Adrenergic Agonists

Adrenergic agonists mimic noradrenaline and adrenaline at alpha and beta adrenergic receptors. Their effects depend on receptor selectivity, route and whether they act directly or indirectly. They are used for shock, anaphylaxis, cardiac arrest, bronchospasm, hypotension, nasal congestion, ocular disease and bladder dysfunction.

Classification by structure. Catecholamines (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline) have a short half-life and no oral activity because of COMT and MAO. Non-catecholamines (phenylephrine, ephedrine, salbutamol, midodrine) are longer acting and often orally active.

Classification by receptor. Alpha-1 agonists: phenylephrine, midodrine. Alpha-2 agonists: clonidine, dexmedetomidine, brimonidine. Beta-1 predominant: dobutamine. Beta-2 selective: salbutamol, terbutaline, formoterol, salmeterol. Beta-3: mirabegron. Mixed: adrenaline, noradrenaline, dopamine, ephedrine, isoprenaline.

Receptor signalling. Alpha-1 couples to Gq and causes vasoconstriction, pupil dilation and bladder neck contraction. Alpha-2 couples to Gi and inhibits noradrenaline release, reduces central sympathetic outflow and inhibits insulin release. Beta-1 and beta-2 couple to Gs and raise cyclic AMP. Beta-1 increases rate, contractility, conduction and renin release. Beta-2 causes bronchodilation, skeletal muscle vasodilation, uterine relaxation, glycogenolysis and potassium shift into cells. Dopamine D1 receptors vasodilate renal and mesenteric vessels.

Pharmacokinetics. Adrenaline and noradrenaline have plasma half-lives of 2 to 3 minutes, so they require continuous intravenous infusion when sustained effect is needed. Intramuscular adrenaline peaks within minutes and is the route of choice in anaphylaxis, preferably in the anterolateral thigh.

Tolerance. Prolonged exposure causes receptor desensitisation and downregulation (tachyphylaxis), most marked at beta-2 receptors, and loss of effect in acidosis.

• Adrenaline: alpha and beta; low doses favour beta, high doses alpha. Used in anaphylaxis, cardiac arrest, severe asthma, and as an infusion in refractory shock.
• Noradrenaline: mainly alpha-1 with beta-1; first-line vasopressor in septic shock.
• Dopamine: dose-dependent D1, beta-1 then alpha-1 effects. Arrhythmias are more frequent than with noradrenaline.
• Dobutamine: beta-1 predominant; raises output with vasodilation; used in low output states.
• Isoprenaline: non-selective beta; chronotropic and vasodilator.
• Phenylephrine, midodrine: pure alpha-1; vasoconstriction without cardiac stimulation.
• Salbutamol, terbutaline, formoterol, salmeterol: beta-2 bronchodilators.
• Ephedrine: direct and indirect release; oral and parenteral.

• Anaphylaxis: adrenaline 500 micrograms (0.5 mL of 1 mg/mL) intramuscularly for adults and children over 12 years, 300 micrograms for ages 6 to 12 years, 150 micrograms under 6 years, repeated after 5 minutes if needed.
• Cardiac arrest: adrenaline 1 mg intravenously every 3 to 5 minutes.
• Septic shock: noradrenaline infusion titrated to a mean arterial pressure of about 65 mmHg. Dopamine is an alternative only in selected patients with low arrhythmia risk. Use central access where possible.
• Cardiogenic shock with low output: dobutamine 2.5 to 20 micrograms/kg/minute.
• Bradycardia with haemodynamic compromise: isoprenaline 2 to 10 micrograms/minute while pacing is arranged.
• Bronchospasm: salbutamol by nebuliser or inhaler. Intravenous salbutamol is reserved for severe cases.
• Selection: choose by dominant haemodynamic problem. Vasodilatory shock needs alpha-1 effect, low output needs beta-1, anaphylaxis and arrest need adrenaline.

Contraindications and cautions. Tachyarrhythmia, phaeochromocytoma, hypertensive crisis, narrow-angle glaucoma and unopposed use in hypovolaemia. Halogenated anaesthetics sensitise the myocardium to arrhythmia from catecholamines.

Adverse effects. Tachycardia, arrhythmia, hypertension, myocardial ischaemia, tremor, anxiety, hypokalaemia, hyperglycaemia, lactic acidosis (a beta-2 effect, seen with adrenaline and high-dose salbutamol), peripheral and splanchnic ischaemia, and tissue necrosis on extravasation.

Extravasation. Stop the infusion, aspirate through the cannula, and infiltrate phentolamine 5 to 10 mg diluted in 10 mL of 0.9% sodium chloride around the site.

Interactions. Monoamine oxidase inhibitors and tricyclic antidepressants potentiate indirect and some direct agents. Non-selective beta blockers cause unopposed alpha effect with adrenaline, producing severe hypertension and reflex bradycardia. Glucagon 1 to 5 mg intravenously can overcome beta blocker resistance in anaphylaxis. Antagonised by alpha and beta blockers.

Monitoring. Continuous electrocardiography and arterial pressure for infusions, lactate, potassium, glucose, urine output and peripheral perfusion.

Referral and escalation. Any vasopressor or inotrope infusion requires critical care or high dependency level monitoring.

Special groups. Pregnancy: phenylephrine is used for spinal hypotension at caesarean section. Children: use weight-based doses and age-specific adrenaline volumes. Older adults: higher risk of arrhythmia and ischaemia.