Pharmacology of Adrenaline and Beta-Blockers

Adrenaline

• Adrenaline is a sympathomimetic catecholamine
• It is present in the adrenal medulla (80% of secretions) and some CNS tracts
• Not absorbed orally

Adrenaline Kinetics

• Routes of administration: subcutaneous (1/2 mL of 1/1000 solution), inhalation (1/100 solution by nebulizer or atomizer), eye drops (2% solution), intra-cardiac (in cardiac resuscitation)
• Subcutaneous administration causes vasoconstriction, which slows absorption
• Inhalation is used in bronchial asthma
• Eye drops are used in open-angle glaucoma
• Intra-cardiac use is for impaired circulation during cardiac resuscitation

Adrenaline Fate

• Distribution: does not pass the blood-brain barrier
• Reuptake: by nerve endings and tissues (80%)
• Metabolism: by MAO (Monoamine oxidase) and COMT (Catechol-O-methyltransferase) (18%)
• Excretion: unchanged in urine (2%)

Adrenaline Actions

• Systemic actions:
  • Heart: increases heart rate and force of contraction
  • Blood vessels: constriction of skin, mucous membranes, and renal blood vessels, dilation of skeletal and coronary blood vessels.
  • Blood pressure: increase in systolic blood pressure (SBP) due to increased cardiac output (COP) and increased venous return, decrease in diastolic blood pressure (DBP) due to vasodilation of skeletal vessels and reduced peripheral resistance.
  • Respiratory: decongestion of bronchial mucosa, bronchodilation
  • Gastrointestinal Tract: constriction of sphincters and relaxation of intestinal wall.
  • Urinary Bladder: constriction of bladder sphincter, relaxation of bladder wall causing urine retention.
  • Uterus: contraction in early pregnancy, relaxation in late pregnancy
  • Skeletal Muscles: vasodilation, facilitation of neuromuscular transmission, anti-fatigue
  • Metabolic: hyperglycemia
  • Other: anxiety; physiological antagonist of histamine
• Local actions
  • Skin: localized vasoconstriction via alpha-1 receptors
  • Mucous membranes: (e.g., nasal): vasoconstriction via alpha-1 receptors - decongestion and homeostasis

Adrenaline Local Uses

• Open-angle glaucoma
• Haemostatic nasal pack in epistaxis (not in hypertension patients)
• With local anaesthetics (except cocaine): slows absorption, increases duration, reduces systemic toxicity and bleeding

Adrenaline Systemic Uses

• Anaphylactic shock and urticaria
• Acute bronchial asthma
• Acute insulin hypoglycemia
• Cardiac resuscitation
• Contracting ring of uterus during labor

Adrenaline Contraindications

• Around-the-finger and toe gangrene
• Hypertension
• Hemorrhagic shock
• Thyrotoxicosis
• Pulmonary embolism
• Digitalis administration, general anaesthesia causing cardiac arrhythmias
• Non selective beta blocker

Beta-Adrenergic Blockers

• Mechanism: competitive blocking of beta-adrenergic receptors
• Intrinsic Sympathetic Activity (ISA): partial agonist activity
• Classification:
  • Non-selective: blocks β1 and β2 receptors, e.g., propranolol, sotalol, timolol, pindolol; Additional a-blocking effect (e.g., labetalol and carvedilol)
  • Selective: blocks primarily β1 receptors, e.g., metoprolol, atenolol, bisoprolol, esmolol

Beta-Blockers Kinetics

• Absorption: orally and parenterally
• Distribution: throughout the body; highly lipophilic drugs like propranolol and timolol cross the BBB.
• Propranolol: extensive hepatic metabolism; short duration of action, given t.d.s (three times a day)
• Esmolol: rapid metabolism by RBC esterase; given by IV infusion; suitable for patients with renal or hepatic diseases

Beta-Blockers Pharmacodynamics

• Heart: decreases heart rate and force of contraction (by beta1)
• Blood vessels: vasodilation of skeletal muscles and coronary blood vessels (by beta2), vasoconstriction of skin, mucous membranes, and renal blood vessels (by alpha1)
• Anti-hypertensive: by decreasing sympathetic outflow and reducing renin secretion
• IOP: reduced formation of aqueous humor
• Bronchi: bronchospasm (by beta2 blockade)
• Metabolism: hypoglycemic effect, masks symptoms of hypoglycemia

Beta-Blockers Uses

• Heart: arrhythmias, angina, myocardial infarction (MI), hypertension, heart failure
• Other: pheochromocytoma, portal hypertension, thyrotoxicosis, glaucoma, migraine headache, anxiety

Beta-Blockers Side Effects

• Heart: bradycardia, heart block, angina pain
• Other: cold extremities, intermittent claudication, acute bronchial asthma

Beta-Blockers Contraindications

• Heart: bradycardia (< 60 bpm), heart block, advanced stages of heart failure, vasospastic angina.
• Other: bronchial asthma, diabetic patients, pregnancy

MCQs

• Adrenaline addition to local anaesthetics: delays absorption, prolongs duration, and reduces toxicity
• Physiological antagonist of adrenaline: acetylcholine
• Beta-blockers use: hypertension, heart block, angina