Review of Pharmacology - 9E (2015)

Review of Pharmacology
it is converted to nor-adrenaline by dopamine β hydroxylase. This enzyme is inhibited by
disulfiram. Action of NA is terminated mainly by reuptake in the vesicles (inhibited by cocaine
and TCA) and partly by the metabolism through MAO and COMT. Further conversion of NA
to adrenaline (A) is carried out in the adrenal medulla. This methylation step occurs in the
cytoplasm with the help of phenyl ethanolamine-N-methyl transferase. Sympathetic neurons
lack this enzyme; therefore catecholamine synthesis is stopped at NA level.
NA remains stored in the vesicles. Stimulation of this neuron by the action potential
increases the influx of Ca 2+ and results in exocytosis of NA in the synaptic cleft.
Exocytosis is inhibited by bretylium and guanethidine. NA released in the synapse acts on
post-synaptic receptors (to produce various effects) as well as presynaptic receptors (to
modulate its own release).
Autonomic Nervous System
66
Stimulation of b 2
receptors
initially causes efflux of K + from
liver (hyperkalemia) that is
followed by hypokalemia (due to
uptake by skeletal muscles).
ACTIONS OF SYMPATHETIC SYSTEM
• Heart: Positive chronotropic, ionotropic and dromotropic effects are seen due to
stimulation of β 1
receptors.
• Blood vessels: Stimulation of α 1
receptors causes vasoconstriction whereas β 2
stimulation leads to dilation of blood vessels. Effect of sympathetic system depends
on the predominant type of receptor (α 1
or β 2
) present in a particular vascular bed.
Skin, mucosal and splanchnic blood vessels are constricted due to predominance
of α 1
receptors whereas skeletal muscular blood vessels and coronaries are dilated
because of the presence of β 2
receptors in excess. Renal vessels contain both α 1
(vasoconstriction) and D 1
(vasodilator) receptors and sympathetic stimulation cause less
increase in vascular resistance here than in other vascular beds.
• GIT: Smooth muscles of GIT are relaxed by direct action of β 2
receptors and indirect
action of α 2
receptors. Latter are present presynaptically on the cholinergic neurons
(heteroceptors) and results in decreased release of ACh.
• Urinary system: Urinary retention can occur due to relaxation of detrussor by β 2
action
and contraction of trigone (sphincter) by α 1
action.
• Genital system: Pregnant uterus is relaxed by β 2
stimulation. Activation of α 1
receptors
in vas deferens, seminal vesicle and prostate facilitates ejaculation.
• Bronchus: Bronchial smooth muscle contains β 2
receptors but no sympathetic supply.
Exogenous drugs can cause bronchodilation by stimulation of β 2
receptors. Mucosal
vasoconstriction (by action on α 1
receptors) further increases the luminal diameter
of bronchus.
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