1. Pharmacology
        1.3. Autonomic drugs
1.3.1. Sympathomimetics

Sympathomimetics

[Ref: SH(H)2 chp 12]

Group characteristics

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

Classification

Natural catecholamines

Epinepherine

Norepinepherine

Dopamine

Synthetic catecholamines

Isopropterenol

Dobutamine

Synthetic non-catecholamines

Indirect-acting

Triggers release of endogenous NE from postganglionic sympathetic nerve endings

Direct-acting

 

NB:

Noncatecholamines which lack substitents on the benzene ring has higher lipid solubility
--> Prominent CNS stimulation

Catecholamines have limited lipid solubility
--> CNS stimulation unlikely

Mechanism of action

Activation (direct or indirect) of alpha-adrenergic, beta-adrenergic, or dopaminergic receptors
* All G-protein coupled receptors

Actions

Vasoconstriction (especially renal and cutaneous)

Vasodilation (skeletal muscles)

Bronchodilations

Cardiac stimulation (HR, contractility, propensity for arrhythmias)

Glycogenolysis

Liberation of free fatty acid

 

Clinical use

 

Metabolism

Catecholamines

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

Synthetic noncatecholamines

Not affected by COMT

Metabolism is dependent on MAO
--> Slower

Route of administration

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

 

Epinephrine

CVS Effects

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)

Airway

Relaxation of bronchial smooth muscles (via beta2)

Metabolic effect

 

 

 

 



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