From the Guidelines
Levophed (norepinephrine) primarily acts on alpha-1 adrenergic receptors, with some activity on beta-1 adrenergic receptors as well. When administered, norepinephrine causes potent vasoconstriction by stimulating alpha-1 receptors on vascular smooth muscle, which increases peripheral vascular resistance and raises blood pressure. This makes it particularly useful in treating hypotension and shock states. Additionally, norepinephrine has modest inotropic effects through beta-1 receptor stimulation in the heart, increasing cardiac contractility and output. Unlike other vasopressors, Levophed has minimal effect on beta-2 receptors, so it doesn't cause significant bronchodilation or vasodilation in skeletal muscle beds. The predominant alpha-1 effect explains why Levophed is particularly effective at restoring blood pressure in distributive shock states like septic shock, where vasodilation is a major problem. When administering Levophed, it's essential to monitor for potential side effects related to excessive vasoconstriction, including decreased peripheral perfusion, which can manifest as cool extremities or decreased urine output, as noted in studies such as 1. Key points to consider when using Levophed include:
- Its potent vasoconstrictive effects, which can increase blood pressure
- Its modest inotropic effects, which can increase cardiac contractility and output
- The need to monitor for potential side effects related to excessive vasoconstriction
- Its effectiveness in treating distributive shock states like septic shock, as supported by studies such as 1 and 1. Overall, the use of Levophed should be guided by the most recent and highest quality evidence, such as the 2018 study published in Intensive Care Medicine 1, to ensure optimal patient outcomes in terms of morbidity, mortality, and quality of life.
From the FDA Drug Label
CLINICAL PHARMACOLOGY LEVOPHED functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action). Levophed acts on two types of receptors:
- Alpha-adrenergic receptors: for peripheral vasoconstrictor action
- Beta-adrenergic receptors: for inotropic stimulator of the heart and dilator of coronary arteries action 2
From the Research
Receptors Activated by Levophed
Levophed, also known as norepinephrine, acts on various adrenergic receptors to produce its effects. The main receptors activated by levophed are:
- Alpha 1 (α1) adrenergic receptors: These receptors are coupled to stimulatory Gq proteins and are mainly found in the smooth muscle cells of blood vessels and urinary tract, where they induce constriction 3.
- Alpha 2 (α2) adrenergic receptors: These receptors are coupled to inhibitory Gi proteins and are mainly found in the central nervous system, where their activation results in a decreased arterial blood pressure 3, 4.
- Beta 1 (β1) adrenergic receptors: These receptors are predominantly found in the heart, where they activate the Gs-adenylyl cyclase-cAMP-protein kinase A signaling cascade, and induce positive inotropic and chronotropic effects 3.
Mechanism of Action
The activation of these receptors by levophed leads to various physiological responses, including:
- Vasoconstriction: Activation of α1 adrenergic receptors causes the contraction of smooth muscle cells in blood vessels, leading to an increase in blood pressure 3, 4.
- Decreased arterial blood pressure: Activation of α2 adrenergic receptors in the central nervous system leads to a decrease in arterial blood pressure 3, 4.
- Increased heart rate and contractility: Activation of β1 adrenergic receptors in the heart leads to an increase in heart rate and contractility 3.
Other Receptors
Levophed may also act on other receptors, including:
- Dopamine D4 receptors: Levophed has been shown to act as a potent agonist at the recombinant human dopamine D4 receptor, although with lower potency compared to dopamine 5.