Neonatology
Inotropes (b -adrenergic) and Pressors (a -adrenergic)
Jon Palmer, VMD, Associate Professor, New Bolton Center, University of Pennsylvania
a 1-adrenergic effects:
Increased systemic vascular resistance (construction of smooth muscles)
Elevated systolic and diastolic blood pressure
Decreased perfusion of splanchnic, mucosal, renal, and dermal circulation
Inhibit insulin secretion
a 2-adrenergic effects:
Inhibit norepinephrine release
Negative chronotrophy
Release of growth hormone
b 1-adrenergic effects:
Increased myocardial contractility (inotropic)
Increased heart rate (chronotropic)
Increased conduction velocity through the atrioventricular node
Myocardial irritability
Enhance renin secretion
Lipolysis
b 2-adrenergic effects:
Relaxation of smooth muscle - vasodilation
Relaxation of skeletal muscle vasculature
Relaxation of smooth muscle in bronchi - bronchodilation
Enhance glucagon secretion - glycogenolysis
Hypokalemia
D1 Dopaminergic receptors
Post synaptic active relaxation of smooth muscles in vascular beds
Stimulate increased renal, splanchnic, cerebral and corinary blood flow through active vasodilation.
D2 Dopaminergic receptors
Inhibits release of prolactin
Inhibit release of b -endorphin
Inhibits release of thyrotropin, aldosterone
Direct renal tubular affect causing naturesis
Sympathetic control of vascular resistance is maintained by the vasomotor center of the lower pons and medulla. Constant sympathetic tone maintains vascular tone at approximately 50% construction allowing for both increase and decrease in vasomotor activity in response to physiologic changes in cardiovascular status. Exogenous catecholamines override this control with direct stimulation of adrenergic receptors increasing sympathetc tone.
Inotropes (b -adrenergic)
Dobutamine
Epinephrine
Isoproterenol (mild vasodilation - b 2)
Norepinephrine + phentolamine
Nitroprusside + (norepinephrine or epinephrine or dopamine)
Pressors (a -adrenergic)
Phenylephrine
Norepinephrine
Mixed agents (a -adrenergic, b -adrenergic)
Dopamine
Epinephrine
Vasodilators (afterload reducers)
Nitroprusside (primarily systemic vasodilator)
Nitroglycerin (primarily pulmonary vasodilator)
Phentolamine
Dobutamine has primarily b 1 at low to moderate doses and thus is a good inotrope. In man some a 2 activity may result in mild vasodilation but in general a 1and a 2 stimulus is well balanced so that clinically they are not important. In adult horses a 1 activity appears as the dose increases causing significant vasoconstriction.
Dopamine has dopaminergic activity at low doses, b 1 & b 2 activity at moderate doses, and a 1 activity at high doses. It causes norepinephrine release from nerve terminals which has lead to the suggestion that this is its major mode of action at high doses and the suggested limitation in critical patients who become depleted. At doses over 20 µg/kg/min intrapulmonary shunting may occur and so limits its dosage (dobutamine dose not have this limit and is sometime given in doses as high as 40-50 µg/kg/min).
Epinephrine has a 1, a 2, b 1, b 2 activity; Beta activity is predominant resulting in increased cardiac output and decreased peripheral resistance at low doses. It has been associated with hyperglycemia, hypokalemia, lipolysis, and increased platelet aggregation. It's affect on renal function is controversial.
Norepinephrine has a 1 and b 1 activity but variable b 2 activity resulting in potent vasopressor activity; it as both inotropic and chronotropic activities but its chronotropic affect is usually blunted by vagal reflex slowing the heart rate induced by the rise in blood pressure. There is an increase in myocardial oxygen consumption due to cardiostimulation and increased afterload.
Relative Potency of Inotropes and Pressors
Drug |
Infusion Rate* |
a Effect (Pressor) |
b Effect (Inotropic) |
Use |
| Dopamine | 1 - 5 µg/kg/min (dopaminergic effect) 5 - 15 µg/kg/min 10 - 20 µg/kg/min |
+ ++ +++ |
+ ++ ++ |
1st line choice, good mixed a and b response |
| Dobutamine | 2 - 20 µg/kg/min (high doses) |
+ (++) |
+++ |
good b effects; |
| Epinephrine | 0.1-1µg/kg/min (max 3 µg/kg/min) |
++ |
+++ |
use if not responding to dopamine; good mixed a and b response |
| Norepinephrine | 0.05 - 1 µg/kg/min (max 2 µg/kg/min) |
+++ |
+ |
primarily a effect; should be combined with a b drug |
| Phenylephrine | 0.1 - 1 µg/kg/min |
+++ |
0 |
primarily a effect; should be combined with a b drug |
* These rate serve as guidelines for therapy. The pharmacokinetics of these drugs are not consistent between individuals and within the same foal overtime. For this reason, the dose must be titrated for the individual and may need to be adjusted over time.