Muscarinics, adverse reaction

The adverse reactions are due to the peripheral muscarinic blockade and central actions. The general side effects include dry mouth, difficulty is swallowing, thirst, dry skin, skin rash, flushed skin etc. It also produces constipation, urinary retention, impotence, difficulty in micturition, tachycardia, palpitation, postural hypotension, dilatation of pupil, photophobia, blurred vision, dizziness, fatigue, anxiety and tremors etc. 

Adverse effects Hi receptor blockers have a low specificity, that is, they interact not only with histamine receptors but also with muscarinic cholinergic receptors, a-adrenergic receptors, and serotonin receptors (see Figure 40.6). The extent of interaction with these receptors and, as a result, the nature of the side effects, vary with the structure of the drug. Some side effects may be undesirable, and others may have therapeutic value. Furthermore, the incidence and severity of adverse reactions varies between individual subjects. 

Tropicamide, like atropine, cyclopentolate, and scopolamine, enters the systemic circulation rapidly. After applying two 40-ml drops of 0.5% tropicamide to one eye in eight patients, peak plasma concentrations were reached in 5 to 30 minutes but were variable (1.3 to 5.2 ng/ml).A mean peak concentration of 2.8 ng/ml was measured at 5 minutes. Despite the rapid systemic absorption, tropicamide has a low affinity for systemic muscarinic receptors.Thus adverse systemic reactions to tropicamide are quite rare. Two studies observed no significant adverse reactions associated with the use of tropicamide in 3,851 drug applications in patients undergoing ophthalmoscopy with either 0.5% or 1% tropicamide.The only reported effects were mild and transient transient changes in lOP on the order of 4 to 12 mm occurred in seven patients, and one individual experienced a transient intermittent esotropia. 

Adverse reactions with antihistamines are the result of multiple mechanisms (see Figure 13-3). Muscarinic, a-adrenergic, and serotonin receptor blockade may result in mydriasis, dry mouth and eyes, urinary retention, constipation, and dizziness in first-generation antihistamines. When the neurotransmitter effect of histamine is interrupted, various CNS adverse reactions may occur. These side effects include increased sedation, decreased cognitive function, decreased psychomotor function, and headache. 

Cardiac function can be impaired by the action of drugs on specific receptors. To deal with every adverse reaction that is mediated via the effects of drugs acting on specific cardiac receptors is beyond the scope of this chapter. Among the most dominant membrane-bound receptors in the cardiac muscle that can contribute to adverse drug reactions are the p-adrenergic and cholinergic (muscarinic) receptors. 

Urinary tract Urinary system adverse reactions, especially enuresis, have been associated with clozapine [SED-15, 832] with an estimated incidence greater than 6%. The mechanisms include overflow incontinence after urinary retention due to the anti-muscarinic action of clozapine or a cholinomimetic activity, and reduced internal urethral sphincter tone caused by aj adrenoceptor blockade enuresis has also been attributed to a non-specific action of clozapine such as excessive sedation, lowering of the seizure threshold, and constipation exacerbating urinary retention and over-fiow. Secondary enuresis in a 21-year man with schizophrenia settled with resolution of his psychotic symptoms but later remerged after starting clozapine [SS ]. 

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