Carbonic anhydrase inhibitors glaucoma with

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. 

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

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. 

Q10 Beta-adrenoceptor antagonists are contraindicated in patients with asthma or respiratory obstructive diseases, bradycardia, heart block or heart failure. Adrenergic agonists are contraindicated in patients with closed-angle glaucoma and should be used cautiously in patients with hypertension or heart disease. Parasympathomimetics cause poor night vision and dimming of vision, because of development of miosis, headache and brow ache. Carbonic anhydrase inhibitors have a weak diuretic action and can induce depression, drowsiness, paraesthesia, electrolyte disturbance such as hypokalaemia, acidosis and lack of appetite. 

Patients with bullous keratopathy should have their lOP measured (even though corneal edema results in underestimated lOP) because angle-closure glaucoma can cause similar corneal edema. In addition, patients with Fuchs dystrophy have an increased risk of developing open-angle glaucoma in addition to the bullous keratopathy. Topical carbonic anhydrase inhibitors should be avoided in these patients because of the potential of worsening the corneal decompensation. 

The carbonic anhydrase inhibitors, of which acetazol-amide (rINN), a non-competitive inhibitor, is the prototype, are not suitable for normal diuretic use, because tolerance soon develops. However, they are well suited to brief intermittent use, particularly in the relief of glaucoma and in the prevention of acute mountain sickness. Acetazolamide and methazolamide (rINN) should be used with caution in the long-term control of glaucoma because of its serious systemic adverse effects. However, brinzolamide (rINN) and dorzolamide (rINN) are available for long-term topical administration. 

Nesher R, Ticho U. Switching from systemic to the topical carbonic anhydrase inhibitor dorzolamide effect on the quality of life of glaucoma patients with drug-related side effects. Isr Med Assoc J 2003 5(4) 260-3. 

Figure 28-28 Dorzolamide (Trusopt), 1. also a constituent of Cosopt, was the first drug designed with structure-based CAOO methods to become commercially available. MK-927. 21, IS a close structural analogue and was the first carbonic anhydrase inhibitor to lower intraocular pressure In glaucoma patients...

Carbonic anhydrase inhibitors are used for long-term treatment of open-angle glaucoma, interfering with the production of carbonic acid, which results in decreased IOP. 

Figure 15. Chemical structures of the carbonic anhydrase inhibitors 15-21. The small aromatic sulfonamides 15 and 16 bind with nanomolar affinity to carbonic anhydrase. Methazolamide 18 was used for a long time to treat glaucoma. 19 was the first topically active inhibitor. Structure-based drug design at Merck first led to 20 and then to the marketed drug, dorzolamide 21.

An even more extreme situation is found with carbonic anhydrase inhibitors such as ac-etazolamide, ethoxyzolamide, and methazol-amide, which are useful for the treatment cf glaucoma. Because of their limited aqueous solubility or unfavorable lipophilicity,they are not active when given topically to the eye and must be given orally or parenterally. Systemic side effects severely limit this mode of therapy and, consequently, numerous investigations are presently under way to find a new carbonic anhydrase inhibitor that readily penetrates the cornea or to prepare a prodrug with adequate water solubility and lipophilicity combined with the ability to be reconverted to the parent sulfonamide after corneal passage (255-257). 

Brinzolamide is a carbonic anhydrase inhibitor that causes an inhibition of carbonic anhydrase in the cihary processes of the eye deaeases aqueous. It is indicated in the treatment of elevated lOP inpatients with ocular hypertension or open-angle glaucoma. The development of topical carbonic anhydrase inhibitor took many years but was an important event because of the poor side-effect profile of oral carbonic anhydrase inhibitors (CAIs). Dorzolamide (Trusopt) and brinzola-mide both work by inhibiting carbonic anhydrase (isoenzyme n), which is found in the ciliary body epithehum. This reduces the formation of bicarbonate ions, which reduces fluid transport and thus lOP. hi fact, the P-receptor antagonist timolol has been combined with the carbonic anhydrase inhibitor dorzolamide in a single medication (Cosopt). 

Dorzolamide is a carbonic anhydrase inhibitor that inhibits carbonic anhydrase enzyme, reducing the rate of aqueous humor formation and thus lowering intraocular pressure (lOP). It is indicated in the treatment of elevated lOP in patients with ocular hypertension or open-angle glaucoma. 

This topically active carbonic anhydrase inhibitor is a powerful controller of the elevated intraocular pressure associated with glaucoma, and has been prepared by Merck in > 32% yield in a multistep synthesis starting from (R)-3-hydroxybutyrate [49]. Although the key ketone reduction step has been recently improved by researchers at Zeneca by replacing a chemical process with a biological one [50], the Merck synthesis well illustrates the potentialities of the approach to enantiomerically pure drugs based on the use of chiral non-racemic substrates. 

With prolonged use of the carbonic anhydrase Inhibitor diuretics, the urine becomes more alkaline, and the blood becomes more acidic. When acidosis occurs, the carbonic anhydrase Inhibitors lose their effectiveness as diuretics. They remain Ineffective until normal acid-base balance In the body has been regained. For this reason, this class of compounds Is limited In Its diuretic use. Today, they are most commonly used In the treatment of glaucoma. In which they reduce the rate of aqueous humor formation and, subsequently, reduce the Intraocular pressure. These compounds also have found some limited use In the treatment of absence seizures, to alkallnize the urine, to treat familial periodic paralysis, to reduce metabolic alkalosis, and prophylactically, to reduce acute mountain sickness. 

Acetazolamide was the first of the carbonic anhydrase Inhibitors to be Introduced as an orally effective diuretic, with a diuretic effect that lasts approximately 8 to 12 hours (see Table 27.2 for Its pharmacokinetic properties). As mentioned earlier. Its diuretic action Is limited because of the systemic acidosis it produces. Acetazolamide reduces the rate of aqueous humor formation and is used primarily for reducing intraocular pressure in the treatment of glaucoma. The dose is 250 mg to 1 g per day. 

Carbonic anhydrase inhibitors are used to decrease intraocular pressure in patients with open-angle (chronic) glaucoma and are not used in narrow-angle or acute glaucoma. Other uses include inducing diuresis, management of epilepsy, and treatment of high-altitude or acute mountain sickness. 

Carbonic anhydrase inhibitors are used as a long-term treatment for open-angle glaucoma by decreasing intraocular pressure by interfering with the production of aqueous humor. Patients who take carbonic anhydrase inhibitors can experience lethargy, anorexia, drowsiness, paresthesia, depression, polyuria, nausea, vomiting, hypokalemia, and renal calculi. It is because of these adverse side... 

The client diagnosed with glaucoma is prescribed oral acetazolamide (Diamox), a carbonic anhydrase inhibitor. Which information should the client discuss with the client ... 

Dorzolamide was launched in 1995 as a treatment for glaucoma. It inhibits human carbonic anhydrase II (HCA II) and lowers ocular pressure. It is based on a thienothiopyran-2-sulfonamide scaffold, which was first reported in 1987 as a class of carbonic anhydrase inhibitor with good aqueous solubility... 

A -Alkyl and sulfonamide derivatives of the 1,2,3-benzothiazine-l,1-dioxides 40, whose synthesis is shown in Schemes 1 and 2, are inhibitors of carbonic anhydrase <1995USP5464831, 1996USP5510347>. These compounds are used as a treatment for chronic primary angle glaucoma that is associated with a sustained increase in the intraocular pressure of the diseased eye. Topical administration of carbonic anhydrase inhibitors can be used to control intraocular pressure with a reduced risk of side effects such as nausea, dyspepsia, fatigue, and metabolic acidosis. 

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