Ocular pressure lowering

The ocular pressure-lowering effect of latanoprost appears to be additive with timolol, with mild transient hyperemia in 50% of those treated with latanoprost alone (70). 

Topical PGE2 and PGF201 significantly reduce intraocular pressure for at least 24 hours and are used in the treatment of glaucoma. Derivatives of the isopropyl ester of PGp2a appear to be the most effective. Transient ocular adverse effects include conjunctival hyperemia, local irritation, intermittent photophobia, and pain in the eye (66-68). Newer derivatives, such as latanoprost, travoprost, and bimatoprost, appear to be better tolerated, with less severe and less frequent adverse effects (69). They reduce intraocular pressure by increasing uveoscleral outflow. The ocular pressure-lowering effect of latanoprost appears to be additive with timolol, with mild transient hyperemia in 50% of those treated with latanoprost alone (70). 

There are several types of -class CAs i.e., a-CA I-VII, reported in the literature, out of which the human carbonic anhydrase II (HCA II), the most extensively studied carbonic anhydrase, has an exceptionally high CO2 hydration rate and a wide tissue distribution 107). The HCA II comprises a single polypeptide chain with a molecular mass of 29.3 kDa and contains one catalytic zinc ion, coordinated to three histidine residues, His 94, His 96, and His 119. A tetrahedral coordination geometry around the metal center is completed with a water molecule, which forms a hydroxide ion with a pK value of 7.0 108). Quigley and co-workers 109,110) reported that the inhibition of the synthesis of HCO3 from CO2 and OH- reduces aqueous humor formation and lowers intra-ocular pressure, which is a major risk factor for primary open-angle glaucoma. 

Burgalassi, S., Chetoni, P., Panichi, L., Boldrini, E. and Saettone, M.F. (2000b) Xyloglucan as a novel vehicle for timolol pharmacokinetics and pressure lowering activity in rabbits. Journal of Ocular Pharmacology and Therapeutics 16(6), 497-509. 

A masked study using male volimteers compared ocular pressure elevations with dexamethasone phosphate 0.1%, fluorometholone alcohol 0.1%, and medrysone 1% applied four times daily for 6 weeks. Figure 12-3 shows the relative ability of these steroids to raise lOP. At the end of 6 weeks of treatment, the mean pressure increases fiar dexamethasone, fluorometholone, and medrysone were 63.1%, 33.8%, and 8.3%, respectively. Additional studies have compared the effects of fluorometholone alcohol suspension 0.25% with dexamethasone sodium phosphate solution 0.1% in steroid-responsive patients. Subjects received the medication in one eye four times daily for up to 6 weeks. Although both drugs elevated lOP, mean pressure increases from baseline in eyes treated with fluorometholone were significantly lower than those in eyes treated with dexamethasone at weeks 2,4, and 6. Further studies are needed to compare the effects of the alcohol and acetate derivatives of fluorometholone on lOP in both nonsteroid and steroid responders. 

Ocular distribution and elimination of biodegradable polyalkylcyanoacrylate nanoparticles has been examined in a number of reports. " " Pilocarpine containing polybutylcyanoacrylate nanoparticles alone or in gel type formulations are capable of enhancing and prolonging the miosis and pressure lowering response in various animal models. ... 

Figure 28-1 Dorzolamide (Trusopt). the first FDA-approved drug to be designed by structure-based methods, is a carbonic anhydrase inhibitor that is used to lower ocular pressure in glaucoma patients.

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... 

In clinical studies the Oeuserl system has been shown to lower intra-ocular pressure, the main (and sight threatening) symptom of glaucoma, for periods up to one week (a.47). Furthermore, there were fewer side effects associated with this system and patient compliance was improved in comparison with the conventional pilocarpine eye drop formulation. One disadvantage of the Ocusert system was the discomfort to some patients and potential retention problems within the eye (a.43). 

If the same test for intra-ocular pressure change is performed on a sample of individuals with open angle hypertensive glaucoma, a trimodal distribution of phenotypes is also obtained but the frequency of the P P genotype is much lower than in a randomly selected population. 

Sympathomimetics are used to produce mydriasis for ophthalmoscopic evaluation mydriasis is not maximal, as with the anticholinergic mydriatics, but especially in younger patients sympathomimetic mydriasis proves quite effective and causes little or no reduction in accommodation. Sympathomimetic agents are also used as vasoconstrictors in surgical procedures, for symptomatic relief or allergic reactions and hyperaemia of the conjunctiva, and to lower intra-ocular pressure in glaucoma. 

Intraocular pressure (lOP) To lower lOP in patients with open-angle glaucoma or ocular hypertension. 

Elevated intraocular pressure (lOP) For reduction of elevated lOP in patients with open-angle glaucoma and ocular hypertension who are intolerant of other lOP-lowering medications or insufficiently responsive to another lOP-lowering medication. 

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. 

The cannabinoids tested so far appear to be of limited use in the treatment of glaucoma. They appear to act only against a primary (but not sole) symptom of the disease (i.e., ocular hypertension), rather than against the underlying disease process, which remains uncertain. The side-effects of those cannabinoids particularly effective in lowering intraocular pressure (IOP) restrict their clinical usefulness (with some exceptions such as canna-bigerol). Cannabinoids administered intraocularly to humans cause no IOP reduction. ... 

So far, there is only one microparticulate ocular delivery system on the market. Betoptic S is obtained by binding of betaxolol to ion exchange resin particles. Betop-tic S 0.25% was found to be bioequivalent to the Betoptic 0.5% solution in lowering the intraocular pressure [208],... 

Like fluorometholone, medrysone is a synthetic derivative of progesterone. As compared with prednisolone, dexamethasone, and fluorometholone, medrysone exhibits limited corneal penetration and a lower affinity for glucocorticoid receptors. In clinical use it appears to be the weakest of the available ophthalmic steroids. Medrysone can be useful for superficial ocular inflammations, including allergic and atopic conjunctivitis, but intraocular inflammatory conditions generally do not respond. Clinical experience with medrysone has also indicated that it is less likely to cause a significant rise in lOP. However, caution needs to be exercised in patients known to respond to steroids with a rise in lOP (so-called steroid responders), because pressure increases can lead to ocular damage. 

---