Compare and contrast the pharmacology of noradrenaline, vasopressin and phenylephrine when used as vasopressors in the critically ill.
Noradrenaline is the catecholamine released by postganglionic adrenergic nerves. Direct agonist acting on alpha (vasoconstrictor: arterial and venous) and beta-1 (contractility, pro-arrhythmic) adrenergic receptors. Not absorbed enterally. Rapidly metabolised by COMT and MAO, resulting short (minutes) duration of effect (usually administered as intravenous infusion into central vein at rate of 0.5 to 100 mcg/min). Used clinically to increase blood pressure (usually in the setting of vasodilatory shock).
Vasopressin is a hormone/neurotranmitter with a complex series of effects. Direct action on a number of receptors (V1 (vascular: vasoconstriction), V2 (renal: anti-diuresis), V3 (pituitary), OTR (oxytocin receptor subtypes) and P2 (purinergic). Not absorbed enterally. Rapidly inactivated by trypsin and peptidases, resulting in short (minutes) duration of effect (longer on kidneys as very low concentration are required). Used clinically as treatment for diabetes insipidus (IM, IV or
intranasal), and more recently by intravenous infusion (via central vein at rates of 0.01 to 0.1
U/min) to increase blood pressure (usually in the setting of vasodilatory shock) or as a large intravenous bolus providing potent vasoconstriction during cardiac arrest (40 units). Potentiates the action of other vasoconstrictor agents.
Phenylephrine is a synthetic alpha-1 adrenoreceptor agonist, similar in structure to adrenaline. Not administered enterally, biotransformation not well described (not metabolised by COMT) but duration of action longer than naturally occurring catecholamines (still minutes). Used clinically for vasoconstrictor effects, usually administered intravenously either in small bolus doses or occasionally as an intravenous infusion (via a central vein at rates of 40 to 180 mcg/min).
Refractory hypotension may respond to agents with combined alpha-1 & alpha-2 activity (e.g. noradrenaline).
Great masses of text in homage to noradrenaline and vasopressin are available elsewhere. Phenylephrine is less common.
|
Features |
Noradrenaline |
Phenylephrine |
Vasopressin |
|
Class |
Endogenous catecholamine |
Synthetic catecholamine |
Endocrine nonapeptide |
|
Pharmacokinetics |
Half-life 2-3minutes |
Half-life 5-10 minutes |
0.002 units /kg/min; or, 2-2.4 units/hr |
|
Receptor activity |
Predominantly alpha-1 agonist activity; Affinity for receptors decreases in acidosis |
Strongly selective for alpha-1 receptors Affinity for receptors decreases in acidosis |
Acts on V1 receptors (for vasopressor activity) and on V2 receptors (for antidiuretic activity). |
|
Mechanism |
Increases intracellular IP3, which in turn increases the availablility of intracellualr calcium to smooth muscle contractile proteins |
Increases intracellular IP3, which in turn increases the availablility of intracellualr calcium to smooth muscle contractile proteins |
V1 effect is by Gq-protein coupled receptors, which also increases intracellular IP3. |
|
Clinical effects |
Arterial and venous vasoconstriction |
Arterial and venous vasoconstriction |
Arterial and venous vasoconstriction |
For those (like me) who are unfamiliar with phenylephrine, there is an excelent monograph on its properties published by Schering-Plough (it is the Briefing Document for NDAC Meeting in December 14, 2007)