Bài giảng Thuốc tác dụng trên hệ cholinergic

THUỐC TÁC DỤNG TRÊN

HỆ CHOLINERGIC

Nguyễn Thùy Dương

Thuốc tác dụng trên hệ cholinergic

1. Phân tích được tác dụng, chỉ định, tác dụng không mong

muốn và thận trọng/chống chỉ đinh của các thuốc nhóm:

-Chủ vận M và N, chủ vận muscarinic, phong bế cholinesterase;

-Ức chế muscarinic, giãn cơ vân

2. So sánh được về cơ chế, tác dụng, chỉ định, tác dụng

không mong muốn giữa:

-Các thuốc kích thích hệ cholinergic (thuốc chủ vận M và N với chủ

vận M, phong bế cholinesterase);

-Mềm cơ cura loại chống khử cực với cura loại khử cực lâu bền

Mục %êu học tập

THUỐC TÁC DỤNG TRÊN HỆ CHOLINERGIC

•THUỐC KÍCH THÍCH HỆ CHOLINERGIC

•THUỐC ỨC CHẾ HỆ CHOLINERGIC

Lippincott's Illustrated Reviews: Pharmacology 6th Edn

THUỐC KÍCH THÍCH CHOLINERGIC

98 SECTION II Autonomic Drugs

nerves as well as on some tissues that are not innervated by these

nerves, eg, endothelial cells ( Table 7–1 ), and on those tissues

innervated by postganglionic sympathetic cholinergic nerves.

N i c o t i n i c r e c e p t o r s a r e p a r t o f a t r a n s m e m b r a n e p o l y p e p t i d e

whose subunits form cation-selective ion channels (see Figure 2–9 ).

These receptors are located on plasma membranes of postgangli-

onic cells in all autonomic ganglia, of muscles innervated by

somatic motor fibers, and of some central nervous system neurons

(see Figure 6–1 ).

Nonselective cholinoceptor stimulants in sufficient dosage can

produce very diffuse and marked alterations in organ system function

because acetylcholine has multiple sites of action where it initiates

both excitatory and inhibitory effects. Fortunately, drugs are available

that have a degree of selectivity, so that desired effects can often be

achieved while avoiding or minimizing adverse effects.

Selectivity of action is based on several factors. Some drugs

stimulate either muscarinic receptors or nicotinic receptors selec-

tively. Some agents stimulate nicotinic receptors at neuromuscular

junctions preferentially and have less effect on nicotinic receptors

in ganglia. Organ selectivity can also be achieved by using appro-

priate routes of administration (“pharmacokinetic selectivity”).

For example, muscarinic stimulants can be administered topically

to the surface of the eye to modify ocular function while minimiz-

ing systemic effects.

Cholinoceptor stimulants

Nerve

Heart and

smooth muscle

Glands and

endothelium

Alkaloids

Choline esters

Direct-acting

drugs

Neuromuscular

end plate,

skeletal muscle

Nicotinic

Receptors

Muscarinic

ACh Indirect-acting

drugs

Autonomic

ganglion

cells

Reversible

Irreversible

FIGURE 7–1 The major groups of cholinoceptor-activating drugs, receptors, and target tissues. ACh, acetylcholine.

TABLE 7–1 Subtypes and characteristics of cholinoceptors.

Receptor Type Other Names Location Structural Features Postreceptor Mechanism

M1Nerves Seven transmembrane segments,

Gq/11 protein-linked

IP3, DAG cascade

M2Cardiac M2Heart, nerves, smooth

muscle

Seven transmembrane segments,

Gi/o protein-linked

Inhibition of cAMP pro-

duction, activation of

K+ channels

M3Glands, smooth muscle,

endothelium

Seven transmembrane segments,

Gq/11 protein-linked

IP3, DAG cascade

M4CNS Seven transmembrane segments, Gi/o

protein-linked

Inhibition of cAMP

production

M5CNS Seven transmembrane segments,

Gq/11 protein-linked

IP3, DAG cascade

NMMuscle type, end plate

receptor

Skeletal muscle neuromus-

cular junction

Pentamer1 [(α1)2β1δγ)] Na+, K+ depolarizing ion

channel

NNNeuronal type, ganglion

receptor

CNS, postganglionic cell

body, dendrites

Pentamer1 with α and β subunits

only, eg, (α4)2(β2)3 (CNS) or

α3α5(β2)3 (ganglia)

Na+, K+ depolarizing ion

channel

1Pentameric structure in Torpedo electric organ and fetal mammalian muscle has two α1 subunits and one each of β1, δ, and γ subunits. The stoichiometry is indicated by sub-

scripts, eg, [(α1) 2 β1 δ γ]. In adult muscle, the γ subunit is replaced by an ε subunit. There are twelve neuronal nicotinic receptors with nine α (α2-α10) subunits and three (β2-β4)