Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: ALK-Abelló A/S, Bøge Allé 6-8, DK-2970 Hørsholm
Pharmacotherapeutic group: Cardiac stimulants excl. cardiac glycosides, adrenergic and dopaminergic agents.
ATC code: C01CA24
Adrenaline is a catecholamine which stimulates the sympathetic nervous system (both alpha and beta receptors) by which cardiac rate, cardiac output and coronary circulation is raised. Adrenaline through its action on beta receptors on bronchial smooth muscles causes bronchial smooth muscle relaxation which alleviates wheezing and dyspnoea.
Adrenaline is a naturally occurring substance produced by the adrenal medulla and secreted in response to exertion or stress. It is rapidly inactivated in the body mostly by the enzymes COMT and MAO. The liver is rich in these enzymes and is an important, although not essential, tissue in the degradation process. Much of the dose of adrenaline is accounted for by excretion of metabolites in the urine.
The plasma half-life of adrenaline is about 2.5 min. However local vasoconstriction may retard absorption, so that the effects can last longer than the half-life would predict. Massage around the injection area is advised to accelerate absorption.
In an exploratory PK/PD study the mean plasma concentration-time curves were biphasic with a first peak within approx. 8-10 min followed by a slower increase until a second peak (plateau) was reached after approx. 30-40 min following injection of Jext. There was however a large variability in shape of the individual plasma concentration-time profiles. The results suggest that the adrenaline absorption in patients with a thick sub-cutaneous fat layer (i.e. STMD, skin to muscle depth >20mm) is slower than in subjects with a thinner sub-cutaneous fat layer.
Whereas plasma exposure was apparently comparable between Jext and IM injection in the first 16 minutes for the overall population, when data were evaluated by STMD cohort, the plasma exposure up to 30 minutes was generally lower in Jext compared to manual IM injection in the STMD >20 mm cohort. The point estimates of the Jext to manual IM injection ratio were 0.39 (90% CI 0.20-0.75) for AUC0-8mins, 0.56 (90% CI 0.31-0.99) for AUC0-16mins and 0.66 (90% CI 0.39-1.12) for AUC0-30mins suggesting consistently lower exposure in the first 30 minutes following administration with Jext compared to manual IM injection in the STMD >20 mm cohort.
Adrenaline has been utilised in the treatment of allergic emergencies for many years. There is no preclinical data of relevance available.
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