Glaucoma aqueous humor

Glaucoma is an increase in the IOP that, if left untreated, can result in blindness. Normally the eye is filled with aqueous humor in an amount that is carefully regulated to maintain the shape of the eyeball. In glaucoma, aqueous humor is increased, which causes the IOP to rise and can, without treatment, damage the retina... 

Cholinesterase inhibitors are used to treat glaucoma and myasthenia gravis. In glaucoma, aqueous humor production exceeds outflow, resulting in increased intraocular pressure. In the presence of cholinesterase inhibitor eye drops, acetylcholine causes constriction of the sphincter muscle which surrounds the iris. The iris is drawn away from the canal of Schlemm, enhancing outflow of aqueous humor. 

Navajas EV, Martins JR, Melo LA, Jr, Saraiva VS, Dietrich CP, Nader HB, Belfort R, Jr. Concentration of hyaluronic acid in primary open-angle glaucoma aqueous humor. Exp Eye Res 2005 80 853-857. 

Brimonidine tartrate is an alph -adrenergic receptor agonist used to lower IOP in patients with open-angle glaucoma or ocular hypertension. This drug acts to reduce aqueous humor production and increase the outflow of aqueous humor. 

The (3-adrenergic blocking drugs decrease the rate of production of aqueous humor and thereby lower the IOP. These drugs are used to treat glaucoma... 

Except for dorzolamide and brinzolamide, carbonic anhy-drase inhibitors are administered systemically. Carbonic anhydrase is an enzyme found in many tissues of the body, including the eye Inhibition of carbonic anhydrase in Hie eye decreases aqueous humor secretion, resulting in a decrease of IOE These drugs are used in the treatment of elevated IOP seen in open-angle glaucoma... 

These drugs dilate the pupil (mydriasis), constrict superficial blood vessels of the sclera, and decrease the formation of aqueous humor. Depending on the specific drug and strength, these dru may be used before eye surgery in the treatment of glaucoma, for relief of minor eye irritation, and to dilate the pupil for examination of the eye... 

FIGURE 58-2. Anterior chamber of the eye and aqueous humor flow. (From Lesar TS, Fiscella RG, Edward D. Glaucoma. In DiPiro JT, Talbert RL, Yee GC, et a I, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1715, with permission.)... 

All of the following drugs are used topically in the treatment of chronic wide-angle glaucoma. Which of these agents reduces intraocular pressure by decreasing the formation of the aqueous humor ... 

Applied topically to the eye, p-blockers are used in the management of glaucoma they lower production of aqueous humor without affecting its drainage. 

Glaucoma Since drainage of aqueous humor is impeded during relaxation of the pupillary sphincter, intraocular pressure rises. 

Clinical use of reversible inhibitors is directed to eye, skeletal muscle, neuromuscular junctions, gastrointestinal tract, urinary tract, respiratory tract, and heart and used in treatment of glaucoma (an ocular disease caused by increased intraocular pressure due to inadequate drainage of aqueous humor at filtration angle), myasthenia gravis (an autoimmune disease... 

Beside the cardiac indications /3-blockers can be used in the therapy of glaucoma. Systemic but also the local application of these compounds can reduce intraocular pressure. The mechanism of this action is a reduced production of aqueous humor by the ciliary body. Although applied locally, jS-blockers might be absorbed in sufficient amounts to induce systemic side effects in susceptible individuals. 

The therapeutic effect of /8-blockers (topically applied) in open angle glaucoma is based upon the reduction of the production of aqueous humor, via a mechanism which is not known in detail. 

Epinephrine also has been used to lower intraocular pressure in open-angle glaucoma. Its use promotes an increase in the outflow of aqueous humor. Because epinephrine administration will decrease the filtration angle formed by the cornea and the iris, its use is contraindicated in angle-closure glaucoma under these conditions the outflow of aqueous humor via the filtration angle and into the venous system is hindered, and intraocular pressure may rise abruptly. 

Blockers can reduce intraocular pressure in glaucoma and ocular hypertension. The mechanism is believed to be related to a decreased production of aqueous humor. 

Blockers can be used topically to reduce intraocular pressure in patients with chronic open-angle glaucoma and ocular hypertension. The mechanism by which ocular pressure is reduced appears to depend on decreased production of aqueous humor. Timolol has a somewhat greater ocular hypotensive effect than do the available cholinomimetic or adrenomimetic drugs. The 3-blockers also are beneficial in the treatment of acute angle-closure glaucoma. 

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. 

T.H. Maren, The Development of Ideas Concerning the role of Carbonie Anhydrase in the Secretion of Aqueous Humor Relation to the Treatment of Glaueoma , in Glaucoma Applied Pharmacology in Medical Treatment,. S.M. Drance and A.H. Neufeld, eds., Grune and Stratton, Inc., Orlando, 1984, pp. 325-355. 

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