase inhibitors for epilepsy. 

Therapeutic Function Carbonic anhydrase inhibitor, diuretic, treatment of glaucoma Chemical Name N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl] acetamide Common Name —... 

Therapeutic Function Carbonic anhydrase inhibitor glaucoma treatment Chemical Name 48-Olchloro-m-benzenedisulfonamide Common Name DIclofenamid... 

The carbonic anhydrase inhibitors are contraindicated in patients with known hypersensitivity to the dru , electrolyte imbalances, severe kidney or liver dysfunction, or anuria, and for long-term use in chronic non-congestive angle-closure glaucoma (may mask worsening glaucoma). 

Carbonic anhydrase inhibitors During treatment for glaucoma, contact the primary health care provider immediately if eye pain is not relieved or if it increases. When a patient with epilepsy is being treated for seizures, a family member of the patient should keep a record of all seizures witnessed and bring this to the primary health care provider at die time of the next visit. Contact the primary healdi care provider immediately if die seizures increase in number. 

Viader MP, McKeever BM, Navia MA. Thienothiopyran-2-sulfonamides novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma. J Med Chem 1989 32 2510-13. 

CAI, carbonic anhydrase inhibitor. (From LesarTS, Fiscella RG, Edward D. Glaucoma. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. 

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. 

Glaucoma Management of open-angle (chronic simple) glaucoma may be used in combination with miotics, beta blockers, hyperosmotic agents, or carbonic anhydrase inhibitors. 

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... 

Dorzolamide Timolol (Cosopt) [Carbonic Anhydrase Inhibitor/Beta Adrener9ic Bloclcer] Uses Glaucoma Action Carbonic anhydrase inhibitor w/ i-adrenergic blocks Dose 1 gtt in eye(s) bid... 

A variety of thiophene-fused 1,2-thiazines have been prepared as carbonic anhydrase inhibitors for the treatment of glaucoma <2002JME888, 2000BMC957>. The drug brinzolamide (under the trade name Azopt ) 24 has recently been approved by the FDA. 

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. 

Table 15-3 Carbonic Anhydrase Inhibitors Used Orally in the Treatment of Glaucoma. ...

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. 

Carbonic anhydrase inhibitors such as dorzo-lamide (Trusopt) and dichlorphenamide (Daranide) are used to treat glaucoma patients and altitude sickness. Acetazolamide (Diamox), a carbonic anhydrase... 

Diuretics are most commonly available in pill form. In a hospital setting, they may be administered intravenously or injected. Carbonic anhydrase inhibitors may be administered in eye drop form [dorzolamide (Trusopt)] to glaucoma patients. 

Along the same lines, several groups of chemists at Merck successfully produced substantial quantities of various important pharmaceutical intermediates used in the preparation of drugs under development. Among these we can mention MK-0417 (7), a soluble carbonic anhydrase inhibitor useful to treat glaucoma,41 the LTD4 antagonist L-699392 (8),42 and the antiarrhythmic MK-499... 

---