Cholinergic hypersensitivity

Pharmacologic Evaluation. The denervated iris sphincter in Adie s pupil shows cholinergic hypersensitivity. This response is expected according to the principle of denervation hypersensitivity. The hypersensitivity does not seem to correlate with either the amount of sphincter denervation, the duration of the Adie s pupil, or the amount of light-near dissociation. Occasionally, an acute Adie s pupil shows very little hypersensitivity during the first few weeks after onset but gradually becomes increasingly hypersensitive several months after the initial episode. 

Cholinergic hypersensitivity can be tested by using pilocarpine in 0.0625%, 0.1%, 0.125%, or 0.25% solution (Table 22-5).The usefulness of the pilocarpine test in eliciting cholinergic hypersensitivity depends on the presence of a standardized concentration of dmg at the iris. Thus any clinical procedure that compromises the corneal epithelium, the use of wetting agents, or other factors that enhance corneal penetration may result in false-positive findings. 

Symptomatic patients may benefit from the instillation of 0.1% to 0.125% pilocarpine into the affected eye three or four times daily. Because of individual variability, various low concentrations of pilocarpine should be attempted to determine the optimum concentration of miotic that alleviates symptoms as periocular discomfort, headache, photophobia, or blurred vision. If a miotic is used in this fashion, the patient should be carefully monitored in anticipation of modifying the drug regimen if the degree of cholinergic hypersensitivity changes over time. 

If, however, the patient exhibits only a unilateral fixed and dilated pupil without evidence of ptosis or extraocular muscle involvement, the clinician should perform the pilocarpine test, first using a 0.125% solution to reveal any cholinergic hypersensitivity as evidence for Adie s pupil. If there is no local iris damage by slit-lamp examination, no sector palsy of the iris sphincter, and no cholinergic hypersensitivity demonstrated by the 0.125% pilocarpine test, then the condition might be associated with interruption of the preganglionic innervation to the iris sphincter (i.e., third-nerve palsy). If the patient has third-nerve palsy, topically instilled pilocarpine in moderate concentrations activates the muscarinic receptor sites on the iris sphincter. Therefore if 0.125% pilocarpine reveals no cholinergic hypersensitivity, the practitioner... 

These drugp are contraindicated in patients with known hypersensitivity to die drugs, asthma, peptic ulcer disease, coronary artery disease, and hyperthyroidism. Bethanecol is contraindicated in those with mechanical obstruction of die gastrointestinal or genitourinary tracts. Fhtients with secondary glaucoma, iritis, corneal abrasion, or any acute inflammatory disease of the eye should not use die ophtiialmic cholinergic preparations. 

Contraindications Glaucoma, obstructive uropathy, obstructive disease of Gl-anti-cholinergic tract, paralytic ileus, intestinal atony of the elderly or debilitated patient, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis especially if complicated by toxic megacolon, myasthenia gravis, hiatal hernia associated with reflux esophagitis, hypersensitivity to any component of f he formulaf ion, acuf e infermiffenf porphyria. 

Patients with Down syndrome are hypersensitive to topically applied anticholinergic agents. The pupils often dilate widely in response to tropicamide, reflecting an imbalance between cholinergic and adrenergic autonomic activity in the iris. Cyclopentolate, scopolamine, homatropine, and atropine should therefore be avoided in these patients if at all possible. 

Pilocarpine Cholinergic agonist No constriction Constricts an Adie s tonic pupil owing to hypersensitivity... 

Hypersensitivity and Cholinergic Hypofunctlon in the Pathophysiology of Tardive Dyskinesia. Psychophamacol. 34 21-35.. ... 

Irmotecan Nausea and vomiting cholinergic syndrome hypersensitivity reactions anaphylaxis diarrhoea Bone marrow depression diarrhoea colitis ileus alopecia renal impairment teratogenic... 

Must histamine is synthesized and stored in mast cells and basophilic granultKytes. Protein-complexed histamine is then stored in secretory granules and released by exocytosis in le.sponse to a wide variety of immune (antigen and antibody) and nonimmunc (bacterial products, xenobiotics, physical effects, and cholinergic effects) stimuli. The release of histamine as one of the mediators of hypersensitivity reactions is initiated by the interaction of an antigen-IgE com-... 

A possible compensatory cholinergic receptor hypersensitivity occurs, leading in some individuals to dystonic reactions. 

Caution if hypersensitivity to other anticonvulsants risk of cross-sensitivity Caution if absence, atonic, or myoclonic seizures may increase generahzed convulsion frequency Caution if increased intraocular pressure may cause exacerbation due to cholinergic antagonism Caution if hepatic or renal impairment Caution if cardiac disease, or cardiac conduction disturbances increased risk of atrioventricular heart block Caution in SLE... 

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