Phenylephrine - Drug Monograph

Introduction

Phenylephrine is a selective α₁-adrenergic receptor agonist commonly used as a decongestant and vasopressor agent. First introduced in the 1930s, it remains a widely available medication in both prescription and over-the-counter formulations. Phenylephrine is structurally similar to endogenous catecholamines but differs significantly in its pharmacological profile, exhibiting primarily peripheral vasoconstrictive effects with minimal cardiac stimulation.

Mechanism of Action

Phenylephrine exerts its therapeutic effects through selective stimulation of α₁-adrenergic receptors. This activation leads to:

• Vasoconstriction of arterioles and veins in the nasal mucosa (decongestant effect)
• Systemic vasoconstriction resulting in increased vascular resistance and blood pressure (vasopressor effect)
• Pupillary dilation via contraction of the iris dilator muscle (mydriatic effect)

Unlike epinephrine or norepinephrine, phenylephrine has minimal β-adrenergic activity, resulting in predominantly peripheral rather than cardiac effects.

Indications

• Nasal congestion (topical formulation)
• Hypotension during anesthesia (parenteral formulation)
• Vasoconstriction in regional analgesia
• Mydriasis for ophthalmologic procedures

• Paroxysmal supraventricular tachycardia
• Priapism treatment
• Hemorrhoid relief (topical formulations)

Dosage and Administration

• Adults: 1-2 sprays (0.25-0.5%) per nostril every 4 hours as needed
• Children 6-12 years: 1-2 sprays (0.25%) per nostril every 4 hours
• Maximum duration: 3 days continuous use

• IV bolus: 40-100 mcg every 1-2 minutes as needed
• IV infusion: Initial 10-20 mcg/min, titrate to effect (usual range 0.5-9 mcg/kg/min)

• Hepatic impairment: Use with caution; consider reduced dosing
• Renal impairment: No dosage adjustment typically needed
• Geriatric patients: Start with lower doses due to increased sensitivity

Pharmacokinetics

• Oral: Extensive first-pass metabolism (low bioavailability ~38%)
• Nasal: Rapid local absorption with minimal systemic exposure
• IV: Immediate and complete bioavailability

• Volume of distribution: ~210 L
• Protein binding: Approximately 95%

• Primarily metabolized in liver via monoamine oxidase (MAO) and sulfotransferase enzymes
• Extensive presystemic metabolism following oral administration

• Half-life: 2-3 hours
• Excretion: Primarily renal (80%) as metabolites

Contraindications

• Hypersensitivity to phenylephrine or any component of formulation
• Severe hypertension
• Ventricular tachycardia
• Concomitant use with MAO inhibitors or within 14 days of discontinuation
• Narrow-angle glaucoma
• Severe coronary artery disease

Warnings and Precautions

• Risk of severe hypertension, particularly in patients with autonomic dysfunction
• May cause bradycardia through vagal reflex
• Use with extreme caution in patients with hyperthyroidism, diabetes, or cardiovascular disease
• Rebound congestion with prolonged nasal use (>3-5 days)
• Tissue necrosis and sloughing with extravasation of IV formulation
• Not recommended during pregnancy (Category C) unless clearly needed

Drug Interactions

• MAO inhibitors: Risk of hypertensive crisis
• Tricyclic antidepressants: Potentiated pressor effects
• β-blockers: Unopposed α-adression may cause severe hypertension
• Oxytocic drugs: Enhanced pressor effects
• Ergot alkaloids: Increased vasoconstrictive effects

• Guanethidine: Enhanced pressor response
• Reserpine: Reduced phenylephrine effectiveness
• Digitalis glycosides: Increased risk of cardiac arrhythmias

Adverse Effects

• Headache
• Reflex bradycardia
• Hypertension
• Nasal burning or stinging (topical)
• Anxiety
• Palpitations

• Severe hypertension
• Ventricular arrhythmias
• Myocardial ischemia
• Cerebral hemorrhage
• Tissue necrosis with extravasation
• Angioedema or anaphylaxis

Monitoring Parameters

• Continuous blood pressure monitoring
• Heart rate and rhythm monitoring
• Peripheral perfusion assessment
• Urine output
• Electrocardiogram for patients with cardiac risk factors

• Blood pressure in hypertensive patients
• Symptoms of rebound congestion
• Signs of systemic absorption

Patient Education

• Use nasal spray for maximum 3 consecutive days to prevent rebound congestion
• Report chest pain, severe headache, or palpitations immediately
• Inform all healthcare providers about phenylephrine use
• Avoid concurrent use with other decongestants or stimulants
• Do not use if you have high blood pressure, heart disease, or thyroid problems without medical supervision
• Shake nasal spray well before use
• Proper administration technique: Lean head slightly forward, spray away from nasal septum

References

1. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. McGraw Hill; 2018. 2. Phenylephrine hydrochloride [package insert]. Lake Forest, IL: Hospira, Inc; 2019. 3. Smith BP, Ferguson KL. Phenylephrine: mechanisms and clinical use. J Infus Nurs. 2018;41(2):98-105. 4. FDA Drug Safety Communication: Serious adverse events from accidental ingestion of eye drops. US Food and Drug Administration; 2020. 5. Johnson PN, Miller JL, Hagemann TM. Parenteral phenylephrine: use in the critical care setting. J Pediatr Pharmacol Ther. 2019;24(4):276-289. 6. Clinical Pharmacology [Internet]. Tampa: Elsevier; 2023. Phenylephrine; [cited 2023 Nov 15]. Available from: clinicalkey.com