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PH2.{1,3} | PH2.{1,3} | Adrenergic Drugs and Emergency Sympathomimetic Use — SDL Guide — SDL Guide

Learning Objectives

• Describe the types, pharmacokinetics, pharmacodynamics, therapeutic uses, and adverse drug reactions of adrenergic and antiadrenergic drugs (PH2.1)
• Explain the rationale for and demonstrate the emergency use of sympathomimetic and parasympatholytic drug agonists/antagonists (adrenaline, noradrenaline, dopamine, dobutamine, atropine) in case-based scenarios (PH2.3)

INSTRUCTIONS

The adrenergic nervous system is the pharmacological substrate for managing life-threatening emergencies: anaphylaxis, cardiac arrest, septic shock, and acute heart failure all require you to select the correct catecholamine or adrenergic agent, dial in the right dose and route, and understand why it works. This guide takes you from receptor physiology through drug classification to bedside decision-making, giving you the pharmacological framework that underpins ACLS, ICU vasopressor protocols, and anaesthetic emergency drills.

References

• KD Tripathi, Essentials of Medical Pharmacology, 8th ed., Ch 9-10 (textbook)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th ed., Ch 12-13 (textbook)

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Version 2.0 | NMC CBUC 2024

Pathophysiology of Sympathetic Activation and Adrenergic Receptors

The adrenergic system is activated by stress, haemorrhage, hypoglycaemia, or threat — the classic 'fight-or-flight' response. Catecholamines are synthesised from tyrosine via a four-step pathway: tyrosine → DOPA (tyrosine hydroxylase, rate-limiting) → dopamine → noradrenaline → adrenaline (phenylethanolamine N-methyltransferase, in adrenal medulla only). Released catecholamines interact with adrenoceptors on target cells, producing effects that are entirely predictable once you know which receptor family is engaged.

The receptor landscape in clinical practice:

• α1 receptors: smooth muscle of blood vessels (vasoconstriction → ↑BP), iris dilator, sphincters. Gq → IP3/DAG → intracellular Ca²⁺ → contraction.
• α2 receptors: presynaptic nerve terminals (autoreceptors: ↓NA release = negative feedback); postsynaptic in CNS and platelets.
• β1 receptors: heart (↑HR, ↑force), kidney juxtaglomerular cells (↑renin). Gs → adenylyl cyclase → ↑cAMP → PKA.
• β2 receptors: bronchial smooth muscle (relaxation → bronchodilation), uterus (relaxation), vascular smooth muscle of skeletal muscle (vasodilation), liver (glycogenolysis).
• β3 receptors: adipose tissue (lipolysis), detrusor muscle (relaxation).
• D1/D2 receptors: renal + splanchnic vasculature (vasodilation at low dopamine concentrations).

The baroreceptor reflex is a critical modulator: when a drug raises BP via α1 stimulation (e.g. phenylephrine), baroreceptors fire → parasympathetic surge → reflex bradycardia. This predictable reflex is why phenylephrine must be given with awareness of its heart-rate lowering effect.

Adrenergic Receptor Subtypes: Locations and Effector Responses

Therapeutic Rationale for Adrenergic Drug Therapy

The fundamental rationale for manipulating the adrenergic system is to restore or re-calibrate the physiological variables that sustain tissue perfusion and organ function. In critical illness, the normal sympathetic compensatory response is either inadequate (septic shock — vasodilation overwhelms the reflex) or pathologically excessive (hypertensive crisis — sympathetic hyperactivation). Understanding which physiological defect is present determines which receptor targets are engaged and which drugs are chosen.

Key therapeutic goals mapped to receptor targets:

• Restore perfusion pressure (septic/distributive shock): noradrenaline (α1 + β1) is first-line — raises SVR and provides modest inotropy without the excessive chronotropy of adrenaline.
• Treat anaphylaxis (bronchospasm + vasodilation + urticaria): adrenaline is uniquely indicated — β2 dilates bronchi, α1 constricts cutaneous vasculature, β1 supports cardiac output. No other drug addresses all three pathways simultaneously.
• Support cardiac output (acute decompensated heart failure): dobutamine (selective β1) increases contractility without major vasoconstriction; dopamine at low doses adds D1-mediated renal vasodilation.
• Control bronchospasm (asthma/COPD): salbutamol (β2 agonist) relaxes bronchial smooth muscle with minimal β1 cardiac effects (at therapeutic doses).
• Lower BP (hypertension, angina, post-MI): beta-blockers (β1 blockade → ↓HR, ↓CO, ↓renin) and alpha-blockers (α1 blockade → ↓SVR).
• Manage phaeochromocytoma (catecholamine excess): phenoxybenzamine (irreversible α-blocker) pre-operatively, then beta-blockers only after alpha-blockade (beta first → unopposed α1 → hypertensive crisis).

The key discipline: always match the receptor to the physiological defect. Using a non-selective agonist when a selective one would suffice risks unwanted receptor activation and predictable adverse effects.

Classification of Adrenergic Drugs

Adrenergic drugs are classified at two levels: first by their primary action (agonist vs antagonist), then by their receptor selectivity and mechanism. Understanding this taxonomy is essential for predicting the pharmacological profile of any agent in the class.

Class 1: Adrenergic Agonists (Sympathomimetics)

Agonists mimic or enhance sympathetic activity. They are further divided by mechanism:
- Direct-acting: bind adrenoceptors directly. Examples: adrenaline (non-selective), noradrenaline (α1/α2/β1), dopamine (dose-dependent), dobutamine (selective β1), phenylephrine (selective α1), salbutamol (selective β2), isoprenaline (non-selective β).
- Indirect-acting: promote NA release from nerve terminals or inhibit NA reuptake (no direct receptor binding). Examples: amphetamine, tyramine.
- Mixed action: both direct receptor binding and NA release. Example: ephedrine — clinically relevant as a vasopressor in spinal anaesthesia-induced hypotension.

Class 2: Adrenergic Antagonists (Sympatholytics)

Antagonists block adrenoceptors. Classified by receptor subtype:
- Alpha-blockers:
- Non-selective irreversible: phenoxybenzamine (covalent bond → 24h block → used in phaeochromocytoma prep)
- Non-selective reversible: phentolamine (used in phaeochromocytoma crisis, IV)
- Selective α1: prazosin, terazosin, doxazosin (used in hypertension, BPH — first-dose hypotension is a key adverse effect)
- Beta-blockers:
- Non-selective (β1+β2): propranolol — avoid in asthma (β2 blockade → bronchoconstriction)
- Selective β1 (cardioselective): atenolol, metoprolol, bisoprolol — preferred in patients with reactive airway disease
- Mixed α + β blocker: carvedilol, labetalol — carvedilol used in HFrEF (reduces mortality); labetalol preferred in hypertensive emergencies in pregnancy

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