Muscle direct-acting cholinomimetics

The most prominent pharmacologic effects of cholinesterase inhibitors are on the cardiovascular and gastrointestinal systems, the eye, and the skeletal muscle neuromuscular junction (as described in the Case Study). Because the primary action is to amplify the actions of endogenous acetylcholine, the effects are similar (but not always identical) to the effects of the direct-acting cholinomimetic agonists. 

Cholinesterase inhibitors have less marked effects on vascular smooth muscle and on blood pressure than direct-acting muscarinic agonists. This is because indirect-acting drugs can modify the tone of only those vessels that are innervated by cholinergic nerves and because the net effects on vascular tone may reflect activation of both the parasympathetic and sympathetic nervous systems. The cholinomimetic effect at the smooth muscle effector tissue is minimal since few vascular beds receive cholinergic innervation. Activation of sympathetic ganglia may increase vascular resistance. 

An alkaloid of natural plant origin, pilocarpine is a direct-acting cholinergic agonist with a dominant action at both peripheral and central muscarinic sites. The cholinomimetic action of pilocarpine on smooth muscle muscarinic receptors generally results in contraction.The response of intraocular smooth muscle to pilocarpine is pupillary constriction, spasm of accommodation, and reduction of lOP. 

The cholinomimetics act on the neuromuscular junction (muscarinic), either by directly stimulating the acetylcholine receptors on the smooth muscle ceUs or by increasing the levels of acetylcholine in the neuromuscular junction by blocking cholinesterase activity. Some cholinomimetics, such as bethanechol, can act both at the level of the myenteric plexus (nicotinic) and directly on the intestinal smooth cells. 

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