Mechanism Of Action

The primary mechanism by which most PGs reduce IOP is by increasing outflow, especially through the uveoscleral outflow pathway (figure 2.2). Numerous animal and human studies have confirmed this mechanism of action.11,12 In several studies, PGs have been demonstrated to increase outflow facility.12-17 PGs do not reduce aqueous production. The mechanism by which PGs increase uveoscleral outflow is continuing to be elucidated. One mechanism may be the relaxation of the ciliary muscle. This is...

Drugs For Systemic Hypertension

Beta blockers are widely used in the management of cardiovascular disorders, including hypertension, angina pectoris, and cardiac arrhythmias. These drugs decrease the heart rate and the cardiac output, decrease blood pressure, and can decrease IOP. Although thiazide-type diuretics are used as initial therapy for most patients with hypertension, beta blockers are commonly used for stage 2 hypertension or other compelling indications.1 Systemic hypertension and...

Info

Data from Physicians' Desk Reference for Ophthalmic Medicines, 34th edition, 2006. Data from Physicians' Desk Reference for Ophthalmic Medicines, 34th edition, 2006. topical timolol has occasionally been associated with more serious ocular surface disease such as cicatricial pemphigoid.23 Allergic blepharoconjunctivitis develops in about 3 of patients using OBBs.24 Transient blurred vision following administration is a common adverse side effect associated with OBBs. With timolol gel-forming...

References

Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol. 1982 26 207-218. 2. Plazonnet B, Grove J, Durr M, et al. Pharmacokinetics and biopharmaceutical aspects of some anti-glaucoma drugs. In Saettone MF, Bucci M, Speiser P, eds. Ophthalmic Drug Delivery Biopharmaceutical, Technological, and Clinical Aspects. New York Springer-Verlag 1987 117-119. 3. Wagner JG. Kinetics of pharmacologic response, I proposed relationships between response and drug concentration in the...

American Academy of Ophthalmology Clinical Education Secretariat Louis B Cantor MD Indiana University School of

Retinal Detachment Principles and Practice, third edition Daniel A. Brinton and Charles P. Wilkinson 2. Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway, second edition Gerald Allen Fishman, David G. Birch, Graham E. Holder, and Mitchell G. Brigell 3. Visual Fields Examination and Interpretation, second edition Thomas J. Walsh 4. Glaucoma Surgery Principles and Techniques, second edition Edited by Robert N. Weinreb and Richard P. Mills 5. Fluorescein and...

Peter A Netland

Hypertensive drugs are commonly prescribed medications that may affect intraocular pressure (IOP). Although not prescribed by physicians, alcohol and marijuana are frequently self-administered substances that may also affect IOP. This chapter is not intended as an exhaustive review of the effects of all systemically administered drugs on the eye, but instead focuses on drugs widely used in the general population that can influence IOP. The potential effect of systemic drugs on IOP may be...

Trauma And Glaucoma

Elevated IOP associated with hyphema usually responds favorably to aqueous suppressants. CAIs may also be added to the treatment regimen. However, caution is warranted with systemic acetazolamide in patients with sickle cell hemoglobinopathy (or sickle trait), because the drug increases the concentration of ascorbic acid in the aqueous, which leads to more sickling in the anterior chamber.53 Systemic acetazolamide also causes systemic acidosis, which may exacerbate eryth-rocyte...

Drug Interactions

Drugs that may compromise renal or cardiovascular status should be used with caution in combination with osmotic drugs. Systemic absorption of topically administered beta blocker, for example, may further compromise patients at risk for congestive heart failure, predisposing them to untoward effects due to osmotic drugs. Osmotic diuretic drugs given to patients receiving angiotensin-converting enzyme inhibitors or other drugs for the treatment of high blood pressure may produce systemic...

Clinical

Although osmotic drugs are not useful in the long-term medical management of chronic glaucoma, they may be invaluable in the therapy of acutely elevated IOP and in the perioperative treatment of certain glaucoma patients.15,21-23 8.7.1 Angle-Closure Glaucoma. The therapy of acute angle-closure glaucoma is directed at lowering IOP and opening the anterior chamber angle. Osmotic drugs are one of the mainstays in the treatment of angle-closure glaucoma because they not only lower IOP but also...

A

Ciliary muscle muscarinic receptor content at various times after discontinuing 2 weeks of twice-daily unilateral topical echothiophate iodide. Bmax for each animal is expressed as the ratio of treated (T) eye to control (C) eye B binding blue line represents least-squares linear regression R (correlation coefficient) 0.76 P (probability that R 0) 0.002. Green line represents T C 1.0, that is, equal Bmax values in treated eye and control eye. Redrawn with permission from Croft MA,...

Modern Fixed Combinations Approved Outside The United States

In recent years, fixed combinations of commonly paired drugs have not received FDA approval due to insufficient additional demonstrated efficacy when compared to their components, despite such potential benefits as improved convenience and compliance and reduced cost to patients. Although the additive effects of pros-taglandins to beta blockers have been demonstrated in several studies,29-31 fewer data exist about the efficacy of adding beta blockers for subjects already on pros-taglandins....

Glaucoma Medical Therapy During Lactation

There are few studies in the literature regarding the safety of glaucoma mediations during breast-feeding. Any medication with any degree of systemic absorption must be assumed to have a measurable level in breast milk. Due to the extreme reluctance to used any medications in pregnant and lactating women, these data are difficult to Pregnancy and Pediatric Patients 235 Table 13.1 FDA Category Classifications for Glaucoma Medications Beta blockers Class C Alpha-adrenergic agonists Carbonate...

Glaucoma Medical Therapy In Pediatric Patients

Children are more vulnerable to side effects, due to reduced body mass and blood volume for drug distribution (resulting in higher concentrations from the same absorbed dose). Also, they may be unable to verbally describe side effects caused by medications. Thus, children on chronic medical therapy need to be carefully monitored. The medical regimen must be frequently reevaluated in an effort to use the minimum medical regimen that will result in acceptable IOP...

Conclusion

Adrenergic agents lower IOP primarily through their alpha-2 stimulation, which lowers adenylate cyclase activity and reduces intracellular cAMP levels. Secondary mediators may include prostaglandins, but topical nonsteroidal anti-inflammatory drugs do not interfere with the efficacy of adrenergic agents in humans. Epinephrine, a nonspecific adrenergic agonist, increases aqueous flow and may raise IOP transiently, but long-term use lowers IOP and is additive to acetazolamide and pilocarpine....

Drugdisease Interactions

The potential CNS adverse effects of OBBs are discussed in section3.6.3. In patients with subtle changes in mental status, OBBs may contribute to symptoms. This effect is reversible with discontinuation of OBBs. Depression, a common condition, is also commonly listed as a CNS adverse effect of beta blockers. Most of the data propagating the notion that beta blockers cause depression emanate from individual case reports or short case series in the late 1960s and 1970s. In contrast, there are at...

Specific Ocular Beta Blockers

In the United States, five topical OBBs have been approved for lowering IOP. These compounds are similar, although there are some differences among the individual compounds and their activity and pharmaceutics. Figure 3.1 depicts the chemical structures of these OBBs, and table 3.1 summarizes them. 3.9.1.1 Timolol solution is available as timolol maleate 0.25 and 0.5 (Timoptic, Istalol) and as timolol hemihydrate 0.5 (Betimol). A timolol maleate gel-forming solution 0.25 and 0.5 is also...

Discrete Openangle Glaucomas

The term ''primary open-angle glaucoma'' refers to a condition characterized by elevated IOP and characteristic optic disk and or visual field damage with no other identifiable cause at slit-lamp examination. However, the use of the word ''primary'' is suggestive of a single, discrete entity with a specific mechanism of disease causation. More likely, this category represents an assortment of disorders, as we are now seeing with the discovery of multiple genetic loci. Similarly, the term...

Glaucoma Medical Therapy In Pregnancy

Although glaucoma is infrequently diagnosed in pregnant patients, occasionally patients with preexisting glaucoma become pregnant. Whenever medications are prescribed for glaucoma, the clinician considers the potential for systemic effects on the patient. In pregnant women, this concern extends to the developing child, as well. One major advantage to the use of topical medications for glaucoma is the reduced systemic absorption and coincident decrease in systemic...

Iop Reduction In Clinical Trials

Numerous clinical trials have demonstrated the efficacy of PG analogs in lowering IOP. Clinical trials with latanoprost,1'2'29'31'47'81 bimatoprost'1'2'44'48 and travo-prost1-3'49 have all shown that these drugs given once daily are more effective than timolol 0.5 given twice a day in reducing mean diurnal IOP in patients with ocular hypertension or glaucoma (figure 2.5). PGs have also been shown to be as effective or more effective and often better tolerated than other topical glaucoma Figure...

Clinical Studies On Additivity

Because PG analogs have a different mechanism of action than other ocular hypo-tensive drugs, the IOP reduction from PGs can be expected to be additive to that of other glaucoma medications. Multiple clinical studies have demonstrated that the effect of PGs is additive to the effect of other ocular hypotensive agents, including timolol, pilocarpine, topical and oral carbonic anhydrase inhibitors (CAIs), alpha-2 agonists, and dipivefrin91-98 and when used in patients on otherwise maximally...

Additivity Of Medications

How well two or more medications achieve IOP reduction also depends upon drug class, or their mechanisms of action. Two beta blockers used together will have little added IOP-lowering effect, since they both decrease aqueous humor formation by the same mechanism. Likewise, two PAs used simultaneously will add little to IOP lowering and, in fact, may be less effective than either medication alone.5 On the other hand, a beta blocker and a CAI both decrease aqueous humor production, but by...

Contraindications

Cholinergic agonists, such as pilocarpine and carbachol, should be avoided in conditions where pupillary constriction and intraocular vascular congestion are undesirable, such as in acute iritis or visually significant lens changes. These agents should also be avoided where there is a history of, or predisposition to, retinal detachment, or a proven sensitivity to these agents, or, for the membrane delivery dosage form, the presence of acute infectious conjunctivitis or keratitis. Patients with...

Initial Medical Management

Once a decision has been made to pursue medical therapy, the ophthalmologist must choose among the many medical options available. Prior to selecting a medication, the physician should review the patient's medical history, allergies, and experience with previous glaucoma medications. Documenting efficacy and side effects of medications previously used in a dedicated location in the medical record will reduce the likelihood of repeating unsuccessful therapeutic trials in the future. Beta...

Other Special Situations

Initial surgical treatment should not be delayed in an attempt to achieve medical control of IOP in infants with congenital glaucoma. Medications are primarily used preoperatively to allow corneal edema to clear, improving visualization at the time of examination under anesthesia and surgery, and to help control any damage that might occur in the interim preoperatively (see also Chapter 13). If trabeculotomies and or goniotomies fail and trabeculectomy is believed...

Target Intraocular Pressure

After the decision to treat has been made, a treatment goal must be set. Glaucoma medications lower IOP, but how low should the IOP be Target IOP is defined as the IOP that is expected to confer optic nerve stability in a patient with glaucoma. Once the target IOP is reached, ideally the rate of ganglion cell loss is lowered to that of age-matched controls or it will be lowered to a rate at which patients will not become visually handicapped during their lifetime. Moorfields Primary Treatment...

Adrenergic Physiology In The

The effects of adrenergic stimulation in the eye are mediated by cell-specific transmembrane receptors, which activate a regulatory guanine nucleotide-binding enzyme, or G-protein, and thereby activate various second-messenger systems in the cell. Three main adrenergic-receptor types are recognized alpha-1, alpha-2, and beta. Each is associated with at least one unique regulatory G-protein Gq, Gi, and Gs, respectively. Numerous additional receptor subtypes have been identified by a unique...

High Iop On Initial Presentation

Patients presenting with extremely elevated IOP (e.g., > 50 mm Hg) usually have symptoms. Unlike the chronically elevated IOP found with primary open-angle glaucoma or some forms of secondary glaucoma, acutely elevated IOP can cause blurry vision, pain, haloes around lights, nausea, vomiting, red eye, and corneal swelling.21 On the other hand, optic nerve or visual field damage is less frequently found with acutely elevated IOP, because the symptoms bring attention to the disorder early on....

Alphaselective Agonists

The alpha-selective agonists available clinically include clonidine, apraclonidine, and brimonidine. Key differences between these agents include therapeutic index, clinical safety, penetration, level of alpha-2 selectivity, and side effects. Clonidine was the first relatively selective alpha-2 agonist available it lowers IOP well, but its narrow therapeutic index, particularly its propensity to cause sedation and systemic hypotension, has made it unpopular in glaucoma therapy. Apraclonidine...

Reasons For Noncompliance

Each mentally and physically competent patient has ultimate responsibility for compliance, but how a patient arrives at the decision to comply or not to comply with medical treatment is based on many factors. A patient's beliefs about health and disease, influenced by personal, societal, cultural, and financial factors, as well as the amount of information he or she has about the disease, play a significant role in this decision. In addition, other factors, such as the nature of the disease,...

Nonselective Agonists

Some brands of the nonselective agonists epinephrine and dipivefrin are listed in table 4.2. 4.3.1 Epinephrine. Epinephrine, a mixed alpha- and beta-adrenergic agonist, was the first topical adrenergic agent used to lower IOP in patients with open-angle glaucoma. Topical administration of epinephrine causes alpha-1-adrenoreceptor-induced conjunctival vasoconstriction, which manifests as blanching, and slight mydriasis. The mydriatic effect can be used to advantage during cataract surgery, where...

Products Of Historical Interest

Adrenergic and cholinergic combinations were reported as early as the 1960s.6'7 The first available combination of IOP-lowering agents was a mixture of pilocarpine and epinephrine. This product evolved during the period when these two classes represented available glaucoma medications, and with additive properties in combination.8'9 Many patients were receiving both in separate bottles, and combining them in a single bottle offered dosing convenience. Some...

S175

Latanoprost-induced iris color darkening a case report with long-term follow-up. J Glaucoma. 2000 9 95-98. Yamamoto T, Kitazawa Y. Iris-color change developed after topical isopropyl unoprostone treatment. J Glaucoma. 1997 6 430-432. Zhan GL, Toris CB, Meza JL, Camras CB. Unoprostone isopropyl ester darkens iris color in pigmented rabbits with sympathetic denervation. J Glaucoma. 2003 12 383-389. Albert DM, Gangnon RE, Zimbric ML, et al. A study of iridectomy...

Glaucoma Treatment Trials

Treatment of POAG and other forms of open-angle glaucoma has been addressed by several large clinical trials comparing medical, laser, and surgical intervention. Two of these trials assessed early surgical intervention. In the Scottish Glaucoma Trial,20 99 patients with newly diagnosed glaucoma were randomly assigned to initial trabeculectomy (46 patients) or conventional medical therapy followed by trabeculectomy if medical therapy failed (53 patients). After a 3- to 5-year follow-up, a...

Bioavailability In Ocular Compartments

The pharmacokinetics of a drug can be mathematically modeled using a technique called compartmental analysis to develop descriptive and predictive information about a drug's concentration at different times in different locations.4 A compartment is an anatomic or physiologic space within an organ that is separated by a barrier to drug transfer (figure 1.1). The drug is assumed to be homogeneously distributed within a compartment, and exchange of the drug between adjacent compartments occurs at...

Ocular Use Of Steroids

Most of the known effects of the glucocorticoids are mediated by widely distributed glucocorticoid receptors. Glucocorticoid enters a target cell as a free molecule. In the absence of the hormonal ligand, intracellular glucocorticoid receptors bound to stabilizing proteins are incapable of activating transcription. When a molecule of glucocorticoid binds to the receptor, the complex undergoes conformational changes that allow it to dissociate from the stabilizing...

Angleclosure Glaucoma

Angle closure is an anatomic disorder comprising a final common pathway of iris apposition to the trabecular meshwork. By recent convention, the term glaucoma is applied to eyes with visual field and or optic nerve damage, analogous to the differentiation between ocular hypertension and glaucoma in eyes with open angles. Angle closure results from various abnormal relationships of anterior segment structures. These, in turn, result from one or more abnormalities in the relative or absolute...

Drug Delivery Systems

Ocusert Pilo System

Commonly used ophthalmic drug formulations, such as solutions, gels, suspensions, and ointments, deliver drugs at rates that follow first-order kinetics, in which the concentration of the drug transferred to the eye decreases exponentially with time. To achieve a constant concentration of the drug in the precorneal tear film and create a steady-state concentration in the tissues, an ophthalmic drug delivery system needs to be designed to deliver a specific drug at a zero-order kinetic rate. At...