Chapter sixChapter 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 drugCholinomimetic drugsclassify cholinomimetic drugs

Cholinoceptor stimulants

M 、 NR agonist Acetylcholine,ACH

MR agonist Pilocarpine

NR agonist nicotine

cholinesterase inhibitors Neostigmine physostigmine

M,NM,N receptor agonist receptor agonist acetylcholine acetylcholine 乙酰胆碱乙酰胆碱

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)

AcetylcholinAcetylcholin 乙酰胆碱乙酰胆碱Muscarinic effectsMuscarinic 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,NM,N receptor agonist receptor agonist acetylcholine acetylcholine 乙酰胆碱乙酰胆碱

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—PilocarpineM R agonist—Pilocarpine 毛果芸香碱毛果芸香碱

active ingredient of poisonous mushrooms

Pharmacological effects

direct agonist

selectively stimulate muscarinic receptors

M R agonistM R agonistPilocarpinePilocarpine

1 eye:

miosis : sphincter muscle of iris (circular pupillary constrictor muscle) contraction , reduction in pupil size

M R agonist---Pilocarpine M R agonist---Pilocarpine 毛果芸香碱毛果芸香碱

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 M R agonist---Pilocarpine 毛果芸香碱毛果芸香碱

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 M R agonist---Pilocarpine 毛果芸香碱毛果芸香碱 toxicity1 Ciliary convulsion (spasm): drops

overdosage2 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