vasoactive drugs summary

receptor physiology

receptor	location	physiologic effect
$α_{1}$	Vascular smooth muscle	Vasoconstriction ( $↑$ SVR $\to$ $↑$ MAP)
$β_{1}$	Cardiomyocytes	Inotropy ( $↑$ contractility) & Chronotropy ( $↑$ HR)
$β_{2}$	Vascular smooth muscle / Lungs	Vasodilation & Bronchodilation
$V_{1}$	Vascular smooth muscle	Vasoconstriction (independent of pH/catecholamines)
$A T_{1}$	Vascular smooth muscle	Vasoconstriction (via RAAS pathway)
$D_{1}$	Renal/Splanchnic vessels	Vasodilation (clinical significance debated)

drug	class	1° receptors	physiologic effect	clinical niche
Norepinephrine	Pressor / Inotrope	$α_{1}$ +++, $β_{1}$ ++	$↑$ MAP, $↑$ SVR, $\leftrightarrow$ CO	First-line workhorse. Sepsis, cardiogenic, undifferentiated shock.
Epinephrine	Pressor / Inotrope	$α$ +++, $β$ +++	$↑$ MAP, $↑$ CO, $↑$ HR	First-line: Anaphylaxis, Code Blue. Rescue: Sepsis (watch for lactate rise).
Vasopressin (ADH)	Pressor	$V_{1}$	$↑$ MAP, $↑$ SVR, $\leftrightarrow$ / $d o w na rro w$ CO	Second-line: Sepsis (sparing agent). Fixed dose (0.04 U/min or 2.4 U/hr).
Phenylephrine (Neo-Synephrine)	Pressor	$α_{1}$ ++++	$↑$ MAP, $↑$ SVR, $↓$ CO, $↓$ HR	Anaesthesia, tachyarrhythmias. Avoid in heart failure (increases afterload).
Dopamine	Pressor / Inotrope	Dose Dependent ( $a lp ha$ , $β$ , $D$ )	$↑$ MAP, $↑$ HR, $↑$ CO	3rd Line/Historical. High risk of arrhythmia. Sometimes used in bradycardia.
Isoproterenol	Chronotrope	$β_{1}$ +++, $β_{2}$ +++	$↑↑$ HR, $↑$ CO, $↓$ SVR	Bradyarrhythmias, Heart Transplant (denervated heart).
Dobutamine	Inodilator	$β_{1}$ ++, $β_{2}$ +	$↑$ CO, $↓$ SVR, $↓$ PCWP	Cardiogenic shock, sepsis with cardiomyopathy. Risk of tachycardia.
Milrinone	Inodilator	PDE3 Inhibitor	$↑$ CO, $↓↓$ PVR, $↓$ SVR	RV Failure, beta-blocked patients. Long half-life (renal dosing).
Levosimendan	Inodilator	Ca-Sensitizer	$↑$ CO, $↓$ SVR	Beta-blocked patients. Long-acting metabolites.

The 65 Trial (Lamontagne et al., JAMA 2020): In patients aged $\geq$ 65 with chronic hypertension, a permissive MAP target of 60–65 mmHg was non-inferior to standard care and resulted in lower vasopressor exposure.
Standard Target: Target MAP $\geq$ 65 mmHg for most patients.

Receptor Synergism: Targeting different receptors ( $a lp h a_{1}$ , $V_{1}$ , $A T_{1}$ ) allows for dose reduction of individual agents.
Decatecholaminisation: Early initiation of non-catecholamine agents helps mitigate toxicity (arrhythmias, immunomodulation) associated with high-dose adrenergic stimulation.
Early Vasopressin: Adding Vasopressin (ADH) when Norepinephrine doses reach 0.25–0.5 µg/kg/min is supported to prevent refractory shock (SSC Guidelines).

Tachyphylaxis: Catecholamine agents (e.g., Norepinephrine, Epinephrine, Dopamine) are subject to tachyphylaxis over time, requiring escalating doses. Non-catecholamine inodilators like Milrinone do not exhibit tachyphylaxis.
Peripheral Administration: Vasopressors can be administered via a large peripheral vein (proximal to antecubital fossa) for a short duration while establishing central access.
The “Renal Dose” Myth: Low-dose dopamine does not protect renal function and should not be used for this indication.
Phenylephrine & Reflex Bradycardia: Due to selective $a lp ha$ -receptor stimulation, phenylephrine can induce baroreceptor-mediated reflex bradycardia and reduction in Cardiac Output.
- Septic Shock: Generally second-line. Useful if the patient has severe tachyarrhythmias (as it doesn’t increase HR), but less ideal than norepinephrine for preserving tissue perfusion.
- Cardiogenic Shock: Avoid. The increase in afterload without inotropy can worsen heart failure.

Septic Shock: Norepinephrine $\to$ Add Vasopressin (ADH) (at 0.25-0.5 mcg/kg/min) $\to$ Add Epinephrine or Angiotensin II.
Cardiogenic Shock: Norepinephrine (restore MAP) $\pm$ Dobutamine/Milrinone (restore flow).
Anaphylactic Shock: Epinephrine (stops mast cell degranulation via $b e t a_{2}$ stabilisation).