Pharmacology chapters
Adrenergic agonists and blockers
Drugs acting on the sympathetic system: adrenergic receptors and their effects, catecholamines (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline), selective agonists (salbutamol, phenylephrine, clonidine), indirect agents, alpha blockers and beta blockers with their uses, adverse effects and contraindications.
- Noradrenaline is made from tyrosine (rate-limiting enzyme tyrosine hydroxylase) and its action ends mainly by reuptake (uptake 1; blocked by cocaine and tricyclics), then MAO and COMT; receptors: α1 (Gq: vasoconstriction, mydriasis), α2 (Gi: less noradrenaline release), β1 (Gs: heart rate and force, renin), β2 (Gs: bronchodilation, vasodilation in muscle, uterine relaxation).
- Adrenaline (α and β) is the drug of choice for anaphylaxis (IM) and cardiac arrest; noradrenaline (mainly α1, β1) is the first-line vasopressor in septic shock; dobutamine (β1) boosts contractility in cardiogenic shock; dopamine acts on D1, then β1, then α1 as the dose rises; salbutamol (β2) relieves asthma; clonidine and methyldopa (central α2) lower blood pressure.
- α blockers: prazosin (α1: hypertension, BPH), tamsulosin (α1A: BPH), phenoxybenzamine (irreversible: phaeochromocytoma before surgery); β blockers: non-selective propranolol (avoid in asthma), cardioselective atenolol, metoprolol, bisoprolol; carvedilol and labetalol also block α1.
On this page
Noradrenaline: synthesis and termination
Synthesis in sympathetic nerve endings:
Tyrosine → (tyrosine hydroxylase, rate-limiting) → DOPA → (DOPA decarboxylase) → dopamine → (dopamine β-hydroxylase) → noradrenaline → (PNMT, adrenal medulla) → adrenaline
Termination:
- Reuptake into the nerve ending (uptake 1): the main way. Blocked by cocaine and tricyclic antidepressants.
- Breakdown by MAO (inside nerve endings) and COMT (in tissues); the urinary product is vanillylmandelic acid (VMA), raised in phaeochromocytoma and neuroblastoma.
Drugs acting on the nerve ending: reserpine depletes vesicle stores; guanethidine blocks release; α-methyldopa forms a false transmitter (α-methylnoradrenaline acting on central α2).
Adrenergic receptors
| Receptor | G protein | Main effects |
|---|---|---|
| α1 | Gq | Vasoconstriction (skin, gut, kidney), mydriasis (radial muscle of iris), contraction of bladder sphincter and prostate, piloerection |
| α2 | Gi | Less noradrenaline release (presynaptic), lower sympathetic outflow from the brain, less insulin release, platelet aggregation |
| β1 | Gs | ↑ heart rate (chronotropy), ↑ contractility (inotropy), ↑ AV conduction, renin release |
| β2 | Gs | Bronchodilation, vasodilation (skeletal muscle), uterine relaxation, glycogenolysis, K⁺ shift into cells, tremor |
| β3 | Gs | Lipolysis; bladder detrusor relaxation (mirabegron) |
| D1 | Gs | Renal and mesenteric vasodilation |
Adrenergic agonists
Catecholamines
| Drug | Receptors | Main uses |
|---|---|---|
| Adrenaline (epinephrine) | α1, α2, β1, β2 | Anaphylaxis (first-line, intramuscular), cardiac arrest, with local anaesthetics (vasoconstriction, longer action; avoid at fingers, toes, penis, ears, nose), severe croup (nebulised) |
| Noradrenaline (norepinephrine) | α1, α2, β1 (little β2) | Septic shock and other vasodilatory shock: first-line vasopressor. Raises BP; reflex bradycardia |
| Dopamine | D1 → β1 → α1 with rising dose | Shock with poor heart output (less used now) |
| Dobutamine | Mainly β1 | Cardiogenic shock, acute heart failure; cardiac stress testing |
| Isoprenaline | β1 and β2 | Heart block and bradycardia (temporary) |
Adrenaline effects by dose: low doses mainly β (β2 vasodilation in muscle lowers diastolic pressure); high doses add α1 vasoconstriction (BP rises).
Adrenaline 1 mg/mL (1:1000) given IM in the anterolateral thigh
Adult and child over 12: 0.5 mg = 0.5 mL of 1 mg/mL
Child 6 to 12 years: 0.3 mg = 0.3 mL
Child under 6 years: 0.15 mg = 0.15 mL
Weight-based option: 0.01 mg/kg (max 0.5 mg)
20 kg child: 0.01 × 20 = 0.2 mg = 0.2 mL of 1 mg/mL
Repeat after 5 minutes if no improvement.
1:1000 = 1 g in 1000 mL = 1 mg/mL
1:10,000 = 0.1 mg/mL (used IV in cardiac arrest: 1 mg = 10 mL)
Doses follow UK Resuscitation Council teaching; follow your hospital's current protocol.
Non-catecholamine and selective agonists
| Drug | Receptor | Uses |
|---|---|---|
| Salbutamol, terbutaline (short-acting); salmeterol, formoterol (long-acting) | β2 | Asthma and COPD; hyperkalaemia (salbutamol shifts K⁺ into cells); terbutaline and ritodrine for preterm labour (tocolysis) |
| Phenylephrine | α1 | Nasal decongestant, mydriasis without cycloplegia, hypotension during spinal anaesthesia |
| Midodrine | α1 | Orthostatic hypotension |
| Clonidine | Central α2 | Hypertension, opioid withdrawal; rebound hypertension if stopped suddenly |
| Methyldopa | Central α2 (false transmitter) | Hypertension in pregnancy; positive Coombs test, haemolytic anaemia |
| Brimonidine | α2 | Glaucoma (less aqueous production) |
| Xylometazoline, oxymetazoline | α | Nasal decongestion (rebound congestion with prolonged use) |
| Mirabegron | β3 | Overactive bladder |
Indirect-acting and mixed
- Amphetamine: releases noradrenaline and dopamine; CNS stimulant (ADHD, narcolepsy); abuse.
- Ephedrine: mixed (direct and release); tachyphylaxis; used for hypotension in spinal anaesthesia.
- Tyramine: releases noradrenaline; in cheese and fermented foods; dangerous with MAO inhibitors (hypertensive crisis).
- Cocaine: blocks reuptake; local anaesthetic with vasoconstriction; arrhythmias, MI, stroke.
Alpha blockers
| Drug | Selectivity | Uses |
|---|---|---|
| Prazosin, doxazosin, terazosin | α1 | Hypertension, benign prostatic hyperplasia (BPH) |
| Tamsulosin | α1A (prostate) | BPH; ureteric stone passage (less effect on BP) |
| Phenoxybenzamine | α1 and α2, irreversible (non-competitive) | Phaeochromocytoma (pre-operative preparation) |
| Phentolamine | α1 and α2, reversible | Hypertensive crisis from phaeochromocytoma, MAOI–tyramine reaction, cocaine; extravasation of noradrenaline |
Adverse effects: first-dose postural hypotension (give the first dose at bedtime), reflex tachycardia, nasal stuffiness, ejaculatory problems (tamsulosin), floppy iris during cataract surgery.
Adrenaline reversal: after α blockade, adrenaline lowers blood pressure because its β2 vasodilator effect is no longer opposed.
Beta blockers
| Group | Drugs | Notes |
|---|---|---|
| Non-selective (β1 + β2) | Propranolol, timolol, nadolol, sotalol | Propranolol: lipid-soluble (CNS effects); used in migraine prophylaxis, essential tremor, thyrotoxicosis symptoms, anxiety (performance), portal hypertension (variceal bleeding prevention), infantile haemangioma |
| Cardioselective (β1) | Atenolol, metoprolol, bisoprolol, esmolol (ultra-short, IV), nebivolol | Safer (but not safe) in asthma and diabetes; atenolol is water-soluble (renal excretion, fewer nightmares) |
| With α1 blockade | Labetalol, carvedilol | Labetalol: hypertension in pregnancy and hypertensive emergencies; carvedilol: heart failure |
| With partial agonist activity (ISA) | Pindolol, acebutolol | Less bradycardia |
Uses: hypertension, angina (reduce oxygen demand), after myocardial infarction (reduce mortality), heart failure (stable: bisoprolol, carvedilol, metoprolol succinate), arrhythmias (rate control in AF), glaucoma (timolol eye drops: less aqueous humour), thyrotoxicosis, migraine, tremor, anxiety.
Adverse effects: bronchospasm (asthma), bradycardia and heart block, cold hands, fatigue, masked hypoglycaemia symptoms in diabetics (tremor, palpitations), nightmares, erectile dysfunction, worsening of acute heart failure; rebound angina or tachycardia if stopped suddenly.
Contraindications: asthma (especially non-selective), heart block, severe bradycardia, decompensated heart failure, cocaine-induced chest pain (unopposed α), Prinzmetal angina.
Overdose antidote: glucagon (raises cAMP through its own receptor), with atropine and pacing.
In phaeochromocytoma, give the α blocker first (phenoxybenzamine), then add a β blocker. A β blocker alone leaves α1 vasoconstriction unopposed → hypertensive crisis.
Expect: synthesis and rate-limiting step, reuptake as the main termination, receptor effects (α1, α2, β1, β2), adrenaline in anaphylaxis (dose and route), noradrenaline in septic shock, dopamine dose effects, dobutamine, salbutamol in hyperkalaemia, clonidine rebound, methyldopa in pregnancy, α blockers in BPH and phaeochromocytoma, adrenaline reversal, β-blocker selectivity, uses, adverse effects, contraindications and glucagon in overdose.
Quick revision
- Tyrosine hydroxylase rate-limiting; reuptake ends action.
- α1 constricts; α2 reduces release; β1 heart and renin; β2 bronchi, vessels, uterus, K⁺.
- Anaphylaxis: adrenaline 0.5 mg IM (1 mg/mL) in adults.
- Septic shock: noradrenaline. Cardiogenic: dobutamine.
- Clonidine rebound; methyldopa in pregnancy; labetalol in pregnancy.
- Prazosin, tamsulosin: BPH. Phenoxybenzamine: phaeochromocytoma (α before β).
- Propranolol non-selective (avoid in asthma); atenolol, metoprolol, bisoprolol β1-selective.
- β-blocker overdose: glucagon.
Written by The House Job from standard pharmacology references (Katzung's Basic and Clinical Pharmacology).
FAQ
What is the drug of choice in anaphylaxis?
Adrenaline, given intramuscularly into the outer thigh (0.5 mg of the 1 mg/mL solution in adults), repeated after 5 minutes if needed.
Why is an alpha blocker given before a beta blocker in phaeochromocytoma?
Blocking β receptors alone removes β2 vasodilation and leaves α1 vasoconstriction unopposed, which can cause a dangerous rise in blood pressure.
Why are non-selective beta blockers avoided in asthma?
Blocking β2 receptors in the airways can cause bronchospasm.
What is adrenaline reversal?
After α blockade, adrenaline lowers blood pressure because only its β2 vasodilator effect remains.