levarterenol

Action and Spectrum

Actions and Spectrum: 

levarterenol, also known as norepinephrine, is a medication with a well-defined action and a spectrum of effects primarily related to its role as a sympathomimetic agent. It primarily acts on adrenergic receptors in the sympathetic nervous system.  

Vasoconstriction: levarterenol stimulates alpha-1 adrenergic receptors found in the smooth muscle of blood vessels. Activation of these receptors leads to vasoconstriction, causing a narrowing of blood vessels throughout the body. This vasoconstrictive action makes levarterenol highly effective in raising blood pressure, making it a valuable medication in treating conditions like shock (including septic and hypovolemic shock) and severe hypotension. 

Cardiac Stimulation: Besides its vasoconstrictive properties, levarterenol stimulates beta-1 adrenergic receptors in the myocardium (heart muscle). Activation of these receptors increases the heart rate (positive chronotropic effect) and enhances the force of each heartbeat (positive inotropic effect). As a result, levarterenol improves cardiac output by enhancing the volume of blood ejected from the heart with each beat. This helps improve tissue perfusion and oxygen delivery, particularly in cases with reduced cardiac output, such as bradycardia or cardiac-related shock. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: levarterenol should not be administered to individuals with a known hypersensitivity or allergy to the drug or its components. Allergic reactions can be severe and life-threatening. 
• Occlusive Vascular Diseases: levarterenol should be used cautiously or avoided in patients with preexisting occlusive vascular diseases, such as peripheral vascular disease, as it can worsen ischemia in affected tissues. 
• Ventricular Tachycardia: It is contraindicated in patients with ventricular tachycardia, a potentially life-threatening arrhythmia, as levarterenol can exacerbate the arrhythmia and increase the risk of cardiac arrest. 
• Hypovolemia without Adequate Fluid Replacement: levarterenol should not be used as a first-line treatment in patients with hypovolemia (low blood volume) without adequate fluid replacement. Addressing hypovolemia with appropriate fluids is generally a priority before using vasoactive medications like levarterenol. 
• Phaeochromocytoma: levarterenol is contraindicated in patients with phaeochromocytoma, a rare adrenal gland tumor that can release excessive amounts of catecholamines. Using levarterenol in such patients can lead to severe hypertensive crises. 
• Coronary Artery Insufficiency: Caution should be exercised when administering levarterenol to patients with underlying coronary artery insufficiency or ischemic heart disease, as it can increase myocardial oxygen demand and potentially worsen ischemia. 
• Use with Monoamine Oxidase Inhibitors (MAOIs): levarterenol should not be used concomitantly with the monoamine oxidase inhibitors or within 14 days of discontinuing MAOIs, as it can result in a hypertensive crisis due to the interaction between these drugs. 
• Closed-Angle Glaucoma: levarterenol may exacerbate closed-angle glaucoma, characterized by increased intraocular pressure. It should be used cautiously, if at all, in patients with this condition. 
• Preexisting Severe Hypertension: In patients with preexisting severe hypertension, levarterenol should be used cautiously and with close monitoring to avoid excessive increases in blood pressure. 
• Pregnancy and Lactation: The use of levarterenol during pregnancy and lactation should be carefully considered, as there may be potential risks to the fetus or nursing infant. The decision to use the medication in these situations should be made in consultation with a healthcare provider. 

Caution 

• Dose Titration: levarterenol should be cautiously administered, and the dosage should be titrated carefully to achieve the desired therapeutic effect while typically minimizing side effects. Individual patient responses can vary, so starting with the lowest effective dose is advisable. 
• Continuous Monitoring: Patients receiving levarterenol should be continuously monitored, including vital signs (blood pressure, heart rate, respiratory rate, and oxygen saturation). Frequent assessments are essential to adjust the dosage and assess the patient’s response. 
• Extravasation Risk: levarterenol is a potent vasoconstrictor, and if it leaks from the intravenous (IV) line into the surrounding tissues (extravasation), it can cause tissue necrosis. Proper IV placement and regular site assessment are crucial to prevent this complication. 
• Cardiac Arrhythmias: levarterenol can cause or exacerbate cardiac arrhythmias, especially in patients with preexisting or cardiac conditions. Patients with known arrhythmias should be closely monitored, and caution should be exercised when using levarterenol in this population. 
• Hypertensive Response: levarterenol administration can lead to a significant increase in blood pressure. Care should be taken to avoid excessively high blood pressure levels, which may lead to complications. The goal is to raise blood pressure appropriately without causing harm. 
• Ischemic Heart Disease: Patients with underlying coronary artery disease or ischemic heart disease may be at increased risk of myocardial ischemia or angina when receiving levarterenol. Careful monitoring and consideration of alternative treatments may be necessary in these cases. 
• Peripheral Vascular Disease: Individuals with the peripheral vascular disease may experience worsening of ischemia or reduced blood flow to extremities when receiving levarterenol. Caution is needed in these patients, and alternative treatments should be considered. 
• Renal Impairment: levarterenol can affect renal blood flow and may worsen renal function in patients with preexisting renal impairment.  
• Pediatric and Geriatric Populations: Special caution should be exercised when using levarterenol in pediatric and geriatric populations, as they may have different physiological responses and tolerances to the medication. Dosing and monitoring should be tailored to the patient’s age and condition. 
• Drug Interactions: levarterenol may interact with other medications, especially those affecting the sympathetic nervous system. Healthcare providers should know potential drug interactions and adjust treatment plans accordingly. 
• Duration of Use: levarterenol is typically used for short-term treatment of acute conditions. Prolonged use should be avoided, and the medication should be tapered or discontinued as soon as the patient’s condition allows. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

levarterenol, a sympathomimetic agent, exerts its pharmacological effects primarily by stimulating alpha-1 adrenergic receptors, leading to vasoconstriction of peripheral blood vessels, which increases systemic vascular resistance and raises blood pressure.

Additionally, it stimulates beta-1 adrenergic receptors in the heart, resulting in increased heart rate and improved cardiac contractility, ultimately enhancing cardiac output. This dual action makes levarterenol effective in treating shock, severe hypotension, and bradycardia by restoring blood pressure and tissue perfusion.  

Pharmacodynamics: 

Mechanism of action: Its mechanism involves interacting with adrenergic receptors in the body, particularly alpha-1 adrenergic receptors and, to a lesser extent, beta-1 adrenergic receptors.  

Stimulation of Alpha-1 Adrenergic Receptors: 

levarterenol binds to and activates alpha-1 adrenergic receptors found on smooth muscle cells in various tissues, including blood vessels. 

Activation of alpha-1 receptors leads to vasoconstriction, which results in the narrowing of blood vessels. This vasoconstrictive effect increases systemic vascular resistance, causing an elevation in blood pressure. 

Stimulation of Beta-1 Adrenergic Receptors: 

levarterenol also stimulates beta-1 adrenergic receptors in the heart’s myocardium (muscle). 

Activation of beta-1 receptors in the heart leads to two main effects: 

Increased heart rate (positive chronotropic effect): levarterenol increases the heart’s contraction rate, resulting in a faster heart rate. 

Increased contractility (positive inotropic effect): levarterenol enhances the force of each heartbeat, leading to increased cardiac output. 

Pharmacokinetics: 

Absorption:  

levarterenol is usually administered intravenously (IV) in clinical settings. The medication enters the bloodstream intravenously, ensuring rapid and reliable absorption. Oral administration of levarterenol is not shared and is generally ineffective because it undergoes significant first-pass metabolism in the liver, which reduces its bioavailability. 

Distribution:  

Once in the bloodstream, levarterenol circulates throughout the body. It acts on alpha-1 adrenergic receptors in vascular smooth muscle, leading to vasoconstriction and increased systemic vascular resistance. It also stimulates beta-1 adrenergic receptors in the heart, which enhances cardiac output. levarterenol does not readily cross the blood-brain barrier, limiting its central nervous system effects. 

Metabolism:  

levarterenol undergoes extensive metabolism in the body, primarily in the liver, through enzymatic processes. The enzymes involved in its metabolism include monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). These enzymes break down levarterenol into various metabolites, then excreted from the body. The metabolism of levarterenol can vary among individuals and may be influenced by genetics and concurrent medications. 

Elimination and Excretion: 

The metabolites of levarterenol, along with any unmetabolized drug, are primarily excreted through the kidneys via urine. The exact clearance rate can vary among individuals based on factors such as renal function and renal disease. The half-life of levarterenol in the body is relatively short, typically in the range of a few minutes. 

Adminstartion

Administration: 

Trained healthcare professionals should administer levarterenol (Levophed) in a clinical setting, as it is a potent medication that can significantly affect the cardiovascular system.  

Route of Administration: levarterenol is typically administered intravenously (IV). Other routes rarely give it, and the IV route allows for rapid onset and control over the dosage. 

Dilution: levarterenol is usually supplied in vials or ampules as a concentrated solution. Before administration, it must be diluted with an appropriate IV fluid, such as normal saline (0.9% sodium chloride) or 5% dextrose in water. The dilution and concentration depend on the patient’s condition and the desired dosage. 

Infusion Pump: levarterenol is typically administered via an IV infusion pump to ensure accurate and controlled delivery. The pump allows for precise adjustment of the infusion rate based on the patient’s response. 

Initial Dosage: The initial dosage of levarterenol will vary depending on the patient’s clinical condition, blood pressure, and heart rate. It is usually started at a low dose and titrated upward based on the patient’s response. 

Continuous Monitoring: Patients receiving levarterenol should be closely monitored. Vital signs, including BP, heart rate, respiratory rate, and also oxygen saturation, should be monitored continuously. Frequent assessments are essential to adjust the dosage and assess the patient’s response. 

Titration: levarterenol administration aims to raise blood pressure to an appropriate level without causing harm. The dosage should be titrated to achieve the desired therapeutic effect while minimizing adverse effects. Frequent adjustments may be necessary. 

Extravasation Prevention: To prevent the risk of extravasation (leakage of the medication into surrounding tissues), proper IV site placement and regular assessment of the IV site are crucial. If extravasation occurs, it should be promptly recognized and managed. 

Duration of Use: levarterenol is typically used for short-term treatment of acute conditions, such as shock or severe hypotension. Prolonged use should be avoided, and the medication should be tapered or discontinued as soon as the patient’s condition allows. 

Patient-Specific Considerations: The decision to use levarterenol and the dosage should be based on a thorough assessment of the patient’s clinical condition, including age, comorbidities, and underlying medical conditions. Special consideration should be given to pediatric and geriatric populations. 

Drug Interactions: Healthcare providers should be aware of potential drug interactions when administering levarterenol, especially medications affecting the sympathetic nervous system. Adjustments to treatment plans may be necessary. 

Documentation: Accurate documentation of the medication administration, including the dosage, infusion rate, and the patient’s response, is essential for medical records. 

Discontinuation: levarterenol should be tapered or discontinued gradually to avoid abrupt changes in blood pressure and potential rebound hypotension when the patient’s condition improves. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: levarterenol 

Why do we use levarterenol? 

levarterenol is a medication with several medical uses, primarily related to raising blood pressure and improving cardiac output. It is classified as a sympathomimetic or adrenergic agonist and primarily acts on alpha-1 adrenergic receptors.  

Treatment of Shock: levarterenol is commonly used in the management of various types of shock, including: 

Septic Shock: In septic shock caused by severe infections, levarterenol helps raise blood pressure and counteract vasodilation, a characteristic feature of septic shock. 

Hypovolemic Shock: In cases of hypovolemic shock due to significant blood loss (e.g., trauma, surgery), levarterenol can increase blood pressure and improve tissue perfusion. 

Cardiogenic Shock: levarterenol may be used with other medications to support blood pressure and cardiac output in cardiogenic shock resulting from heart failure. 

Hypotension: levarterenol treats severe hypotension (low blood pressure) that may occur due to various causes, including anesthesia, certain medications, or medical conditions. 

Vasodilatory Shock: levarterenol can be used in vasodilatory shock states, such as distributive shock, where excessive dilation of blood vessels leads to a drop in blood pressure. It helps restore vascular tone. 

Bradycardia: In cases of severe bradycardia (slow heart rate), levarterenol can increase heart rate (chronotropic effect) and improve cardiac output. 

Congestive Heart Failure: In some cases of congestive heart failure, levarterenol may be used temporarily to support cardiac function and maintain blood pressure. 

Anesthesia-Related Hypotension: levarterenol is sometimes used during surgery to counteract anesthesia-induced hypotension.