Ocular pressure

Topical corticosteroids are employed in some cases of bacterial keratitis. The suppression of inflammation may reduce corneal scarring. However, local immunosuppression, increased ocular pressure, and reappearance of the infection are disadvantages to their use. There is no conclusive evidence that they alter clinical outcomes. If the patient is already on topical corticosteroids when the keratitis occurs, discontinue use until the infection is eliminated.19... 

Topical routes of drug administration are where the drug is applied directly to the site of action. Many medicines are applied directly for example, hydrocortisone can be rubbed into the skin to relieve a local area of inflammation. The anticholinesterase neostigmine is dropped directly onto the eye surface to relieve glaucoma, a condition characterised by raised intra-ocular pressure which if untreated can lead to blindness. 

Furthermore, by in vitro experiments, it has been verified that stereospecific activation of alprenoxime is organ-specific, occurring in the eye and not systemically. When administered locally to rabbits, marked decreases in intra-ocular pressure were observed, whereas oral administration elicited almost no cardiac effects. Such ketoximes represent promising chemical delivery systems in the treatment of glaucoma However, a major limitation is their poor stability in solution, seemingly due to hydrolysis of the oxime function. 

Acute abdominal conditions Narcotics may obscure diagnosis or clinical course. Do not give SR morphine to patients with Gl obstruction, particularly paralytic ileus, as there is a risk of the product remaining in the stomach for an extended period and the subsequent release of a bolus of morphine when normal gut motility is restored. Special risk patients Exercise caution in elderly and debilitated patients and in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Also exercise caution in patients sensitive to CNS depressants, including those with cardiovascular disease myxedema convulsive disorders increased ocular pressure acute alcoholism delirium tremens cerebral arteriosclerosis ulcerative... 

Uses Neovascular wet macular degenoation Action Vascular endothelial growth factor inhibitor Dose 0.5 mg intravitreal inj qmo Caution [C ] Hx thromboembohsm Contra Periocular Infxn Disp Inj SE Endophthalmitis, retinal detachment/hemorrhage, cataract, intraocular inflammation, conjunctival hemorrhage, eye pain, floaters EMS None OD Unlikely, but immediate effect would be vision loss and pain d/t t ocular pressure... 

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. 

Calculations performed by Winter [35] showed that the increase in hydrostatic pressure (3-6 Torr) is within the physiological limits and should be well tolerated by the eye (normal intra-ocular pressure 20 Torr). 

All these parameters are very close to the requirements which a long-term ocular endotamponade has to fulfil. Also the in vivo tests in a rabbit eye model were extremely promising no emulsification, no changes in the vascular structure of the retina and no increase of the intra-ocular pressures. All negative side effects, seen with the monomeric FCLs, seemed to be eliminated. In addition, some additional advantages could be claimed reduced tissue penetration and the potential to dissolve drugs [44,45]. 

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. 

At last, the clinical examination of the eye also requires a measurement of the ocular pressure. The comeal ulcer makes this measurement using an... 

Fig. 8.1 Right eye. No light perception. Presurgery aspect. Clear cornea, calm anterior chamber, old posterior synechia, ext-racapsular surgical aphakia. Normal ocular pressure...

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). 

Randall tried every conventional IOP [Intra-Ocular Pressure] medication. Some worked for a time, then diminished in effectiveness. Meanwhile, his ophthalmologist was perplexed by the wide fluctuations in his IOP readings. Randall couldn t bring himself to clear up the mystery. 

Losartan was shown to increase uric acid excretion by inhibiting its tubular reabsorption. This effect does not lie within the spectrum of the blockade of AT, receptors, but rather is a genuine action of the drug on renal tubuli. Losartan was also shown to decrease ocular pressure in normotensive as well as in hypertensive patients with or without glaucoma. Losartan and eprosartan also reduce central sympathetic tone. A metabolite of losartan, EXP-3179 (Fig. 5.8), does not block AT, receptors but may inhibit the atherosclerotic process by suppressing intercellular cell adhesion molecules (ICAM-1), cyclooxygenase-2 (COX-2) and thrombox-ane-A2 (TXA-2). These effects of losartan may lead to potential indications other than blood pressure reduction in hypertensive patients [7]. 

Losartan appears to be unique among the ARBs because it inhibits the urate anion transport in renal proximal tubuli hence, it increases uric acid excretion and decreases plasma levels of uric acid in hypertensive patients. This effect is not the consequence of AT] receptor blockade. Since high uric acid levels have been associated with cardiovascular morbidity/mortality, losartan may be the best ARB for patients with gout [7,30,31]. Moreover, losartan was found to decrease ocular pressure in normotensive as well as in hypertensive patients [32]. 

Today, physostigmine is used only rarely in medicine, as a miotic, which helps to reduce intra-ocular pressure in the glaucomic eye, and as an antidote following the intake of anticholinergic drugs (e.g., atropine and scopolamine). 

Figure 12-3 Weekly intraocular pressure responses of eyes treated with medrysone 1%, fluorometholone 0.1%, and dexamethasone phosphate 0.1%. Each point represents a mean value (mm Hg) of 12 eyes. (Reprinted with permission from Mindel JS, Tovitian HO, Smith H, et al. Comparative ocular pressure elevations of topical corticosteroids. Arch Ophthalmol 1980 98 1578. Copyright 1980, American Medical Association.)...

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. 

Armaly and Rao examined the clinical effects of the Pilocarpine Ocusert systems with different release rates. The systems exhibited a dose-response relationship such that increases in the release rate above 50 pg/h resulted in increased ocular hypotensive effects with no appreciable change in ocular pressure. The reduction in pressure observed at the 50 pg/h rate was comparable with the changes seen after the administration of 4-8% of pilocarpine solutions. 

Armaly, M.F. Rao, K.R. The effect of pilocarpine ocusert with different release rates on ocular pressure. Investigative Opthamol. 1973, 12, 491-493. 

Well-documented acute myopia and increased ocular pressure attributed to aspirin has been described (24). 

Rohr WD. Transitorische Myopisierung und Drucksteigerung als Medikamentennebenwirkung. [Transitory myopia and increased ocular pressure as side effects of drugs.] Fortschr Ophthalmol 1984 81(2) 199-200. 

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). 

Dear GD, Hammerton M, Hatch DJ, Taylor D. Anaesthesia and intra-ocular pressure in young children. A study of three different techniques of anaesthesia. Anaesthesia 1987 42(3) 259-65. 

Feneck RO, Cook JH. Failure of diazepam to prevent the suxamethonium-induced rise in intra-ocular pressure. Anaesthesia 1983 38(2) 120-7. 

Grover VK, Lata K, Sharma S, Kaushik S, Gupta A. Efficacy of lignocaine in the suppression of the intra-ocular pressure response to suxamethonium and tracheal intubation. Anaesthesia 1989 44(l) 22-5. 

Edmondson L, Lindsay SL, Lanigan LP, Woods M, Chew HE. Intra-ocular pressure changes during rapid sequence induction of anaesthesia. A comparison between thiopentone and suxamethonium and thiopentone and atracurium. Anaesthesia 1988 43(12) 1005-10. 

As of 17 August 2001 there were 23 reported cases (22 adults and 1 child) out of 825 000 patients. Symptoms typically occur within the first month of therapy, and the patients report acutely reduced visual acuity and/or ocular pain. There is myopia, redness, swelling of the anterior chamber, and raised ocular pressure, with or without pupil dilatation. Supraciliary effusion can displace the lens and iris anteriorly, secondarily causing angle-closure glaucoma. The symptoms are reversible if topiramate is withdrawn. Acute myopia has been described as a rare idiosyncratic reaction to other sulfonamides. It has been postulated that the pathogenic mechanism is related to partial inhibition of carbonic anhydrase and to ciliary body swelling. 

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.

Glaucoma is a disorder of vision accompanied by an increase in ocular pressure. Although mostly replaced by other drugs (e.g., beta blockers and pilocarpine), anti-ChE drugs such as ecothiopate are still used in the treatment of these common disorders. 

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