Pharmacology of Adrenaline

Adrenaline

• Adrenaline's effects include vasoconstriction (alpha receptors), increased systolic blood pressure (beta 1 receptors), and decreased diastolic blood pressure (beta 2 receptors).
• Adrenaline causes mydriasis (pupil dilation) by stimulating alpha 1 receptors in the radial muscles of the eye.
• Adrenaline is a powerful bronchodilator, acting on beta 2 receptors in the bronchioles.
• Adrenaline inhibits both tone and motility in the gastrointestinal tract.
• In the urinary bladder, adrenaline relaxes the detrusor muscle (beta 2 receptors) and contracts the sphincter (alpha 1 receptors), causing urine retention.
• Adrenaline relaxes the pregnant human uterus (beta 2 receptors).
• Adrenaline increases blood glucose levels through hepatic glycogenolysis (beta 2 receptors) and lipolysis (beta 3 receptors), leading to increased oxygen consumption.
• Adrenaline has weak stimulant effects on the central nervous system, potentially causing restlessness, headache, and tremors.
• Adrenaline facilitates neuromuscular transmission and hastens muscle recovery from fatigue by increasing blood flow.
• Adrenaline is the physiological antagonist of histamine.
• Therapeutic uses of Adrenaline include treatment of acute bronchial asthma, anaphylactic shock, allergy, urticaria, and as a local hemostatic agent.
• Contraindications for Adrenaline use include coronary heart disease, hypertension, and patients receiving digitalis.

Noradrenaline

• Noradrenaline is released by postganglionic adrenergic nerves and is a strong vasoconstrictor.
• Noradrenaline stimulates alpha receptors, as well as beta 1 and beta 2 receptors to a lesser degree.
• Noradrenaline's cardiovascular effects include a positive inotropic effect on the heart, slight changes in cardiac output, vasoconstriction in skin and mucous membranes, increased total peripheral resistance, and an increase in both systolic and diastolic blood pressure.

Isoprenaline (Non selective B agonist)

• Isoprenaline primarily stimulates beta adrenergic receptors, with minimal effect on alpha receptors.
• Isoprenaline increases heart rate, force of contraction, and cardiac output.
• Isoprenaline causes dilation of skeletal muscle blood vessels, leading to decreased peripheral resistance and diastolic blood pressure.
• It is not destroyed by MAO and has a longer duration of action than catecholamines.

Ephedrine

• Ephedrine is a mixed adrenergic agonist and has local and systemic effects.
• Locally, it acts as a hemostatic and decongestant.
• Systemically, Ephedrine causes vasoconstriction, increasing both systolic and diastolic blood pressure.
• Ephedrine relaxes the urinary bladder's detrusor muscle and contracts the sphincter, causing bronchodilation and decongestion of the bronchial mucosa.
• Ephedrine causes mydriasis by stimulating the dilator pupillae muscle, but does not affect accommodation, intraocular pressure, or the light reflex.
• Ephedrine's actions on the central nervous system include mental alertness, anxiety, and insomnia.
• Ephedrine enhances neuromuscular transmission and reduces fatigue in skeletal muscles.
• Therapeutic uses for Ephedrine include:
  • Chronic bronchial asthma (prophylactic)
  • Nasal decongestant
  • Mydriatic
  • Prevention of blood pressure falls during spinal anesthesia
  • Nocturnal enuresis
  • Narcolepsy

Amphetamine

• Amphetamine indirectly stimulates the release of noradrenaline from sympathetic nerves.
• Amphetamine's cardiovascular effects include increased systolic and diastolic pressure with reflex bradycardia.
• Amphetamine causes mydriasis upon local application to the eye, as well as relaxation of the urinary bladder's detrusor muscle and contraction of the sphincter.
• Amphetamine has minimal action on the bronchi.
• Amphetamine stimulates:
  • Cerebral cortex
  • Reticular activating system
  • Vital medullary centers
  • Spinal cord

Receptor Selective Sympathomimetics

• Phenylephrine is a specific alpha 1 adrenergic agonist, commonly used as a nasal decongestant.
• Specific alpha 2 adrenergic agonists (clonidine, alpha-methyldopa, guanabenz) are used to treat hypertension by centrally stimulating presynaptic alpha 2 receptors, inhibiting noradrenaline release, and producing hypotension.
• Dobutamine is a specific beta 1 agonist.
• Salbutamol and Salmeterol are specific beta 2 agonists, used to treat bronchial asthma.

Alpha Adrenergic Blockers

• Alpha adrenergic blockers inhibit the effects of sympathetic nerve stimulation. Examples include:
  • Dibenamine or dibenzyline
  • Ergot alkaloids
  • Imidazoline derivatives

Beta Adrenergic Blockers

• Examples of beta adrenergic blockers include:
  • Propranolol
  • Pronethalol
  • DCI (Dichloroisopretrenol)

Side Effects of Beta Blockers

• Bronchoconstriction (severe attacks in asthmatic patients)
• Severe bradycardia
• Aggravation of heart failure
• Cold extremities and muscle fatigue due to blocking beta 2 receptors in blood vessels.
• Abrupt withdrawal of propranolol may lead to severe or rebound hypertension, so therapy should be stopped gradually.

Contraindications for Beta Blockers

• Bronchial asthma or COPD
• Congestive heart failure
• Hypotension

Adrenergic Neuron Blockers

• These drugs prevent the response to sympathetic nerve stimulation by inhibiting the release, storage, or synthesis of noradrenaline.

Drugs that Prevent Noradrenaline Release

• Guanethidine (Ismelin) & Bretylium

Therapeutic Uses of Adrenergic Neuron Blockers

• Treatment of hypertension, especially during pregnancy
• Treatment of hypertensive patients with renal insufficiency

Side Effects of Adrenergic Neuron Blockers

• Postural hypotension
• Central sedative action

Contraindications for Adrenergic Neuron Blockers

• Phaeochromocytoma
• Active liver diseases

Drugs Acting on Autonomic Ganglia

• Autonomic ganglia, both sympathetic and parasympathetic, have nicotinic receptors (NN) and transmission is mediated by acetylcholine.
• Drugs affecting autonomic ganglia impact both parasympathetic and sympathetic systems.

Ganglion Stimulants

• Stimulate nicotinic receptors in autonomic ganglia, releasing acetylcholine and noradrenaline.
• The effect depends on the predominant autonomic tone of the organ.
• Excessive use can cause sustained depolarization and transmission failure (ganglion block).
• Examples include:
  • Nicotine
  • Lobeline
  • TMA (tetramethylammonium)
  • DMPP (dimethylphenyl piperazinium)

Nicotine

• An alkaloid found in tobacco leaves.
• No therapeutic uses, primarily used as an insecticide.
• Absorbed orally, through the respiratory tract, and from the intact skin.
• Stimulates ganglia in small doses, but high doses lead to blockade.

Cardiovascular Effects of Nicotine

• Similar to sympathetic stimulation, releases adrenaline and noradrenaline from the adrenal medulla.
• Vasoconstriction, except for coronary and skeletal muscle blood vessels.
• Tachycardia
• Increased blood pressure, force of contraction, and cardiac output.

Gastrointestinal Effects of Nicotine

• Increased tone and motility of the intestine.
• Increased gastric secretion.

Central Nervous System Effects of Nicotine

• Stimulation of the CTZ (chemoreceptor trigger zone), producing vomiting.
• Small doses stimulate respiratory centers reflexly.
• Stimulation of ADH (antidiuretic hormone) release.
• Tremors and convulsions followed by depression.
• Tolerance develops with repeated administration.