PharmacologyTier 1Medical Sciences concept

Vasopressor mechanisms of action (noradrenaline, adrenaline, vasopressin)

Core concept

Two separate problems - vasoplegia (low SVR) and pump failure (low CO) - and the receptor profile decides which drug
- alpha-1 -> vascular smooth muscle Gq -> vasoconstriction -> inc SVR, inc MAP
- beta-1 -> myocardial Gs -> inc cAMP -> inotropy + chronotropy
- beta-2 -> vascular Gs -> vasodilatation; skeletal muscle, bronchi
- V1 -> Gq, catecholamine-independent vasoconstriction
MAP = CO x SVR - fix the term that is actually low

Agent	Receptors	Net effect
Noradrenaline	alpha-1 >> beta-1	inc SVR, MAP; modest inotropy, reflex bradycardia offsets chronotropy
Adrenaline	alpha-1, beta-1, beta-2 (beta at low dose, alpha at high)	inc CO and inc SVR
Vasopressin	V1 (V2 at higher dose)	Pure vasoconstriction, no beta effect, no tachyarrhythmia
Metaraminol	alpha-1, plus indirect NA release	Vasoconstriction; peripheral line-safe
Dobutamine	beta-1 >> beta-2, minimal alpha	inc contractility + rate, mild vasodilatation -> may drop BP
Dopamine	D1 (low) -> beta-1 (mid) -> alpha-1 (high)	Dose-dependent; inc arrhythmia
Milrinone	PDE3 inhibitor (not a receptor)	Inodilator, receptor-independent - works through beta-blockade
Terlipressin	V1 agonist	Splanchnic vasoconstriction -> dec portal inflow

Noradrenaline is first-line in septic shock; vasopressin added as second agent to spare catecholamine dose
Vasopressin retains effect at acidotic pH, where catecholamine receptors are downregulated
Adrenaline: inc lactate and inc glucose, dec K - through beta-2, not tissue hypoperfusion
Dobutamine lowers MAP as often as it raises it - use for low CO with adequate SVR
Terlipressin - hepatorenal syndrome (with albumin) and variceal bleeding; watch for ischaemia and hyponatraemia

Septic shock - noradrenaline first, target MAP 65 mmHg; add vasopressin, then consider adrenaline
- Add hydrocortisone if vasopressor-dependent
Cardiogenic shock - noradrenaline preferred over adrenaline (less lactate, fewer refractory-shock events); add dobutamine or milrinone for low output
Anaphylaxis - adrenaline IM 0.5 mg, alpha-1 reverses vasodilatation and oedema, beta-2 bronchodilates and stabilises mast cells
Peripheral extravasation of noradrenaline -> phentolamine infiltration
Anaerobic-threshold clue: rising lactate on adrenaline is often beta-2 driven glycolysis, not worsening shock
Never use dobutamine as the sole agent in undifferentiated hypotension

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