Usage
- Phenoxybenzamine is prescribed for the control of hypertension episodes associated with pheochromocytoma. It is also sometimes used off-label for micturition disorders.
- Pharmacological classification: Alpha-adrenergic blocking agent (specifically, a non-selective, non-competitive alpha-blocker).
- Mechanism of Action: Phenoxybenzamine irreversibly binds to alpha-adrenergic receptors, preventing catecholamines (like norepinephrine and epinephrine) from binding and exerting their vasoconstricting effects. This leads to vasodilation and a decrease in blood pressure.
Alternate Names
How It Works
- Pharmacodynamics: Phenoxybenzamine primarily blocks alpha-1 adrenergic receptors, leading to peripheral vasodilation and a decrease in blood pressure. It also blocks alpha-2 receptors, which can increase norepinephrine release, leading to reflex tachycardia.
- Pharmacokinetics: Administered orally. Phenoxybenzamine is well-absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism, resulting in lower bioavailability. It is highly lipophilic and distributes widely throughout the body. Metabolism is complex, and elimination is primarily via renal and biliary routes.
- Mode of Action: Irreversible binding to alpha-adrenergic receptors.
- Receptor Binding: Non-selective and non-competitive antagonist of alpha-1 and alpha-2 adrenergic receptors.
- Elimination Pathways: Renal and biliary excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Initial dose: 10 mg orally once or twice daily.
- Maintenance dose: The dose should be increased by 10 mg daily until blood pressure control is achieved or postural hypotension becomes troublesome. The usual maintenance dose is 20-40 mg orally 2-3 times per day. Doses as high as 240 mg daily have been reported. The optimal dose is determined by blood pressure response.
Children:
- Initial Dose: 0.2 mg/kg/dose orally once daily.
- Maintenance Dose: The dose can be slowly increased by 0.2 mg/kg daily to a maximum of 1.2 mg/kg/day divided three to four times a day.
- Pediatric safety considerations: Experience in pediatric patients is limited. Use with caution.
Special Cases:
- Elderly Patients: Start with a lower dose (10 mg daily) and titrate cautiously due to increased sensitivity to side effects.
- Patients with Renal Impairment: Use with caution; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be necessary.
- Patients with Comorbid Conditions: Use cautiously in patients with cerebrovascular or cardiovascular disease.
Clinical Use Cases
Phenoxybenzamine’s primary clinical use is the preoperative management of pheochromocytoma. Dosage is titrated to control blood pressure and minimize perioperative complications.
Dosage Adjustments
Dose adjustments are made based on individual patient response and tolerance. Monitor blood pressure and heart rate closely when adjusting doses.
Side Effects
Common Side Effects
- Nasal congestion
- Orthostatic hypotension
- Dizziness
- Drowsiness/Fatigue
- Miosis (constricted pupils)
- Reflex tachycardia
- Inhibited ejaculation/Retrograde ejaculation
- Gastrointestinal irritation
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis)
- Syncope (fainting)
- Severe hypotension
Long-Term Effects
- Potential for carcinogenic effects with long-term use; thus, long-term use is not recommended.
Adverse Drug Reactions (ADR)
- Severe hypotension, orthostatic hypotension, and reflex tachycardia require immediate intervention.
Contraindications
- Hypersensitivity to phenoxybenzamine.
- Conditions where a fall in blood pressure is undesirable (e.g., cerebrovascular accident, myocardial infarction recovery period, severe coronary artery disease).
Drug Interactions
- Drugs that stimulate alpha and beta-adrenergic receptors (can exacerbate hypotension and tachycardia).
- Blood pressure medications (additive hypotensive effects).
- CYP450 interactions: While phenoxybenzamine’s metabolism is complex, it doesn’t have strong CYP450 interactions.
- OTC drugs and supplements: Interactions with OTC medications are not extensively studied.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Phenoxybenzamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Fetal risks: Potential teratogenic effects.
- Drug excretion in breast milk: Unknown. Avoid breastfeeding while on Phenoxybenzamine.
Drug Profile Summary
- Mechanism of Action: Irreversible alpha-adrenergic receptor blockade.
- Side Effects: Orthostatic hypotension, reflex tachycardia, nasal congestion, dizziness, miosis, inhibited ejaculation.
- Contraindications: Hypersensitivity, conditions where hypotension is hazardous.
- Drug Interactions: Alpha/beta agonists, antihypertensives.
- Pregnancy & Breastfeeding: Category C; use with caution if benefits outweigh risks. Not recommended while breastfeeding.
- Dosage: Adults: Start 10mg BID, increase to 20-40mg TID. Children: 0.2-1.2 mg/kg/day in 3-4 divided doses.
- Monitoring Parameters: Blood pressure, heart rate.
Popular Combinations
Beta-blockers are sometimes used in conjunction with phenoxybenzamine, particularly when managing tachycardia associated with pheochromocytoma.
Precautions
- Monitor blood pressure and heart rate carefully, especially during dose titration.
- Educate patients about the risk of orthostatic hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Phenoxybenzamine?
A: Adults: Initial dose 10 mg orally 1-2 times/day, titrate up to 20-40 mg 2-3 times/day. Children: 0.2-1.2 mg/kg/day divided TID-QID. Elderly: initiate at 10 mg/day and titrate cautiously.
Q2: What is the primary use of Phenoxybenzamine?
A: Management of hypertension associated with pheochromocytoma.
Q3: What are the common side effects of Phenoxybenzamine?
A: Nasal congestion, orthostatic hypotension, dizziness, reflex tachycardia, miosis, and inhibited ejaculation.
Q4: What are the contraindications for Phenoxybenzamine?
A: Hypersensitivity, conditions where a fall in blood pressure is undesirable.
Q5: How does Phenoxybenzamine work?
A: It irreversibly blocks alpha-adrenergic receptors.
Q6: Can Phenoxybenzamine be used during pregnancy?
A: Category C. Use only if potential benefit outweighs risks. Consult with obstetrician.
Q7: Is Phenoxybenzamine safe to use while breastfeeding?
A: Not recommended as its presence in breast milk is unknown. Potential risks to infant.
Q8: What should be monitored during Phenoxybenzamine therapy?
A: Blood pressure and heart rate.
Q9: What are the potential drug interactions with Phenoxybenzamine?
A: Interactions can occur with drugs that stimulate both alpha and beta receptors, as well as antihypertensive medications.
Q10: Can Phenoxybenzamine be used long-term?
A: No. Long-term use is not recommended due to a potential increased risk of carcinogenicity.
