Adrenergic Agonists (Sympathomimetics): Adrenaline & the Selective Agonists
One drug can restart a stopped heart, reverse a deadly allergic reaction, and open a suffocating asthmatic's airways — all at once — because it presses every sympathetic button in the body. Its more refined cousins press just one button each: only the airways, only the heart, only the blood vessels. Master which agonist hits which receptor, and you can summon 'fight-or-flight' in whatever precise dose a patient needs.
At a birthday party, a boy bites into a cookie with hidden peanuts and within minutes his lips swell, his throat tightens, hives spread across his skin, and his blood pressure crashes — anaphylaxis. His mother jabs an auto-injector into his thigh, and one drug pulls him back from the edge: his airways reopen, his blood pressure climbs, and the swelling eases. That drug is adrenaline, and it saves him because it hits several sympathetic receptors at once — each doing a different, life-saving job. It's the perfect introduction to how adrenergic agonists work.
Direct agonists: pressing the receptor itself
Sympathomimetics mimic noradrenaline and adrenaline. A direct-acting adrenergic agonist binds an adrenergic receptor and switches it on, producing whatever that receptor does. The art is selectivity — which receptor(s) a drug hits. The broad, non-selective agents hit many: adrenaline (epinephrine) activates α and β receptors together (anaphylaxis, cardiac arrest, and added to local anaesthetics to constrict vessels), while noradrenaline (norepinephrine) is a powerful vessel-constrictor (α1) used to raise blood pressure in shock. From there, the selective agonists each target one job.
Learn the selective agonists by their receptor. α1 agonists (phenylephrine, oxymetazoline) constrict vessels — used as nasal decongestants, to dilate the pupil, and to raise a low blood pressure. α2 agonists are the surprise: because α2 is a feedback brake in the brain, stimulating it REDUCES sympathetic outflow, so clonidine and methyldopa LOWER blood pressure (methyldopa is a go-to in pregnancy). β1 agonists (dobutamine) strengthen the failing heart in cardiogenic shock. β2 agonists (salbutamol/albuterol, salmeterol, terbutaline) relax the airways — the reliever inhalers of asthma. And a β3 agonist (mirabegron) relaxes the bladder for overactive bladder.
Adrenaline reverses anaphylaxis on three fronts at once: its α1 action constricts blood vessels to restore the collapsing blood pressure and reduce swelling; its β1 action supports the heart; and its β2 action relaxes the airways so he can breathe. No single-receptor drug could do all three — which is exactly why adrenaline, the non-selective agonist, is THE first-line treatment for anaphylaxis, given into the muscle of the thigh.
- Adrenaline (α+β) = anaphylaxis, cardiac arrest; noradrenaline (α1) = vasopressor in shock.
- α1 agonists (phenylephrine) constrict vessels: decongestant, mydriatic, pressor.
- α2 agonists (clonidine, methyldopa) LOWER blood pressure via central feedback.
- β1 agonist dobutamine supports the heart; β2 agonists (salbutamol) relieve asthma.
- β3 agonist (mirabegron) treats overactive bladder.
Indirect and mixed agonists
Not every sympathomimetic touches the receptor directly. Indirect-acting agonists raise noradrenaline in the synapse instead: amphetamine and tyramine force stored noradrenaline out, while cocaine blocks its reuptake — both leaving more transmitter to stimulate the receptors (recall the previous article). Ephedrine and pseudoephedrine are mixed — they both release noradrenaline and directly stimulate receptors, which is why pseudoephedrine is a common oral decongestant. Because these drugs rely on the body's own noradrenaline, their effect is broad and less controllable — and amphetamine-type stimulants carry the sympathetic side effects and abuse potential you'd expect from flooding the whole system.
Selectivity is dose-dependent — it can be lost. A β2-selective asthma reliever like salbutamol is chosen to open airways without racing the heart, but at high doses it 'spills over' onto β1 and causes tremor and palpitations. Likewise, adrenaline's balance of α and β effects shifts with dose. 'Selective' means selective at normal doses; push hard enough and the other receptors join in.
- Expecting α2 agonists to raise blood pressure. Centrally, they LOWER it (clonidine, methyldopa).
- Using a β2 reliever and being surprised by tremor/palpitations at high doses (β1 spillover).
- Giving repeated topical decongestants (oxymetazoline) for days — rebound congestion.
- Reaching for a single-receptor drug in anaphylaxis. Only adrenaline covers α, β1, and β2 together.
Which agonist and receptor combination correctly relieves an acute asthma attack?
- Sympathomimetics mimic adrenaline/noradrenaline; effect depends on which receptor.
- Adrenaline (α+β) is first-line for anaphylaxis; noradrenaline (α1) is a shock vasopressor.
- α1 → decongest/pressor; α2 → lower BP; β1 → heart; β2 → asthma; β3 → bladder.
- Indirect agonists (amphetamine, cocaine, ephedrine) raise the body's own noradrenaline.
- Katzung BG. Basic & Clinical Pharmacology — Adrenoceptor-activating (sympathomimetic) drugs.
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Adrenergic agonists.
- Rang HP, Dale MM, et al. Rang & Dale's Pharmacology — Adrenergic (sympathomimetic) agonists.
- Whalen K. Lippincott Illustrated Reviews: Pharmacology — Adrenergic agonists.
- Resuscitation & anaphylaxis guidelines — Adrenaline in anaphylaxis, cardiac arrest & shock.
