phenoxybenzamine

Action and Spectrum

Phenoxybenzamine is a non-selective alpha-adrenergic receptor antagonist. It blocks alpha-1 and alpha-2 receptors in the body. It binds to these receptors irreversibly and prevents the action of norepinephrine. It is neurotransmitter which activates these receptors and leads to the constriction of blood vessels and other effects.

It causes blood vessels to dilate by blocking these receptors. It leads to reduces the blood pressure. Other effects like reducing the tome of smooth
muscles in the urinary tract, preventing the spasm of blood vessels in the fingers and toes in Raynaud’s disease, and reducing the sweating and tremors which is caused by excess adrenaline in pheochromocytoma.

The spectrum of phenoxybenzamine is narrow. It is used to treat hypertension which is caused by pheochromocytoma. It is a rare tumor which produces adrenaline and other hormones. It is used to manage the symptoms which are linked with Raynaud’s disease.

Drug Interaction

Adverse Reaction

Frequency not defined

Drowsiness

Dry mouth

Inhibition of ejaculation

Miosis

Sedation

Orthostatic hypotension

Tachycardia

Vomiting

Dizziness

Nasal congestion

Fatigue

Malaise

Nausea

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Hypersensitivity: Phenoxybenzamine must not be used in patients who have hypersensitivity or allergy to the drug or any of substances which is used in this drug.

Coronary artery disease: Phenoxybenzamine must be used with precaution in patients who have coronary artery disease. It can lead to reflex tachycardia and worsen the myocardial ischemia. r

Peptic ulcer disease: Phenoxybenzamine can elevate the secretion of stomach acid. It can worsen the peptic ulcer disease.

Hypotension: Phenoxybenzamine can reduce the blood pressure. It must not be used in patients who have severe hypotension.

Liver disease: Phenoxybenzamine is mainly metabolized by the liver. Caution must be taken in patients who have liver disease or impaired liver function.

Pregnancy and breastfeeding: There is a limited information is available about the safety of this drug in pregnancy and breastfeeding. It must be only used if there are some potential benefits to fetus or infant.

Caution
Cardiovascular disease: Phenoxybenzamine can lead to reflex tachycardia. It is rapid heart rate which can get worse in cardiovascular disease. Caution must be taken in patients who have heart disease or arrhythmias.

Renal impairment: Phenoxybenzamine is mainly excreted in the kidneys. Caution must be taken in patients wo have renal disease.

Hepatic impairment: Phenoxybenzamine is mainly metabolized in the liver. Caution must be taken in patients who have hepatic impairment or liver disease.

Diabetes: Phenoxybenzamine can mask some symptoms of hypoglycemia in patients who have diabetes and make it difficult to monitor the practice and control the levels of blood sugar.

Surgery: Phenoxybenzamine can lead to hypertension and cardiovascular effects which can complicate the surgery. Caution must be taken in patients who is going for surgery or anesthesia.

Interactions with other medications:
Phenoxybenzamine can interact with other medications like alpha blockers. It increases the risk of hypertension and other adverse effects. Caution must be taken in patients who are taking other medication which can reduces the blood pressure and affect the cardiovascular function.

Pregnancy / Lactation

Pregnancy consideration:

US FDA pregnancy category: C

Lactation:  

Excreted into human milk is Not known.

Pregnancy category:

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/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 available 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

Phenoxybenzamine is an alpha-adrenergic receptor antagonist. It blocks the catecholamines like epinephrine and norepinephrine. There hormones bind to alpha receptors in the body. It causes relaxation of the smooth muscles in the blood vessels and other organs by blocking these receptors. This can lead to vasodilation and reduced blood pressure.

It has a long duration of action. It lasts for many hours after a single dose. It is irreversible. It binds to alpha receptors and cannot easily replaced by other medications.

Pharmacodynamics:

Phenoxybenzamine is a non-selective alpha blocker. It blocks alpha 1 and alpha 2 receptor. Alpha 1 receptor is mainly found in the smooth muscles of blood vessels. Alpha 2 receptors are found in the peripheral and CNS. Alpha 1 receptor is blocks by this drug. This can lead to vasodilation and reduces the blood pressure. Blocking of alpha 2 receptors can have different effects on the nervous system like sedation, analgesia and reduces sympathetic tone.

 Pharmacokinetics:

Absorption

Phenoxybenzamine is absorbed slowly and incompletely from the gastrointestinal (GI) tract and with peak plasma concentrations occurring many hours after oral administration.

Distribution

Phenoxybenzamine has a large volume of distribution. It is distributed in the body. It is highly protein bound and mainly to albumin. It affects the distribution and elimination.

Metabolism

It is metabolized in the liver. Metabolite is N-phenoxyisopropyl-benzylamine.

Elimination and Excretion

The half-life of phenoxybenzamine is long about 24 to 48 hours. It is excreted in the urine and feces.

Adminstartion

Oral administration

Phenoxybenzamine is administered orally in the form of capsules. The recommended dosage of phenoxybenzamine may differ and it is depending on the condition of the patient, age, weight and other factors.

It must be taken with food or milk to lower the risk of GI upset. It is taken 2 to 3times a day and the doses are taken in timely manner. Patients may need to gradually increase the dosage over many days to weeks to get the proper therapeutic effects.

It can lead to orthostatic hypotension. It is sudden drop in blood pressure when you stand up from sitting or lying. Patients must be advised to sit and stand up slowly if they feel dizzy or lightheaded.

It is necessary to avoid drinking alcohol or taking other medications which can lead to drowsiness or dizziness while taking this medication.

It is necessary to take this drug under the guidance of healthcare provider and not to stop or change the dosage without any consultation. Sudden stop of this drug can cause rebound hypertension and increased blood pressure.

Patient Information Leaflet

Generic Name: phenoxybenzamine

Pronounced: [ fen-OX-ee-BENZ-a-meen ]

Why do we use phenoxybenzamine?

Phenoxybenzamine is a mainly used to treat conditions which can affect the blood vessels and urinary system. The main uses of this medications are:

To treat pheochromocytoma: It is rare tumor which is developed in adrenal gland. It can lead to high blood pressure, headaches, and other symptoms. It is used to manage the symptoms of this disease by blocking the effects of catecholamines.

To treat Raynaud’s disease: It is sued to enlarge the blood vessels and improve the blood flow to the affected areas.

To manage the autonomic dysreflexia: It is a serious condition. It can occur in patient who have spinal cord injuries. It is caused by unexpected increase in blood pressure. It can be life threatening. It is used to manage autonomic dysreflexia by blocking the effects to specific neurotransmitter which can trigger the condition.

To manage the urinary retention: It is sued to treat urinary retention. It is a condition in which the bladder is not able to empty completely. It can help to improve urine flow and reduce urinary retention by relaxing the smoot muscles in the bladder and urethra.