As their name suggests, these drugs resemble sympathetic nerve stimulation in their effects;
they may be divided into two groups on the basics of their chemical structure.
- Catecholamines: -these are compounds which have the catechol nucleus.
Catecholamines have a direct action on sympathetic effectors cells through interactions with
receptor sites on the cell membrane.
The group includes adrenaline, noradrenaline, dopamine, isoprenaline, and dobutamine.
- Noncatecholmines: – lack the catechol nucleus.
They may directly act on the receptors or may indirectly release the physiologic catecholaminese.g. ephedrine, phenylephrine, amphetamine
Adrenergic drugs, like cholinergic drugs, can be grouped by mode of action and by the spectrum
of receptors that they affect.
a. Direct mode of action: directly interact with and activate adrenoreceptors, e.g., adrenaline
and noradrenaline
b. Indirect mode of action: their actions are dependent on the release of endogenous
catecholamines. This may be
i. Displacement of stored catecholamies from the adrenergic nerve endings, e.g., - Inhibition of reuptake of catecholamines already released, e.g. cocaine, tricyclic
- antidepressants
- Both types of sympathomimetics, direct and indirect, ultimately cause activation of
- adrenoreceptors leading to some or all characteristic effects of the catecholamines.
Organ-system Effects of Activation of the Adrenergic System
- CVS:
a. Heart: increased rate and force of contraction, increased cardiac output, myocardial
demand, and AV conduction
b. Blood Vessels and Blood pressure: constriction of blood vessels in the skin and
mucous membranes
- Dilatation of skeletal muscle vessels
- Adrenaline increases systolic and decreases diastolic blood pressure at low doses
but increases both at higher doses - Noradrenaline increases both systolic and diastolic blood pressure
- Smooth Muscle:
a. Bronchi: relaxation.
b. Uterus: relaxation of the pregnant uterus
c. GIT: relaxation of wall muscles and contraction of sphincters
d. Bladder: relaxation of detrusor muscle; contraction of sphincter and trigone muscle - Eye: mydriasis; reduction of intraocular pressure in normal and glacucomatous eyes
- Respiration: Bronchodilatation; relief of congestion; mild stimulation of respiration
- Metabolic: Increased hepatic glycogenolysis; decreased peripheral glucose intake;
increased free fatty acids in the blood (lipolysis) - CNS: excitement, vomting, restlessness
- Skeletal muscle: facilitation of neuromuscular transmission and vasodilatation
Drugs Acting on the Adrenergic Receptor Subtypes
α1 α2 β1 β2
Agonist Phenylephrine
Methoxamine
Clonidine
Oxymetazoline
Dobutamine
Isoproterenol
Terbutaline
Salbutamol
Terbutaline
Isoetharine
Antagonist Prazosin
Phentolamine
Phenoxybenzamine
Yohimbine
Phentolamine
Phenoxybenzamine
Propranolol
Pindolol
Atenolol
Metoprolol
Timolol
Propranolol
Pindolol
Butoxamine
Timolol
Adrenaline stimulates all the four receptor subtypes.
Noradrenaline stimulates both alpha receptors and beta1 but has very poor affinity for beta2
receptors. Labetalol blocks all beta receptors as well as some alpha receptors.
ADRENALINE
This is the prototype of adrenergic drugs and is produced in the body by the cells of the Adrenal
medulla and by chromaffin tissues.
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Pharmacokinetics
Adrenaline is rapidly destroyed in the gastrointestinal tract, conjugated, and oxidized in the liver.
It is therefore ineffective when given orally and should be given intramuscularly or
subcutaneous. Intravenous injection is highly dangerous and is likely to precipitate ventricular
fibrillation. The drug may how ever, be given by nebulizer for inhalation when its relaxing effect
on the bronchi is desired or it may be applied topically to mucus membranes to produce
vasoconstriction. Because of the extensive metabolism of the drug in liver, little is excreted
unchanged in the urine.
Pharmacodynamics
Adrenaline directly stimulates all the adrenergic receptors both and brings about effects of
sympathetic nerve stimulation. Its action may be divided in to two, depending on the type of
receptor stimulated.
The α effects consist of vasoconstriction in skin and viscera, mydriasis, platelet aggregation and
some increase in blood glucose. The ß effects consists of increased contractility and rate of
heart with a decreased refractory period (ß1), vasodilatation in muscles and coronary vessels
(ß2), bronchial relaxation (ß2) uterine relaxation (ß2), hyperglycemia, lactic acidemia and
increased circulating free fatty acids.
Indications
- Acute bronchial asthma
- Anaphylaxis
- Local haemostatic to stop bleeding in epistaxis
- With local anesthesia to prolong the action
- Cardiac arrest
Adverse reactions - Anxiety, restlessness, headache tremor
- Anginal pain
- Cardiac arrhythmias and palpitations
- Sharp rise in blood pressure
- Sever vasoconstriction resulting in gangrene of extremities
- Tearing, conjunctival hyperemia
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Contra indications - Coronary diseases
- Hyperthyroidism
- Hypertension
- Digitalis therapy
- Injection around end arteries
NOR ADRENALINE
Nor adrenaline is the neurochemical mediator released by nerve impulses and various drugs
from the postganglionic adrenergic nerves. It also constitutes 20% of the adrenal medulla
catecholamine out put.
Pharmacokinetics
Like adrenaline, noradrenaline is ineffective orally so it has to be given intravenously with
caution. It is not given subcutaneous or intramuscularly because of its strong vasoconstrictor
effect producing necrosis and sloughing. The metabolism is similar to adrenaline; only a little is
excreted unchanged in urine.
Pharmacodynamics
Nor adrenaline is a predominantly α receptor agonist with relatively less β agonist action when
compared to adrenaline.
Indication
Nor adrenalines is used as hypertensive agent in hypotensive states
E.g. During spinal anesthesia or after sympathectomy.
Adverse effects include:
- Anxiety, headache, bradycardia are common side effects
- Severe Hypertension in sensitive individuals
- Extravasation of the drug causes necrosis and sloughing.
ISOPRENALINE DOPAMINE, DOBUTAMINE. These are the other catecholamines which have
similar properties to adrenaline and noradrenaline.
Dopamine is naturally occurring and is a precursor of noradrenaline. The other two-isoprenaline
and dobutamine- are synthetic. These drugs have advantage over the others because they are
more selective in their action so that they have fewer side effects than adrenaline and nor
adrenaline. Dopamine and dobutamine are very useful drugs for the treatment of shock.
NON- CATECHOLAMINES
Most of the non- catecholamines function by releasing the physiologic catecholamines from the
postganglionic nerve endings
EPHEDRINE
Pharmacokinetics
Ephedrine in absorbed from the gastrointestinal tract and from all parenteral sites. It has a good
distribution through out the body and is resistant to hydrolysis by the liver enzymes. Major
proportion of the drug is excreted unchanged in the urine. Because of its stability to metabolism
it has long duration of action than the catecholamines.
Pharmacodynamics
Ephedrine stimulates both α and β receptors. This effect is partly by a direct action on the
receptors and partly indirectly by releasing noradrenaline from its tissue stores the effect of the
drug to various organs and systems is similar to that of adrenaline. It is also a mild CNS
stimulant.
Indications:
- Bronchial asthma: – usually as a prophylactic for prevention of attacks
- Nasal decongestion
- Mydriasis
- Heart block
- Nocturnal enuresis
Side effects
The side effects are similar to those of adrenaline; but in addition it may produce insomnia and
retention of urine.
Contraindications
They are the same as Adrenaline.
Based on their selectivity to specific receptors the rest of the catecholamines, are classified but
it is very difficult to exhaust all the drugs. More over their effect and pharmacology is discussed
where they are clinically indicated.
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