Catecholamine - Adrenaline

CATECHOLAMINES - ADRENALINE

Adrenaline: (Epinephrine)

  • It is an endogenous catecholamine and major hormone secreted by adrenal medulla. Commercial preparation is white to off white micro crystalline powder or granules which on exposure to light turns reddish (due to oxidation) with loss of activity.
  • Both endogenous and commercial adrenaline is in levo form which is 15 times more potent than dextro isomer.
  • Pharmacological effects
    • Adrenaline is a potent directly acting drug that interacts with all subtypes ( α 1, α 2 , β1, β2 and β3) of adrenergic receptors.

Cardiovascular system

  • Blood vessels
    • The main action of adrenaline is exerted on smaller arterioles and pre-capillary sphincter. Vasoconstriction predominates in cutaneous, mucous membrane, mesenteric and renal beds and occurs primarily through α1- receptors. There is marked reduction in blood flow to these structures when adrenaline is injected.
    • On the other hand, vasodilatation predominates in skeletal muscles, liver and coronary blood vessels. Vasodilatation is mediated by β2 receptor. Skeletal muscles blood vessels have both α and β2 receptors, but β2 are more sensitive to adrenaline than α receptors.
    • Large doses of adrenaline however causes vasoconstriction in skeletal muscles because α mediated action overrides β2 mediated relaxation.
  • Blood pressure
    • Effect of adrenaline on BP depends on dose, route and rate of administration.
    • Adrenaline given by slow IV infusion, SC injection or in slow doses (0.1µg/kg) causes fall in BP.
    • If a pharmacological dose of (1-3µg/kg) of adrenaline is given by rapid IV route, it produces a characteristic biphasic response on BP because the initial rise due to α1 activity followed by β2 activity.
    • The immediate raise in BP is mediated by myocardial stimulation and peripheral vasoconstriction.
  • Heart
    • Adrenaline is a powerful cardiac stimulant.
    • Both the heart rate and force of contraction are increased, resulting in a marked increase in cardiac output and cardiac oxygen consumption. These effects are mediated by β1 receptors.
  • Smooth muscles
    • Effects of adrenaline on smooth muscles of different organs and systems depend on the type of adrenergic receptors available in them.
    • Activation of α1 receptors produces contraction of all smooth muscles except GI tract, mainly from release of intracellular calcium through the action of second messenger IP3. Relaxation of smooth muscles is mediated by β2 receptors which increase intracellular cAMP concentration.
  • GI tract
    • In general adrenaline relaxes the smooth muscles of the GI tract, mediated by the activation of both the α and β receptors.
    • Frequency and amplitude of peristaltic movements is decreased. However, the sphincters are contracted. Gastric juice secretion is decreased and the saliva produced is thick and scanty.
  • Uterus
    • Response varies depending on the species and stage of gestation. In human adrenaline contracts gravid and non-gravid uterus when examined in vitro.
    • In situ, however, adrenaline relaxes the uterus in non-gravid stage, but contracts uterus during late pregnancy. Contraction of uterus is mediated through α receptors and  relaxation is mediated via β2 receptors.

    Species       Non-gravid uterus              Gravid uterus

Rat             Relaxation                               Relaxation

Rabbit       Contraction                              Contraction

Cat             Relaxation                               Contraction

Sheep        Contraction                             Relaxation

  • Urinary bladder
    • Relaxes detrusor muscle of bladder through receptors and contracts trigone and sphincter muscle via α receptor activation.
    • Net effect is retention of urine.
  • Respiratory tract
    • Adrenaline causes broncho dilatation by relaxing bronchial smooth muscles through activation of β2 receptors. However, only the contracted bronchioles are dilated and normal bronchioles are not affected.
    • Adrenaline also decreases bronchial secretions and produce decongestion via α receptors.
    • High doses of adrenaline cause pulmonary oedema by shifting blood from system pulmonary tree.
  • Eye
    • Adrenaline causes mydriasis due to contraction of radial muscle of the iris (α1 action).
    • However, this action is minimal when applied topically as adrenaline penetrates cornea very poorly.

Metabolic effects

  • Produces significant hyperglycaemic effect, which result from
    • increased glycogenolysis in liver (β2 action)
    • increased release of glucagon (β2 action)
    • decreased release of insulin (α2 action)
  • Increases concentration of free fatty acids in blood by stimulating β receptors in adipose tissues.
  • In general adrenaline causes conversion of energy sources of glycogen and fat to glucose and free fatty acids, which acts as readily available energy sources.
  • Other effects
    • Adrenaline contracts smooth muscles of spleen capsule (α effect), this discharges more blood into circulation.
    • Causes contraction of piloerector muscles, so hair become erect (α1 effect)
    • Adrenaline has little effect on the brain as it penetrates the blood brain barrier poorly.
  • Pharmacokinetics
    • Adrenaline is not effective orally as it is metabolised rapidly by MAO and COMT present in intestinal wall and liver. Absorption from IM injection site is rapid, but is relatively slower following SC injection. In emergency adrenaline can be given by IV.
    • In general adrenaline parenterally has rapid action, but a brief duration of action. Most of the absorbed adrenaline is metabolised by the hepatic COMT and MAO into an inactive metabolites an excreted in urine. Adrenaline does not cross blood brain barrier, but crosses the placenta an is distributed in milk.
    • Adrenaline can induce a feeling of fear or anxiety, tremors, excitability, vomiting, pallor and lactic acidosis.
    • Large doses may cause cerebral haemorrhage, cardiac arrhythmias, pulmonary oedema, dyspnoea, renal failure, metabolic acidosis and cold skin.
  • Contraindications
    • Adrenaline is contraindicated in narrow-angle glaucoma, general anaesthesia with halogenated hydrocarbons, coronary insufficiency, hypertension, hyperthyroidism and along with non-sedative β receptor blocking drugs.

Clinical uses

  • Drug of choice in anaphylaxis
  • Adrenaline restores cardiac rhythm in cardiac arrest (asystole)
  • Added with local anaesthetics (1:100,000)to decrease their absorption from the injection site.
  • Adrenaline relieves bronchospasm in acute asthma.
  • Adrenaline reduces intraocular pressure in open-angle glaucoma when applied topically as 2% solution. It reduces formation of aqueous humour by vasoconstriction of the ciliary blood vessels
Last modified: Monday, 18 June 2012, 6:25 AM