Pharmacology of Phenylephrine

Introduction/Overview

Phenylephrine is a synthetic sympathomimetic amine that functions as a selective agonist at alpha-1 adrenergic receptors. As a direct-acting vasoconstrictor, it occupies a significant position in both outpatient and critical care therapeutic arsenals. Its clinical utility spans multiple disciplines, including anesthesiology, ophthalmology, otorhinolaryngology, and emergency medicine, primarily due to its predictable hemodynamic effects and favorable pharmacokinetic profile in certain formulations. The drug’s importance is underscored by its inclusion on the World Health Organization’s List of Essential Medicines, reflecting its critical role in managing hypotension and nasal congestion.

The pharmacological profile of phenylephrine is characterized by its pure alpha-1 adrenergic activity, which distinguishes it from other catecholamines and sympathomimetics that exhibit activity at beta-adrenergic receptors or induce indirect release of endogenous norepinephrine. This selectivity forms the basis for its therapeutic applications and its associated adverse effect profile. A comprehensive understanding of its pharmacology is essential for safe and effective clinical use, particularly given its potency and the narrow therapeutic index associated with its parenteral administration.

Learning Objectives

• Describe the molecular mechanism of action of phenylephrine as a selective alpha-1 adrenergic receptor agonist and the subsequent physiological effects on vascular smooth muscle and other tissues.
• Outline the pharmacokinetic properties of phenylephrine, including the significant differences in bioavailability and metabolism between intravenous, oral, and topical formulations.
• Identify the primary therapeutic indications for phenylephrine, distinguishing between its use as a vasopressor in anesthesia and critical care and its use as a decongestant in over-the-counter preparations.
• Analyze the major adverse effects and drug interactions associated with phenylephrine, with particular attention to hypertensive crises and reflex bradycardia.
• Apply knowledge of phenylephrine pharmacology to special populations, including patients with comorbid cardiovascular disease, pregnant individuals, and those with hepatic impairment.

Classification

Phenylephrine is systematically classified within several overlapping pharmacological and chemical hierarchies. These classifications provide a framework for understanding its therapeutic role, mechanism, and relationship to other agents.

Pharmacotherapeutic Classification

Within standard pharmacotherapeutic classification systems, phenylephrine is categorized primarily as a vasopressor agent and a nasal decongestant. In the context of anesthesia and critical care, it is a first-line agent for the treatment of hypotension, particularly when associated with a decrease in systemic vascular resistance. In otorhinolaryngology and general practice, it is classified as a topical decongestant due to its ability to constrict mucosal blood vessels in the nasal passages and sinuses.

Pharmacodynamic Classification

Based on its mechanism of action, phenylephrine is a direct-acting sympathomimetic amine. More specifically, it is a selective alpha-1 adrenergic receptor agonist. This distinguishes it from:

• Mixed-acting agonists (e.g., ephedrine), which both directly stimulate receptors and cause the release of norepinephrine from nerve terminals.
• Non-selective agonists (e.g., norepinephrine, epinephrine), which stimulate multiple adrenergic receptor subtypes (alpha-1, alpha-2, beta-1, beta-2).
• Beta-selective agonists (e.g., dobutamine, albuterol).

Its selectivity for the alpha-1 receptor subtype is relative and dose-dependent; at very high concentrations, some interaction with alpha-2 receptors may occur.

Chemical Classification

Chemically, phenylephrine is classified as a substituted phenylethylamine. Its systematic IUPAC name is (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol. It is a synthetic analogue of the endogenous catecholamines, but it lacks the catechol moiety (a benzene ring with two adjacent hydroxyl groups). This structural difference is pharmacologically significant: the absence of hydroxyl groups in the 3 and 4 positions of the benzene ring renders it resistant to metabolism by catechol-O-methyltransferase (COMT) and increases its oral bioavailability compared to catecholamines like epinephrine. However, it retains the beta-hydroxyl group, which is important for direct receptor agonist activity. Phenylephrine hydrochloride is the salt form most commonly used in pharmaceutical preparations.

Mechanism of Action

The pharmacological effects of phenylephrine are mediated almost exclusively through its action as a direct and relatively selective agonist at postsynaptic alpha-1 adrenergic receptors. This receptor interaction initiates a well-characterized intracellular signaling cascade that culminates in smooth muscle contraction, primarily in the vasculature.

Receptor Interactions and Selectivity

Phenylephrine exhibits high affinity for the alpha-1 adrenergic receptor family. Alpha-1 receptors are G-protein coupled receptors (GPCRs) predominantly located on postsynaptic membranes of effector organs. Three subtypes (alpha-1A, alpha-1B, alpha-1D) have been identified, all of which couple to the G_q/11 protein. Phenylephrine does not demonstrate clinically significant selectivity among these subtypes. Its affinity for alpha-2 and beta-adrenergic receptors is markedly lower, requiring concentrations several orders of magnitude higher to produce activation. This receptor selectivity is the cornerstone of its clinical profile, producing potent vasoconstriction without direct cardiac stimulation (beta-1 effect) or bronchodilation (beta-2 effect).

Molecular and Cellular Mechanisms

Binding of phenylephrine to the alpha-1 adrenergic receptor induces a conformational change that activates the associated heterotrimeric G_q protein. The activated G_q alpha subunit subsequently activates the membrane-bound enzyme phospholipase C-beta (PLC-β). PLC-β hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP₂) in the cell membrane, generating two key second messengers: inositol trisphosphate (IP₃) and diacylglycerol (DAG).

IP₃ diffuses into the cytosol and binds to IP₃ receptors on the sarcoplasmic reticulum (SR), triggering the release of stored intracellular calcium (Ca²⁺). The rapid increase in cytosolic Ca²⁺ concentration forms a complex with calmodulin. This calcium-calmodulin complex activates myosin light-chain kinase (MLCK), which phosphorylates the regulatory light chains of myosin. Phosphorylated myosin interacts with actin, initiating cross-bridge cycling and smooth muscle contraction.

Concurrently, DAG remains in the plasma membrane and activates protein kinase C (PKC). PKC activation contributes to sustained contraction through several mechanisms, including phosphorylation of ion channels to promote further Ca²⁺ influx (e.g., via L-type voltage-gated calcium channels) and inhibition of myosin light-chain phosphatase, which maintains the phosphorylated, active state of myosin. The net effect in vascular smooth muscle is a powerful and sustained contraction, leading to vasoconstriction.

Systemic Pharmacodynamic Effects

The primary systemic effect of phenylephrine is arteriolar vasoconstriction. This increases systemic vascular resistance (SVR) and, by extension, mean arterial pressure (MAP). The pressor response follows a predictable dose-response relationship when administered intravenously. A characteristic hemodynamic consequence is a reflex bradycardia. The abrupt increase in arterial pressure is detected by baroreceptors in the carotid sinus and aortic arch. This enhances parasympathetic (vagal) outflow and inhibits sympathetic outflow to the sinoatrial node, resulting in a decrease in heart rate. This reflex can be profound and is a dose-limiting effect in some patients.

Regional blood flow is redistributed according to the density of alpha-1 receptors in different vascular beds. Constriction is pronounced in cutaneous, mucosal, and splanchnic circulations. Renal and splanchnic blood flow may decrease significantly at higher doses. Coronary and cerebral blood flow are generally maintained due to autoregulatory mechanisms, provided the systemic pressure remains within autoregulatory limits. Phenylephrine has minimal direct effect on the heart due to its lack of beta-1 activity, although the increased afterload may increase myocardial oxygen demand.

In other organ systems, activation of alpha-1 receptors in the radial muscle of the iris (dilator pupillae) causes mydriasis (pupil dilation) without cycloplegia (paralysis of accommodation). In the nasal and ocular mucosa, vasoconstriction reduces blood flow and capillary permeability, leading to decreased edema and congestion.

Pharmacokinetics

The pharmacokinetic profile of phenylephrine is highly formulation-dependent, with significant differences observed between intravenous, oral, and topical routes of administration. These differences have direct clinical implications for dosing, onset of action, and therapeutic utility.

Absorption

Intravenous Administration: Following IV administration, phenylephrine is immediately and completely bioavailable, resulting in a rapid onset of action, typically within one minute. The peak pressor effect occurs within several minutes. This route is used when precise and immediate control of blood pressure is required, such as in anesthesia or septic shock.

Oral Administration: Oral bioavailability is notoriously low and highly variable, estimated to be as low as 38%. This is primarily due to extensive and saturable first-pass metabolism in the intestinal wall and liver by the enzyme monoamine oxidase (MAO). The low and unpredictable systemic absorption is the reason oral phenylephrine is considered to have questionable efficacy as a systemic decongestant at standard over-the-counter doses (10 mg). Higher doses increase the risk of systemic adverse effects without reliably improving efficacy.

Topical Administration (Intranasal, Ophthalmic): Absorption from mucosal surfaces is more efficient than from the gastrointestinal tract. Intranasal administration can lead to significant systemic absorption, potentially causing hypertension and other systemic alpha-agonist effects, especially with overuse. Ophthalmic administration for mydriasis can also result in systemic absorption via the nasolacrimal duct, with cases of severe hypertension reported, particularly in infants.

Intramuscular/Subcutaneous Administration: Absorption from these sites is more gradual than IV but faster than oral, with effects beginning within 10-15 minutes and lasting up to one hour. These routes are less commonly used for phenylephrine.

Distribution

Phenylephrine is a relatively small, hydrophilic molecule. Its volume of distribution (V_d) is moderate, approximately 2-3 L/kg, suggesting distribution into both the extracellular fluid and some tissues. It does not readily cross the blood-brain barrier due to its polarity, which minimizes central nervous system effects such as stimulation or anxiety that are seen with more lipophilic sympathomimetics (e.g., ephedrine). Protein binding is not considered clinically significant.

Metabolism

The primary metabolic pathway for phenylephrine is conjugation via sulfation and glucuronidation in the intestinal wall and liver. Unlike catecholamines, it is not a substrate for catechol-O-methyltransferase (COMT). A minor pathway involves oxidative deamination by monoamine oxidase (MAO), particularly in the gut during first-pass metabolism. The metabolites, primarily inactive sulfate and glucuronide conjugates, are pharmacologically inert. The extensive presystemic metabolism is the major determinant of its low oral bioavailability.

Excretion

Phenylephrine and its metabolites are eliminated predominantly by renal excretion. After intravenous administration, approximately 80-90% of a dose is recovered in the urine within 24-48 hours, with only 2-3% as unchanged drug. The remainder is excreted as conjugates. The elimination half-life (t_1/2) after IV administration is relatively short, approximately 2-3 hours. The clearance of phenylephrine is primarily dependent on hepatic conjugation and renal excretion of metabolites.

Pharmacokinetic Parameters and Dosing Considerations

The short half-life necessitates continuous intravenous infusion for sustained hemodynamic effect in critical care settings. Typical IV bolus doses range from 40-100 mcg, with infusion rates commonly starting at 0.5 mcg/kg^-1/min^-1 and titrated to effect, often up to 5-10 mcg/kg^-1/min^-1. For nasal decongestion, topical solutions of 0.25-1% are used, typically for no more than 3-5 consecutive days to avoid rebound congestion (rhinitis medicamentosa). Ophthalmic solutions are usually 2.5% or 10%. The disparity between routes underscores the principle that the pharmacokinetic profile dictates the appropriate formulation for a given therapeutic goal.

Therapeutic Uses/Clinical Applications

The clinical applications of phenylephrine are derived directly from its pharmacodynamic effect of alpha-1 mediated vasoconstriction. Its uses can be broadly divided into systemic (parenteral) and local (topical) indications.

Approved Indications

1. Treatment of Hypotension: This is the primary indication for intravenous phenylephrine.

• Anesthesia-Induced Hypotension: It is a first-line vasopressor for hypotension caused by spinal or epidural anesthesia, which induces sympathetic blockade and decreased systemic vascular resistance. Its pure alpha-agonist profile makes it ideal for this scenario, as it directly counteracts the loss of vascular tone.
• Hypotension in Septic Shock: Often used as an adjunctive vasopressor, typically after initial fluid resuscitation and initiation of a primary agent like norepinephrine. It may be selected in patients with tachyarrhythmias where avoidance of beta-agonist activity is desired.
• Drug-Induced Hypotension: Used to counteract hypotension from overdose with vasodilators or during procedures where deliberate hypotension is reversed.

2. Nasal Decongestion: As an intranasal preparation (often combined with other agents like antihistamines), phenylephrine is indicated for the temporary relief of nasal congestion due to the common cold, sinusitis, or allergic rhinitis. It acts by constricting dilated blood vessels in the nasal mucosa.

3. Ophthalmic Procedures:

• Mydriasis: Used to dilate the pupil prior to ophthalmoscopic examination, surgical procedures, or in the management of uveitis. The 2.5% concentration is often used for simple examination, while 10% is reserved for procedures.
• Vasoconstriction: As a conjunctival decongestant to relieve redness and as a adjunct to reduce bleeding during ocular surgery.
• Diagnostic Use: In Horner’s syndrome testing, phenylephrine can help localize the lesion due to denervation supersensitivity.

4. Adjunct to Local Anesthetics: Added to local anesthetic solutions (e.g., in dentistry or spinal anesthesia) to produce vasoconstriction at the site of injection. This slows the absorption of the anesthetic, prolonging its duration of action and reducing systemic toxicity.

Off-Label and Less Common Uses

Paroxysmal Supraventricular Tachycardia (PSVT): Historically, intravenous phenylephrine was used to terminate PSVT through its mechanism of inducing reflex bradycardia via a sharp increase in blood pressure. This use has been largely supplanted by safer vagal maneuvers and pharmacological agents like adenosine, but it may be considered in specific contexts where the patient is also hypotensive.

Priapism: Intracavernosal injection of phenylephrine is a standard treatment for ischemic (low-flow) priapism. Its alpha-agonist effect causes constriction of the cavernosal arteries and smooth muscle trabeculae, facilitating detumescence. This is a high-stakes procedure requiring careful hemodynamic monitoring due to the risk of systemic absorption.

Hypotension during Pheochromocytoma Resection: Following tumor removal and the consequent drop in circulating catecholamines, phenylephrine infusion may be used to support blood pressure.

Adverse Effects

The adverse effects of phenylephrine are primarily extensions of its pharmacological activity at alpha-1 adrenergic receptors. The incidence and severity are strongly correlated with the route of administration, dose, and rate of infusion.

Common Side Effects

These effects are often predictable and dose-related.

• Cardiovascular: Reflex bradycardia is the most common cardiovascular effect with IV use. Patients may also experience sensations of palpitations, tightness in the chest, or headache due to the rapid increase in blood pressure. Peripheral vasoconstriction can lead to reduced peripheral perfusion, cool extremities, and pallor.
• Local Effects (Topical): With intranasal use, transient burning, stinging, or dryness of the nasal mucosa is common. Rebound congestion (rhinitis medicamentosa) occurs with prolonged use (>5 days) due to down-regulation of alpha receptors and reactive hyperemia upon discontinuation. Ophthalmic use can cause transient stinging, blurred vision, and photophobia.
• Central Nervous System: Anxiety, restlessness, dizziness, and headache may occur, particularly if a rapid or excessive pressor response leads to acute hypertension.

Serious and Rare Adverse Reactions

Hypertensive Crisis: This is the most serious acute adverse reaction, potentially leading to intracranial hemorrhage, aortic dissection, or acute heart failure. Risk is highest with rapid IV bolus administration, accidental overdose, or in patients with pre-existing hypertension or pheochromocytoma. Ophthalmic administration in infants has caused severe hypertension and stroke.

Severe Bradycardia and Heart Block: The baroreceptor-mediated reflex can be excessive, leading to profound sinus bradycardia or even asystole in susceptible individuals, particularly those with underlying sinus node disease or those receiving concomitant negative chronotropic drugs.

Extravasation Injury: Infiltration of IV phenylephrine into surrounding tissue can cause severe local vasoconstriction, leading to tissue ischemia, necrosis, and sloughing. Prompt local infiltration with an alpha-antagonist (e.g., phentolamine) is the standard treatment.

Acute Pulmonary Edema: The sudden increase in afterload can precipitate left ventricular failure in patients with compromised cardiac function.

Reduced Organ Perfusion: Excessive vasoconstriction can compromise blood flow to vital organs, including the kidneys (acute kidney injury), intestines (mesenteric ischemia), and extremities (digital ischemia).

Allergic Reactions: Urticaria, contact dermatitis (with topical use), and anaphylactoid reactions are rare but have been reported.

Black Box Warnings and Contraindications

Phenylephrine does not carry a formal FDA Black Box Warning. However, its contraindications are strict and based on the potential for catastrophic outcomes. Absolute contraindications include severe hypertension, ventricular tachycardia, and known hypersensitivity. It is also contraindicated in patients with severe coronary artery disease or peripheral vascular disease (e.g., Raynaud’s phenomenon, thromboangiitis obliterans) due to the risk of ischemia. Its use in patients with pheochromocytoma is contraindicated as it may provoke a hypertensive crisis.

Drug Interactions

Phenylephrine interacts with numerous drug classes, primarily through pharmacodynamic synergism or antagonism at the adrenergic receptor. Knowledge of these interactions is critical to avoid therapeutic failure or toxicity.

Major Pharmacodynamic Interactions

Synergistic Pressor Effects (Increased Risk of Hypertension):

• Monoamine Oxidase Inhibitors (MAOIs): This is a classic and potentially lethal interaction. MAOIs (e.g., phenelzine, tranylcypromine) inhibit the primary intestinal and hepatic metabolic pathway for orally administered phenylephrine. This can lead to a dramatic, prolonged increase in systemic phenylephrine levels, resulting in severe hypertensive crisis, intracranial hemorrhage, and death. A washout period of at least 2 weeks is required after discontinuing an MAOI before phenylephrine can be safely administered.
• Other Sympathomimetic Agents: Concurrent use with drugs like epinephrine, norepinephrine, dopamine, ephedrine, or pseudoephedrine can lead to additive alpha-agonist effects, increasing the risk of hypertension and arrhythmias.
• Tricyclic Antidepressants (TCAs) and Cocaine: These agents inhibit neuronal reuptake of norepinephrine (uptake-1 inhibition). When combined with a direct alpha-agonist like phenylephrine, the effect on vascular tone is potentiated, leading to exaggerated pressor responses.
• Ergot Alkaloids (e.g., ergotamine, methylergonovine): These agents are potent vasoconstrictors. Concomitant use with phenylephrine may result in extreme hypertension and peripheral ischemia.

Antagonistic Interactions (Decreased Pressor Effect):

• Alpha-Adrenergic Receptor Antagonists: Drugs such as prazosin, terazosin, doxazosin, and phenoxybenzamine competitively block the alpha-1 receptor, directly antagonizing the effects of phenylephrine. This can lead to therapeutic failure when phenylephrine is used as a vasopressor.
• Beta-Blockers (non-selective): While beta-blockers do not block alpha receptors, they can potentiate the pressor effect of phenylephrine by blocking beta-2 mediated vasodilation, leaving unopposed alpha-mediated constriction. More importantly, they can exacerbate the reflex bradycardia caused by phenylephrine, potentially leading to severe bradycardia or heart block.

Other Significant Interactions

Oxytocic Drugs: Phenylephrine may enhance the vasoconstrictive effects of oxytocin or other uterotonics, potentially leading to severe postpartum hypertension.

General Anesthetics: Volatile anesthetics (e.g., halothane, isoflurane) sensitize the myocardium to catecholamines, increasing the risk of arrhythmias. While phenylephrine has minimal direct cardiac effect, the interaction is still considered, especially with rapid blood pressure changes.

Atropine and Other Anticholinergics: These agents can block the reflex bradycardia induced by phenylephrine, potentially unmasking a tachycardia if there is any underlying beta-agonist activity or if very high doses are used.

Special Considerations

The use of phenylephrine requires careful adjustment and monitoring in specific patient populations due to altered pharmacokinetics, pharmacodynamics, or increased risk of adverse events.

Pregnancy and Lactation

Pregnancy (Category C): Animal reproduction studies have not been conducted, and there are no adequate and well-controlled studies in pregnant women. Phenylephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. As a vasoconstrictor, it has the potential to reduce uterine blood flow, which could adversely affect the fetus. However, it is frequently used in obstetric anesthesia (e.g., for spinal hypotension during cesarean delivery) where it is considered a preferred agent due to its minimal placental transfer and efficacy in maintaining maternal blood pressure and, by extension, uteroplacental perfusion. Dosing should be the lowest effective for the shortest duration.

Lactation: It is not known whether phenylephrine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sympathomimetic amines, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. The low oral bioavailability in infants suggests that the amount ingested via breast milk would likely be subtherapeutic, but caution is advised.

Pediatric and Geriatric Considerations

Pediatric Population: Safety and effectiveness for intravenous use in children are not well established and it should be used with extreme caution. For intranasal or ophthalmic use, lower concentrations are often recommended. Ophthalmic phenylephrine 10% is contraindicated in infants and used with great caution in young children due to the high risk of significant systemic absorption leading to hypertension, arrhythmias, and CNS disturbances. Dosing must be carefully calculated based on weight for any systemic use.

Geriatric Population: Older patients may be more sensitive to the effects of phenylephrine. Age-related increases in vascular stiffness and baroreceptor reflex impairment can lead to exaggerated and prolonged pressor responses. The reflex bradycardia may be more pronounced or less predictable. Furthermore, the presence of comorbid conditions such as hypertension, atherosclerosis, and renal impairment is common. A lower initial dose and careful titration are imperative. The use of oral phenylephrine as a decongestant is generally discouraged in the elderly due to the risk of precipitating hypertension, urinary retention (in men with prostatic hyperplasia), and exacerbating coronary artery disease.

Renal and Hepatic Impairment

Renal Impairment: Since phenylephrine is extensively metabolized and the metabolites are renally excreted, significant renal impairment could theoretically lead to metabolite accumulation. However, these metabolites are inactive, so dose adjustment for renal impairment is not typically required for short-term IV use. Caution is warranted due to the increased risk of fluid and electrolyte disturbances in renal patients and the potential for phenylephrine to further reduce renal blood flow.

Hepatic Impairment: The liver is the primary site for the conjugation of phenylephrine. Severe hepatic impairment (e.g., cirrhosis) could reduce the metabolic clearance of phenylephrine, potentially prolonging its half-life and intensifying its effects. This is particularly relevant for orally administered drug, where first-pass metabolism is already a major factor. In patients with severe liver disease, intravenous phenylephrine should be initiated at a lower dose and titrated cautiously with close hemodynamic monitoring.

Patients with Cardiovascular Disease

Phenylephrine must be used with extreme caution, if at all, in patients with severe coronary artery disease, congestive heart failure, tachyarrhythmias, or occlusive vascular disease. The increase in systemic vascular resistance and afterload increases myocardial oxygen demand, which can precipitate angina or myocardial infarction in patients with fixed coronary lesions. The reduction in heart rate from reflex bradycardia may be detrimental in patients dependent on heart rate for cardiac output (e.g., some forms of heart failure).

Summary/Key Points

Phenylephrine is a cornerstone agent in clinical practice whose utility is defined by its selective alpha-1 adrenergic agonist activity.

Summary of Core Principles

• Phenylephrine is a direct-acting, selective alpha-1 adrenergic receptor agonist. Its effects are mediated via the G_q-PLC-IP₃-DAG pathway, leading to vascular smooth muscle contraction and vasoconstriction.
• Pharmacokinetics are route-dependent: intravenous administration provides immediate, titratable effects; oral bioavailability is low and unreliable due to extensive first-pass metabolism; topical administration can lead to significant systemic absorption.
• The primary therapeutic applications are as an intravenous vasopressor for hypotension (especially anesthesia-induced) and as a topical agent for nasal decongestion and ocular mydriasis.
• The adverse effect profile is an extension of its pharmacology, including hypertension, reflex bradycardia, and reduced organ perfusion. Extravasation can cause tissue necrosis.
• Critical drug interactions exist, most notably with MAOIs, which can precipitate a fatal hypertensive crisis, and with alpha-blockers, which can antagonize its effect.
• Special caution is required in geriatric patients, those with cardiovascular disease, and with the use of ophthalmic preparations in infants.

Clinical Pearls

• When using IV phenylephrine for hypotension, always be prepared for the predictable reflex bradycardia. Have atropine accessible.
• For the treatment of extravasation, phentolamine (an alpha-antagonist) should be infiltrated into the ischemic area as soon as possible.
• Educate patients using OTC nasal phenylephrine to limit use to 3-5 days to avoid rebound congestion (rhinitis medicamentosa).
• In the operating room, phenylephrine is often preferred over mixed agonists like ephedrine for treating spinal hypotension due to its more predictable effect on vascular tone without direct fetal metabolic effects.
• Always verify that a patient is not taking an MAOI before administering any formulation of phenylephrine, including over-the-counter cold remedies.
• The hemodynamic goal with phenylephrine infusion is typically to achieve a target mean arterial pressure, not to normalize a high systolic pressure in isolation, as excessive vasoconstriction can compromise organ perfusion.

References

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