Figure 5.6. 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, Kaufman PL, Erickson-Lamy K, Polansky JR. Accommodation and ciliary muscle muscarinic receptors after echothiophate. Invest Ophthalmol Vis Sci. 1991;32:3288-3297.

subsensitivity in the ciliary muscle. Functional recovery occurs when agonist treatment is discontinued,50-53 even in the face of permanent anatomic abnormalities in the ciliary muscle and TM.54,55

Corneal toxicity, conjunctival and intraocular vascular congestion, fibrinous iritis (especially in predisposed individuals or following intraocular surgery), retinal detachment (in predisposed individuals), lacrimal canalicular stenosis, posterior sy-nechiae, iris cysts, angle closure, and, most important, cataracts may occur especially with cholinesterase inhibitors.

Systemic toxicity following appropriate topical ocular administration is extremely rare. Theoretically, sensitive individuals may develop sweating and gastrointestinal overactivity following suggested dosage and administration, but this is much more likely to occur with inappropriate dosing and/or in children because of their lower body weight. Overdosage can produce sweating, salivation, nausea, tremors, slowing of the pulse, and a decrease in blood pressure. In moderate overdosage, spontaneous recovery is to be expected and is aided by intravenous fluids to compensate for dehydration. For severe poisoning, atropine is the pharmacologic antagonist to pilocarpine.

Frequency of dosage is an important factor in systemic toxicity. Pure echothio-phate powder should never be applied directly to the eye, because serious systemic poisoning will result.

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