[Ref: SH(H)2 chp 12]
All derived from beta-phenylethylamine
Presence of hydroxyl group on carbon 3 and 4 of the benzene ring
--> "Catechol"
--> Vital for activity at alpha and beta-adrenergic receptors
Epinepherine
Norepinepherine
Dopamine
Isopropterenol
Dobutamine
Triggers release of endogenous NE from postganglionic sympathetic nerve endings
NB:
Noncatecholamines which lack substitents on the benzene ring has higher lipid solubility
--> Prominent CNS stimulation
Catecholamines have limited lipid solubility
--> CNS stimulation unlikely
Activation (direct or indirect) of alpha-adrenergic, beta-adrenergic, or dopaminergic receptors
* All G-protein coupled receptors
Vasoconstriction (especially renal and cutaneous)
Vasodilation (skeletal muscles)
Bronchodilations
Cardiac stimulation (HR, contractility, propensity for arrhythmias)
Liberation of free fatty acid
All drugs containing 3,4-dihydroxybenzene (i.e. all catechol)
--> Rapidly inactivated by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)
Metabolites appear in urine as
* 3-methoxy-4-hydroxy mandelic acid (aka vanillylmandelic acid (VMA)
* Metanephrine
* Normetanephrine
(???)Role of pulmonary clearance
Not affected by COMT
Metabolism is dependent on MAO
--> Slower
Oral route is NOT effective due to metabolism in GIT mucosa and liver
E is administered S/C or IV
NE, Dopamine, and dobutamine are administered IV
Small doses (1 to 2 microgram/kg/min IV)
--> Mainly stimulation of beta2-receptor in the peripheral vasculature
Larger dose (4 microgram/kg/min IV)
--> Stimulation of beta1-receptor as well
Even larger dose (10 to 20 microgram/kg/min IV)
--> Both alpha and beta stimulation
* Alpha-receptor stimulation in most vascular beds (including renal and cutaneous)
Relaxation of bronchial smooth muscles (via beta2)