Adrenergic Agonists/Sympathomimetic drugs

Adrenergic Agonists/Sympathomimetic drugs

Activate adrenergic receptors  produces a response similar to the sympathetic nervous system

4 mechanisms of activation of adrenergic receptors:
1) Binds to receptor  direct action as it mimics the natural neurotransmitter
2) Promote release of neurotransmitter from terminal of sympathetic nerves
3) Inhibits reuptake of the neurotransmitter
4) Inhibits inactivation/breakdown of the neurotransmitter

Two chemical types of adrenergic agonists:
1) Catecholamines:
• contain a catechol and an amine group
• have short half lives and can not be taken orally (quickly destroyed by enzymes located in liver and intestinal wall – monoamine oxidase (MAO) and catechol-o-methyltransferase)
• can not cross blood-brain barrier (polar molecules)
• eg epinephrine, dopamine, dobutamine, isoproternol

2) Noncatecholamines:
• do not contain the catechol part
• not broken down by catechol-o-methyltransferase (COMT) and slowly metabolised by monoamine oxidase  much longer half lives and can be taken orally
• less polar  can cross blood brain barrier

Effects of activation of adrenergic receptors:
a) Alpha1-adrenergic receptors:
• vasoconstriction, mydriasis (dilation of pupil)
• used for haemostasis; nasal decongestion; delay local anaesthetic absorption; elevate blood pressure
• adverse effects – hypertension, bradycardia
• activated by epinephrine, ephedrine, norepinephrine, phenylephrine, dopamine

b) Alpha2-adrenergic receptors:
• inhibits release of norepinephrine in receptors located in the periphery
• in CNS – stimulation of alpha2 receptors  reduction of sympathetic outflow to heart in blood vessels
• activated by epinephrine, ephedrine, norepinephrine,

c) Beta1-adrenergic receptors:
• used for cardiac arrest (activation of receptors  initiates contraction if heart has stopped beating); heart failure (activation increases force of contraction); shock; AV heart block
• activated by epinephrine, ephedrine, norepinephrine, isoproterenol, dobutamine, dopamine

d) Beta2-adrenergic receptors:
• clinically relevant receptors are located in lungs and uterus
• used for asthma – activation of receptors promote vasodilation
• activated by epinephrine, ephedrine, isoproterenol, terbutaline