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Section IIICardiovascular drugsMechanism of action
Adrenaline exerts its effects viaα-andβ-adrenoceptors.α 1 -Adrenoceptor activation
stimulates phospholipase C (via Gq), which hydrolyzes phosphatidylinositol bispho-
sphate (PIP 2 ). Inositol triphosphate (IP 3 )isreleased, which leads to increased Ca^2 +
availability within the cell.α 2 -Adrenoceptor activation is coupled to Gi-proteins that
inhibit adenylate cyclase and reduce cAMP concentration.β-Adrenoceptors are cou-
pled to Gs-proteins that activate adenylate cyclase, leading to an increase in cAMP
and specific phosphorylation depending on the site of the adrenoceptor.Effects
Cardiovascular – the effects of adrenaline vary according to dose. When adminis-
tered as a low-dose infusion,βeffects predominate. This produces an increase in
cardiac output, myocardial oxygen consumption, coronary artery dilatation and
reduces the threshold for arrhythmias. Peripheralβeffects may result in a fall in
diastolic blood pressure and peripheral vascular resistance. At high doses by infu-
sion or when given asa1mgbolus during cardiac arrest,α 1 effects predominate
causing a rise in systemic vascular resistance. It is often used in combination with
local anaesthetics to produce vasoconstriction before dissection during surgery.
When used with halothane, the dose should be restricted to 100μgper 10 min-
utes to avoid arrhythmias. It should not be infiltrated into areas supplied by end
arteries lest their vascular supply become compromised. Extravasation can cause
tissue necrosis.
Respiratory – adrenaline produces a small increase in minute volume. It has
potent bronchodilator effects although secretions may become more tenacious.
Pulmonary vascular resistance is increased.
Metabolic – adrenaline increases the basal metabolic rate. It raises plasma glucose
bystimulating glycogenolysis (in liver and skeletal muscle), lipolysis and gluconeo-
genesis. Initially insulin secretion is increased (aβ 2 effect) but is often overridden
by anαeffect, which inhibits its release and compounds the increased glucose
production. Glucagon secretion and plasma lactate are also raised. Lipase activity
is augmented resulting in increased free fatty acids, which leads to increased fatty
acid oxidation in the liver and ketogenesis. These metabolic effects limit its use,
especially in those with diabetes. Na+re-absorption is increased by direct stimula-
tion of tubular Na+transport and by stimulating renin and, therefore, aldosterone
production.β 2 -Receptors are responsible for the increased transport of K+into
cells, which follows an initial temporary rise as K+is released from the liver.
Central nervous system – it increases MAC and increases the peripheral pain
threshold.
Renal – renal blood flow is moderately decreased and the increase in bladder
sphincter tone may result in difficulty in micturition.