P6E1 Disease Interactions

The use of miotic agents may occasionally cause retinal detachment due to drug-induced ciliary or accommodative spasm, which causes the lens and vitreous to move forward and create a retinal tear. Therapy with miotic agents should be administered with extreme caution, if at all, in patients with risk factors for retinal detachment, such as old age, retinal degenerative changes or other retinal disorders, aphakia, prior cataract extraction, or a history of severe myopia or retinal detachment.

The use of miotic agents is contraindicated in patients with active anterior uveitis and/or glaucoma associated with iridocyclitis. Pupillary constriction produced by these agents may aggravate the inflammation and predispose these patients to the development of posterior synechiae.

Up to 30% of aphakic patients treated chronically with ophthalmic epinephrine (of which dipivefrin is a prodrug) may develop cystoid macular edema, which is generally reversible following withdrawal of the medication. Ophthalmic epinephrine preparations should be administered cautiously with appropriate monitoring in patients with aphakia. Therapy should be discontinued if blurred or distorted vision, central scotoma, and/or loss of visual acuity occur. Slight visual impairment may respond to a reduction in the concentration or frequency of administration of the drug.

Topically applied epinephrine is systemically absorbed, with the potential for producing clinically significant systemic effects. In cardiac tissues, epinephrine produces positive chronotropic and inotropic effects via stimulation of beta-1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart are increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, extrasystoles, arrhythmia and hypertension have been reported rarely during the use of ophthalmic epinephrine products, but may be more likely if the corneal epithelium is damaged or permeability is increased by tonometry, surgery, inflammation, or topical application of a local anesthetic. Therapy with ophthalmic epinephrine should be administered cautiously in patients with corneal abrasion, sensitivity to sympathomimetic amines, hyperthyroidism or underlying cardiovascular or cerebrovascular disorders, especially coronary insufficiency, cardiac arrhythmia, or hypertension. Dipivefrin, a prodrug of epinephrine, is associated with considerably fewer and milder local and systemic adverse effects and may be preferable in some of these patients.

The use of ophthalmic preparations of epinephrine, including dipivefrin (a prodrug of epinephrine), is contraindicated in patients with narrow-angle glaucoma or anatomically narrow angles. These agents stimulate both alpha-1 and alpha-2 adrenergic receptors, thus topical administration can induce transient mydriasis, either with or without the use of concomitant miotic agents. In patients with narrow angles, any degree of pupillary dilation can provoke an acute attack of angle-closure glaucoma. In contrast, sympathomimetic agents with relative alpha-2 adrenergic selectivity such as apraclonidine and brimonidine produce little to no mydriasis at normally recommended dosages.

The use of miotic agents has been associated with the development of lens opacities characterized by the appearance of anterior subcapsular vacuoles. The incidence of cataracts appears to be highest in patients treated with long-acting cholinesterase inhibitors (e.g., demecarium and echothiophate) and may also be related to age (higher in patients > 60 years of age), drug concentration, frequency of use, and duration of therapy (>= 6 months). Lens opacities usually regress if miotic therapy is withdrawn early in their development but often become progressive once they are established. Therapy with miotic agents should be administered cautiously in patients with or predisposed to cataracts. Slit-lamp examinations should be performed regularly, and miotic therapy discontinued if necessary.

Topically applied cholinergic agents are systemically absorbed, with the potential for producing rare but clinically significant systemic effects, including urinary incontinence, tightness of the bladder, increased gastric contractility and acid secretion, bradycardia, severe hypotension, bronchospasm, seizures, and coma. Increases in blood pressure may occur rarely due to a nicotinic effect on sympathetic ganglia. Therapy with ophthalmic cholinergic agents, particularly the long-acting cholinesterase inhibitors (e.g., demecarium and echothiophate), should be administered cautiously in patients with corneal abrasion (which may increase drug penetration), bronchospastic diseases, spastic gastrointestinal disturbances, urinary tract obstruction, peptic ulcer, pronounced bradycardia and hypotension, vascular hypertension, acute cardiac failure, recent myocardial infarction, epilepsy, parkinsonism, and other conditions that may respond adversely to vagotonic effects. The usual precautions should be followed to minimize the risk of systemic toxicity, including digital compression of the nasolacrimal ducts (1 to 2 minutes) following instillation to limit drainage into the nasal chamber, where extensive absorption may occur, and washing hands after use to prevent skin absorption. Excessive cholinergic effects may be reversed with parenterally administered atropine.

Topically applied epinephrine is systemically absorbed, with the potential for producing clinically significant systemic effects. In patients with prostatic hypertrophy, urinary difficulty may develop or worsen due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with ophthalmic epinephrine products should be administered cautiously in patients with prostate enlargement. Dipivefrin, a prodrug of epinephrine, is associated with considerably fewer and milder local and systemic adverse effects and may be preferable in some of these patients.

Topically applied sympathomimetic agents are systemically absorbed, particularly during prolonged or indiscriminate use. Slight increases in blood glucose concentrations may occur with the use of these drugs. Therapy with topical sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. It is important that the recommended dosages of the individual products not be exceeded.