Catecholamine Adrenaline Pharmacology

Catecholamines

• Adrenaline (Epinephrine) is a natural sympathomimetic catecholamine present in the suprarenal medulla (80%) and CNS.
• It darkens due to its oxidation to adrenochrome, which is toxic.

Source and Chemistry

• Adrenaline is a sympathomimetic amine derived from the amino acid tyrosine.

Pharmacokinetics

• Adrenaline is ineffective when administered orally, as it is metabolized by COMT in the GIT and liver.
• Inhalation, intramuscular, local, intraosseous, and endotracheal routes are effective.
• The termination of action also occurs by uptake into nerve terminals.
• Excretion occurs through the kidneys (5% in urine) and small parts remain unchanged.

Pharmacodynamics

• Adrenaline has local actions, mainly alpha-1, including:
  • Vasoconstriction (VC) of cutaneous blood vessels, mucous membrane blood vessels of the nose, and conjunctival blood vessels.
  • VC of mucous membrane of bronchi and bronchodilatation.

Heart

• Adrenaline acts on the heart, increasing contraction force (inotropic), heart rate (chronotropic), and conduction (dromotropic).
• It also increases excitability, leading to arrhythmia.

Blood Vessels

• Adrenaline causes vasoconstriction of skin and mucous membrane blood vessels (alpha).
• It increases cardiac output and systolic blood pressure, with varying diastolic pressure.

Smooth Muscle Effects

• Adrenaline acts on:
  • Eye: vasoconstriction (alpha), active mydriasis (alpha), and decreased IOP (in open-angle glaucoma).
  • Respiration: bronchodilatation (beta-2) and vasoconstriction (alpha).
  • GIT: relaxation of wall (alpha + beta-1, beta-2) and contraction of sphincters (alpha).
  • Urinary: relaxation of wall (beta-2) and constriction of trigone and sphincters (alpha).
  • Sex organs: ejaculation (male) and relaxation of uterus (female, pregnant).

Metabolic Effects

• Adrenaline increases:
  • Blood glucose levels through liver glycogenolysis (beta-2) and insulin secretion (alpha).
  • Blood lactate through glycogenolysis in muscles.
  • Free fatty acid (FFA) through lipolysis (beta-1, beta-3).
  • Calorigenic action by 20% increase in O2 consumption.
• Initial increase in K+ release from the liver, followed by sustained decrease in K+ due to uptake by muscles (beta-2).

Antiallergic Effects

• Adrenaline suppresses allergy by counteracting histamine (bronchospasm, vasoconstriction).
• It is the physiological releaser of P cells.

Local Uses

• Hemostatic in epistaxis as a nasal pack.
• Decongestant of mucous membranes of the nose and eye.
• Used as eye drops in open-angle glaucoma to lower IOP.
• Induction and maintenance of mydriasis during intra-ocular surgery.
• Inhalation in acute bronchial asthma.

Systemic Uses

• Anti-allergic drug of choice in anaphylactic shock.
• Used in cardiac resuscitation.