Chapter six BASIC PHARMACOLOGYOF THE DIRECT-ACTING CHOLINOCEPTOR STIMULANTS

The direct-acting cholinomimetic drugs can be divided on the basis of chemical structure into esters of choline (including acetylcholine) and alkaloids (such as muscarine and nicotine). A few of these drugs are highly selective for the muscarinic or for the nicotinic receptor. Many have effects on both receptors; acetylcholine is typical.

Cholinomimetic drugs classify cholinomimetic drugs Cholinoceptor stimulants M、NR agonist Acetylcholine,ACH MR agonist Pilocarpine NR agonist nicotine cholinesterase inhibitors Neostigmine physostigmine

M,N receptor agonist acetylcholine 乙酰胆碱 Pharmacological effects 1 Muscarinic effect 1)cardiovascular system:inhibition decrease in heart rate (negative chronotropy) decrease in heart contractility (negative inotropy) decrease in heart conduction velocity (negative dromotropy) reduction in peripheral vascular resistance blood vessels (arteries and veins) dilation (via EDRF)

Acetylcholin乙酰胆碱 Muscarinic effects 2)eye: miosis, accommodation of focus for near vision 3)glands secretion increase sweat, salivary, lacrimal, nasopharyngeal 4)smooth muscle : contraction bronchial muscle ,gastrointestinal tract , urinary bladder detrusor (voiding)

M,N receptor agonist acetylcholine 乙酰胆碱 2 nicotinic effect to excite ganglia adrenal medulla secrete Adr cardiovascular system ↑ smooth muscle ↑ glands secretion ↑ neuromuscular junction ↑

Carbamylcholine (carbachol) M,N receptor agonist similar to ACH

M R agonist—Pilocarpine 毛果芸香碱 active ingredient of poisonous mushrooms Pharmacological effects direct agonist selectively stimulate muscarinic receptors

M R agonist Pilocarpine 1 eye: miosis : sphincter muscle of iris (circular pupillary constrictor muscle) contraction , reduction in pupil size

M R agonist---Pilocarpine 毛果芸香碱

accommodation of focus for near vision :ciliary muscle contraction

reduce intraocular pressure :Ciliary muscle contraction puts tension on the trabecular meshwork, opening its pores and facilitating outflow of the aqueous humor into the canal of Schlemn, increased outflow reduces intraocular pressure

2 Glands secretion increase sweat, salivary, lacrimal, nasopharyngeal

M R agonist---Pilocarpine 毛果芸香碱 Clinical uses 1 glaucoma angle-closure glaucoma type open-angle glaucoma type 2 iritis together with mydriasis drugs (such as antimuscarinic drugs)，to prevent synechia (adhesion) of iris and lens 3 artropine intoxication

M R agonist---Pilocarpine 毛果芸香碱 toxicity 1 Ciliary convulsion (spasm): drops overdosage 2 Depending on absorption: predictable signs of muscarinic excess ( nausea, vomiting, diarrhea, salivation, sweating, cutaneous vasodilation, and bronchial constriction) prevention: press the canthus of the eye beside the nose