Cholinergic stimulants direct-acting

FIGURE 19-1 T Mechanism of action of cholinergic stimulants. Direct-acting stimulants bind directly to the postsynaptic cholinergic receptor. Indirect-acting stimulants inhibit the cholinesterase enzyme, thus allowing acetylcholine to remain in the synaptic cleft. 

Pharmacology Direct-acting miotics are parasympathomimetic (cholinergic) drugs which duplicate the muscarinic effects of acetylcholine. When applied topically, these drugs produce pupillary constriction, stimulate ciliary muscles, and increase aqueous humor outflow facility. With the increase in outflow facility, there is a decrease in lOP. Topical ophthalmic instillation of acetylcholine causes no discernible P.1248... 

Increased stimulation of the AChR can be achieved in two ways (1) by binding of the directly acting cholinergic agonists to the AChR, triggering nicotinic or muscarinic... 

Direct-acting stimulants bind directly to the cholinergic receptor to activate it, which in turn initiates a cellular response. These stimulants may be considered... 

Unlike the systemic direct-acting cholinergic stimulants (e.g., bethanechol), cholinesterase inhibitors display a relative lack of specificity regarding which cholinergic synapses they stimulate. These drugs tend to inhibit the acetylcholinesterase found at... 

It is a direct acting muscarinic agonist and acts by competitive stimulation of the muscarinic cholinergic receptor. 

Dopamine acts on G-protein-coupled receptors belonging to the D1 -family of receptors (so-called D1-like receptors , or DlLRs, comprised of Dl- and D5-receptors), and the D2-family of receptors ( D2-like receptors , or D2LRs comprised of D2-, D3- and D4-receptors). Dl LRs stimulate adenylate cyclase activity and, possibly, also phosphoinosit-ide hydrolysis, while D2LRs reduce adenylate cyclase activity. In the striatum, DlLRs are predominately associated with medium spiny neurons of the direct pathway, while D2LRs have been found as autoreceptors on dopaminergic terminals, as heteroreceptors on cholinergic interneurons, and on indirect pathway neurons. In the SNr, DlLRs are located on terminals of the direct pathway projection, while D2LRs appear to function as autoreceptors. 

Succinylcholine acts primarily at the skeletal neuromuscular junction and has little effect at autonomic ganglia or at postganglionic cholinergic (muscarinic) junctions. Actions at these sites attributed to succinylcholine may arise from the effects of choline. Succinylcholine has no direct action on the uterus or other smooth muscle structures. It does not enter the CNS and does not cross the placental barrier. It may, however, release histamine from mast cells. Because succinylcholine works by stimulating rather than blocking end plate receptors, anti-AChEs will not reverse muscle paralysis and may actually prolong the block. 

FIGURE 13-18. Pharmacology of nicotine (part 1). Nicotine acts directly on nicotinic cholinergic receptors, which are themselves located in part on mesolimbic dopamine neurons. When nicotine stimulates these receptors (A and B), it causes release of dopamine from the mesolimbic neurons and thereby conveys a sense of reward and pleasure. 

Cholinergic medication (cholinesterase inhibitors, anticholinesterase) has either a direct- or indirect-acting effect on receptor sites. Direct and indirect effects inhibit the action of the enzyme cholinesterase (acetylcholinesterase). By inhibiting cholinesterase, more acetylcholine is available to stimulate the receptor and remains in contact with the receptor longer. 

Acts directly at cholinergic receptor of smooth muscle of urinary bladder and GI tract. Increases tone of detrusor muscle, may initiate micturation (urination), bladder emptying. Stimulates gastric intestinal motility. 

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