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

• Ephedrine
• Metaraminol
• Amphetamine
• Mephentermine

Direct-acting

• Phenylephrine
• Methoxamine

 

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

• Positive inotropic drug
• Vasopressor
• Relief of bronchospasm
• Treatment of allergic reactions
• Retardation of systemic absorption of local anaesthetics

 

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