Sympathomimetics
· Classification by action.
· Therapeutic uses.
· Adverse reactions.
· Uses of individual drugs.
Classification
1.
Sympathomimetics: drugs that partially or completely mimic the effects of
sympathetic nerve stimulation or adrenal medullary discharge.
2.
They may be classified into those that act:
a.
Directly, binding to the receptor: adrenaline, noradrenaline,
isoprenaline, dopamine, phenylephrine, dobutamine.
b.
Indirectly, by causing a release of noradrenaline from stores at nerve
endings: amphetamines, tyramine, ephedrine.
3.
Selectivity for adrenoceptors:
a.
Alpha + beta: adrenaline.
b.
Alpha1: noradrenaline.
c.
Alpha2: clonidine.
d.
Beta: isoprenaline.
e.
Beta1: dobutamine.
f.
Beta2: salbutamol, terbutaline, fenoterol.
4.
Pharmacokinetics:
a.
Short half-life of 2 min.
b
Metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase
(COMT).
c
These enzymes are present in large amounts in the liver and kidney.
d
MAO is also present in the intestinal mucosa.
Therapeutic uses
1.
Allergic reaction: acts as physiological antagonist to histamine.
2.
Chronic obstructive pulmonary disease: either of acute reversible attack
of asthma or chronic bronchitis or changes in emphysema.
3.
Hypotension due to reduction of sympathetic outflow or spinal
anaesthesia.
4.
Nasal congestion.
5.
Increase local infiltration and concentration of local anaesthetic.
6.
Topical hemostatic.
Adverse effects
1.
Anxiety.
2.
Tremulousness.
3.
Effects on heart:
a.
Tachycardia.
b.
Palpitations.
c.
Cardiac dysrhythmias: ventricular tachycardia and fibrillation.
4.
Tissue necrosis due to intense vasoconstriction around injection sites
occurs as a result of leakage from i.v. infusions.
5.
Contraindications:
a.
Angina.
b.
Hypertension.
c.
Hyperthyroidism.
Adrenaline:
1.
Adrenaline is used:
a.
as a vasoconstrictor with local anaesthetics to prolong their effects.
b.
as a topical mydriatic.
c.
for allergic reactions, s.c., i.m. or i.v.
2.
Route of administration:
a.
Must be chosen with care.
b.
Given s.c. there is intense vasoconstriction, which slows absorption and
so prolongs and smoothes effects.
c.
If there is circulatory collapse absorption will be too much delayed and
the i.m. route is preferred.
3.
Anaphylactic shock:
a.
Adrenaline is used i.m.
b.
May stabilize mast cells and reduce release of vasoactive autocoids.
4.
Glaucoma:
a.
Decreases intraocular pressure in chronic open-angle glaucoma.
b.
Contraindicated in close-angle glaucoma because they are mydriatics.
5.
Accidental overdose:
a.
Treated with propranolol to block the cardiac beta effects and
phentolamine or chlorpromazine to control the alpha effects.
b.
Beta-block alone is hazardous as the then unopposed alpha-receptor
vasoconstriction causes hypertension.
Uses of other sympathomimetics
1.
Isoprenaline:
a.
A non-selective beta-receptor agonist.
b.
Relaxes smooth muscle, including that of blood vessels, has negligible
metabolic or vasoconstrictor effects.
c.
Principal uses are in complete heart block and occasionally in
cardiogenic shock.
d.
It can be given by infusion, or as tablets: either to be dissolved under
the tongue or as a sustained-release preparation.
2.
Dopamine:
a.
Agonist for specific dopamine (D1) receptors in the CNS and the renal and
other vascular beds (dilator) – promotes vasodilation of renal, splanchnic,
coronary and cerebral arteries.
b.
Activates presynaptic autoreceptors (D2) which suppress release of
noradrenaline.
c.
An agonist at B1 receptors in the heart and activates B1 receptors in the
blood vessels at high doses (vasoconstrictor).
d.
Given by continuous i.v. infusion.
e.
Stable for 24h in sodium chloride or dextrose; it is inactivated by
alkaline solution.
f.
Subcutaneous leak causes vasoconstriction and necrosis and should be
treated by local injection of an alpha blocker, e.g. phentolamine 5 mg, diluted.
3.
Dobutamine:
a.
Acts on B1 receptors of the heart.
b.
Has greater inotropic than chronotropic effects.
c.
May be useful in shock and low output heart failure.