Pharmacology for Anaesthesia and Intensive Care

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12 Sympathomimetics

Kinetics

Adrenaline is not given orally due to inactivation. Subcutaneous absorption is less

rapid than intramuscular. Tracheal absorption is erratic but may be used in emer-

gencies where intravenous access is not available.

It is metabolized by mitochondrial MAO and catechol O-methyl trans-

ferase (COMT) within the liver, kidney and blood to the inactive 3-methoxy-4-

hydroxymandelic acid (vanillylmandelic acid or VMA) and metadrenaline, which

is conjugated with glucuronic acid or sulphates, both of which are excreted in the

urine. It has a short half-life (about 2 minutes) due to rapid metabolism.

Noradrenaline

Presentation and uses

Noradrenaline is presented as a clear solution containing 0.2–2 mg.ml−^1 nora-

drenaline acid tartrate, which is equivalent to 0.1–1 mg.ml−^1 respectively of nora-

drenaline base, and contains the preservative sodium metabisulphite. It is used as an

intravenous infusion (dose range 0.05–0.5μg.kg−^1 .min−^1 )toincrease the systemic

vascular resistance.

Mechanism of action

Itsactions are mediated mainly via stimulation ofα 1 -adrenoceptors but also

β-adrenoceptors.

Effects


Cardiovascular – the effects of systemically infused noradrenaline are slightly

different from those of endogenous noradrenaline. Systemically infused nora-

drenaline causes peripheral vasoconstriction, increases systolic and diastolic

blood pressure and may cause a reflex bradycardia. Cardiac output may fall and

myocardial oxygen consumption is increased. A vasodilated coronary circulation

carries an increased coronary blood flow. Pulmonary vascular resistance may be

increased and venous return is increased by venoconstriction. In excess it produces

hypertension, bradycardia, headache and excessive peripheral vasoconstriction,

occasionally leading to ischaemia and gangrene of extremities. Extravazation can

cause tissue necrosis. Endogenously released noradrenaline causes tachycardia

and a rise in cardiac output.


Splanchnic – renal and hepatic blood flow falls due to vasoconstriction.


Uterus – blood flow to the pregnant uterus is reduced and may result in foetal

bradycardia. It may also exert a contractile effect and cause foetal asphyxia.


Interactions – despite being a direct-acting sympathomimetic amine it should be

used with caution in patients taking monoamine oxidase inhibitors (MAOI) as its

effects may be exaggerated and prolonged.