Tài liệu CLINICAL PHARMACOLOGY 2003 (PART 24) pdf

22

Adrenergic mechanisms and drugs

SYNOPSIS

Anyone who administers drugs acting on

cardiovascular adrenergic mechanisms requires

an understanding of how they act in order to

use them to the best advantage and with safety.

Adrenergic mechanisms

Classification of sympathomimetics: by mode

of action and selectivity for adrenoceptors

Individual sympathomimetics

Mucosal decongestants

Shock

Chronic orthostatic hypotension

Adrenergic mechanisms

The discovery in 1895 of the hypertensive effect of

adrenaline (epinephrine) was initiated by Dr Oliver,

a physician in practice, who conducted a series of

experiments on his young son into whom he injected

an extract of bovine suprarenal. The effect was

confirmed in animals and led eventually to the iso￾lation and synthesis of adrenaline in the early 1900s.

Many related compounds were examined and, in

1910, Barger and Dale invented the word sympatho￾mimetic1

and also pointed out that noradrenaline

(norepinephrine) mimicked the action of the

sympathetic nervous system more closely than did

adrenaline.

Adrenaline, noradrenaline and dopamine are

formed in the body and are used in therapeutics.

The natural synthetic path is:

tyrosine —> dopa —> dopamine —> noradrenaline —>

adrenaline.

Classification of

sympathomimetics

BY MODE OF ACTION

Noradrenaline is synthesised and stored in adrenergic

nerve terminals and can be released from these stores

by stimulating the nerve or by drugs (ephedrine,

amfetamine). These noradrenaline stores may be

replenished by i.v. infusion of noradrenaline, and

abolished by reserpine or by cutting the sympathetic

neuron.

Sympathomimetics may be classified as those

that act:

1. directly: adrenoceptor agonists, e.g. adrenaline,

1

'Compounds which ... simulate the effects of sympathetic

nerves not only with varying intensity but with varying

precision ... a term ... seems needed to indicate the types of

action common to these bases. We propose to call it

"sympathomimetic". A term which indicates the relation of

the action to innervation by the sympathetic system, without

involving any theoretical preconception as to the meaning of

that relation or the precise mechanism of the action/ Barger

G, Dale H H 1910 Journal of Physiology XLI: 19-50.

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