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Pharmacology: Pharmacokinetics: As a result of enzymatic degradation in the gut and first-pass metabolism in the liver, adrenaline is almost totally inactive when given orally. Systemic absorption can occur after topical application for example of eye drops. Adrenaline acts rapidly after intramuscular and subcutaneous injection; the latter route is, however, sometimes considered to be slower and therefore less reliable for emergency use. Although absorption is slowed by local vasoconstriction it can be hastened by massaging the injection site.
Most adrenaline that is either injected into the body or released into the circulation from the adrenal medulla is very rapidly inactivated by processes that include uptake into the adrenergic neurons, diffusion, and enzymatic degradation in the liver and body tissues. The half-life of circulating adrenaline is only about 1 minute. One of the enzymes responsible for the chemical inactivation of adrenaline is catechol-O-methyltransferase (COMT), the other is monoamine oxidase (MAO). In general, adrenaline is methylated to metanephrine by COMT followed by oxidative deamination by MAO and eventual conversion to 4-hydroxy-3-methoxymandelic acid (formerly termed vanillylmandelic acid; VMA), or oxidatively deaminated by MAO and converted to 3,4-dihydroxymandelic acid which, in turn, is methylated by COMT, once again to 4-hydroxy-3-methoxymandelic acid; the metabolites are excreted in the urine mainly as their glucuronide and ethereal sulfate conjugates.
The ability of COMT to effect introduction of a methyl group is an important step in the chemical inactivation of adrenaline and similar catecholamines (in particular, noradrenaline). It means that the termination of the pharmacological response of catecholamines is not simply dependent upon MAO. In its role of neurotransmitter intraneuronal catecholamine (mainly noradrenaline) is, however, enzymatically regulated by MAO.
Adrenaline crosses the placenta to enter fetal circulation.
