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Chapter: Basic & Clinical Pharmacology : Adrenoceptor Agonists & Sympathomimetic Drugs

Endogenous Catecholamines

Epinephrine (adrenaline) is an agonist at bothαandβreceptors.It is therefore a very potent vasoconstrictor and cardiac stimulant.

SPECIFIC SYMPATHOMIMETIC DRUGS

Endogenous Catecholamines

Epinephrine (adrenaline) is an agonist at bothαandβreceptors.It is therefore a very potent vasoconstrictor and cardiac stimulant. The rise in systolic blood pressure that occurs after epinephrine release or administration is caused by its positive inotropic and chronotropic actions on the heart (predominantly β1 receptors) and the vasoconstriction induced in many vascular beds (α recep-tors). Epinephrine also activates β2 receptors in some vessels (eg, skeletal muscle blood vessels), leading to their dilation. Consequently, total peripheral resistance may actually fall, explaining the fall in diastolic pressure that is sometimes seen with epineph-rine injection (Figure 9–6; Table 9–4). Activation of β2 receptors in skeletal muscle contributes to increased blood flow during exer-cise. Under physiologic conditions, epinephrine functions largely as a hormone; after release from the adrenal medulla into the blood, it acts on distant cells.



Norepinephrine (levarterenol, noradrenaline) is an agonist atboth α1 and α2 receptors. Norepinephrine also activates β1 recep-tors with similar potency as epinephrine, but has relatively little effect on β2 receptors. Consequently, norepinephrine increases peripheral resistance and both diastolic and systolic blood pressure. Compensatory baroreflex activation tends to overcome the direct positive chronotropic effects of norepinephrine; however, the posi-tive inotropic effects on the heart are maintained.

Dopamine is the immediate precursor in the synthesis of nor-epinephrine (see Figure 6–5). Its cardiovascular effects were described above. Endogenous dopamine may have more impor-tant effects in regulating sodium excretion and renal function. It is an important neurotransmitter in the central nervous system and is involved in the reward stimulus relevant to addiction. Its deficiency in the basal ganglia leads to Parkinson’s disease, which is treated with its precursor levodopa. Dopamine receptors are also targets for antipsychotic drugs.



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