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Adrenergic Receptor Subtypes and Signaling
TEXTPharmacology II · 8 min read
α1, α2, β1, β2, β3 — knowing which receptor each pressor hits explains every hemodynamic decision in the OR.
After this lesson you can
2 min read7 sections- Map receptors (α1, α2, β1, β2, β3, D1) to tissue + effect.
- Match drugs to receptor profile.
- Predict side effects from receptor activity.
- Recall agonist + antagonist examples.
α1 receptors
- arteriolar smooth muscle
- venous capacitance vessels
- sphincters (GI/GU)
- iris dilator
- salivary glands
- vasoconstriction (↑SVR, ↑BP)
- pupil dilation
- urinary retention
- phenylephrine (pure α1)
- norepinephrine (α1 + β1)
- epinephrine high-dose (α1 dominant)
α2 receptors
- sedation
- analgesia
- decreased SVR + HR
Clinical agents: clonidine (220:1 α2:α1), dexmedetomidine (1620:1 α2:α1 — more selective).
- cooperative sedation
- sympatholysis for cardiac/vascular surgery
- opioid-sparing analgesia
- ICU sedation
- shivering treatment
β1 receptors
Located in heart (SA node, AV node, ventricles), kidney (renin release).
- positive inotropy (force)
- chronotropy (rate)
- dromotropy (conduction)
- lusitropy (relaxation)
- dobutamine (β1 dominant)
- low-dose epinephrine
- isoproterenol (β1+β2)
Beta-blockers (esmolol, metoprolol, propranolol) oppose these effects.
β2 receptors
Bronchial smooth muscle (relaxation = bronchodilation), uterine smooth muscle (relaxation = tocolysis), skeletal muscle arterioles (vasodilation), liver (glycogenolysis), pancreas (insulin release).
Activation drops K⁺ via Na/K-ATPase activation (intracellular shift).
β3 receptors
Less clinical relevance for anesthesia day-to-day.
Drug: mirabegron for OAB. β3 stimulation also linked to brown adipose thermogenesis in neonates — relevant context for understanding pediatric heat regulation.
Dose-dependent epinephrine
Mid (2-10 mcg/min): β1 dominant — increased CO + HR.
High (>10 mcg/min): α1 dominant — vasoconstriction + SVR rise.
Same molecule, different occupancy by dose.
Used clinically across this spectrum: anaphylaxis (titrated 10-100 mcg IV), cardiac arrest (1 mg q3-5 min), post-CPB low cardiac output (infusion mid-range).
Receptor mapping clinical pressors
Norepinephrine: α1 + β1 ↑SVR + modest inotropy.
Epinephrine: α1 + β1 + β2 dose-dependent.
Dopamine: D1 (low <3) + β1 (mid 3-10) + α1 (high >10).
Vasopressin: V1 receptor (not adrenergic) ↑SVR via Gq, bypasses catecholamine-resistant states (ACE-I, sepsis).
Knowing the receptor tells you the predicted side effects.
⚠ Common pitfalls
- Calling phenylephrine 'inotrope' — pure α; raises BP via SVR, may drop CO.
- Forgetting β2 bronchodilation → albuterol for asthma intra-op.
- Using dopamine routinely as 'renal dose' — outdated; no benefit.
- Confusing α2 effects (sedation via CNS) with peripheral α1 (vasoconstriction).
💎 Clinical pearls
- Norepi = α1 + β1; epi = α1 + β1 + β2; phenylephrine = pure α1; dobutamine = β1 > β2.
- Esmolol short half-life (~9 min) makes it the OR β-blocker of choice.
- Dexmedetomidine = α2 agonist → sedation + analgesia + sympatholysis without respiratory depression.
- Mixed β-blocker (carvedilol, labetalol) blocks β1 + β2 + α1 — useful in hypertensive urgency.
Recap
- Norepi = α1 + β1; epi = α1 + β1 + β2; phenylephrine = pure α1; dobutamine = β1 > β2.
- Esmolol short half-life (~9 min) makes it the OR β-blocker of choice.
- Dexmedetomidine = α2 agonist → sedation + analgesia + sympatholysis without respiratory depression.
- Mixed β-blocker (carvedilol, labetalol) blocks β1 + β2 + α1 — useful in hypertensive urgency.
Mark each section done to complete the module.