Uterus (p2): relaxation (pregnant) Skeletal muscle: tremor (¡};)
Metabolic effects: hypokalemia (Pj) hepatic glycoge no lysis (p2) lipolysis (p,,p2)
Bladder detrusor: relaxation
Intestinal smooth muscle relaxation is mediated by u- ant (^-adrenoceptor effects:1 a,-receptors on the nerve endin noradrenaline release.
g i.e. presynaptic autoreceptors mediate negative feedback which inhibits
1 For the role of subtypes (a, and ot2) see prazosin.
2 Effects on intraocular pressure Involve both a- and (3-adrenoceptors as well as cholinoceptors.
3 Cardiac Preceptors mediate effects of sympathetic nerve stimulation. Cardiac P2-receptors mediate effects of circulating adrenaline, when this is secreted at a sufficient rate, e.g. following a myocardial infarction or in heart failure. Both receptors are coupled to the same intracellular signalling pathway (cyclic AMP production) and mediate the same biological effects.
The use of the term cardioselective to mean P,-receptor selective only, especially in the case of P-receptor blocking drugs, is no longer appropriate. Although in most species the [^-receptor is the only cardiac P-receptor, this is not the case in humans.What is not generally appreciated is that the endogenous sympathetic neurotransmitter, noradrenaline, has about a 20-fold selectivity for the p-receptor — similar to that of the antagonist, atenolol — with the consequence that under most circumstances, in most tissues, there is little or no P2-receptor stimulation to be affected by a nonselective p-blocker.Why asthmatics should be so sensitive to p-blockade is paradoxical: all the bronchial P-receptors are P2, and the bronchi themselves are not innervated by adrenergic fibres; the circulating adrenaline levels are, if anything, low in asthma.
• indirectly, by discharging noradrenaline stored in nerve endings2 (amfetamine)
• by preventing reuptake into the adrenergic nerve ending of released noradrenaline (and dopamine) (cocaine, tricyclic antidepressants and noradrenaline-selective reuptake inhibitors such as roboxetine)
2 Fatal hypertension can occur when this class of agent is taken by a patient treated with monoamine oxidase inhibitor.
• by preventing the destruction of noradrenaline (and dopamine) in the nerve ending (monoamine oxidase inhibitors)
• by depleting the stores of noradrenaline in nerve endings (reserpine)
• by preventing the release of noradrenaline from nerve endings in response to a nerve impulse (guanethidine)
• by activation of adrenoceptors on adrenergic nerve endings that inhibit release of noradrenaline (a2-autoreceptors) (clonidine) • by blocking sympathetic autonomic ganglia (trimetaphan).
All the above mechanisms operate in both the central and peripheral nervous systems. This discussion is chiefly concerned with agents that influence peripheral adrenergic mechanisms.
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