Phentolamine

Phentolamine is an Antihypertensive agent belonging to Alpha Adrenergic blockers.

Phentolamine is used in the treatment of Pheochromocytoma, Extravasation management, and Local anesthesia reversal. It is also used to treat Hypertensive crises; Extravasation of sympathomimetic vasopressors.

It is extensively metabolized in the liver and gets excreted Via urine (approx 13% as unchanged drug) with an elimination half-life of 19 minutes (IV).

The onset of Action of Phentolamine is within 1-2 minutes (IV); 15-20 minutes (IM).

The Duration of action of Phentolamine is 10-30 minutes (IV); 30-45 minutes (IM).

The Tmax of Phentolamine was within 7 minutes than for 15 minutes, and the Cmax of Phentolamine was found within 10.98 ng/mL

The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.

Phentolamine is available in the form of a dosage form, such as an injection.

Phentolamine is available in the USA, UK, Finland, Norway, Sweden, and India.

Phentolamine is a competitive and non-selective α-adrenergic blocker that briefly antagonizes the circulating norepinephrine and epinephrine, thus reducing hypertension caused by α effects of these catecholamines and decreasing tissue injury due to extravasation of these along with other sympathomimetic vasoconstrictors. It also has positive inotropic and chronotropic effects on the cardiac muscle.

Phentolamine is available in the form of a dosage form, such as an injection.

For fingertip ischemia, it is best to draw up the Phentolamine in a 1 ml syringe, then dilute it with 1% lidocaine. Use a 25- to 30-gauge needle. Insert the needle at the puncture site and slowly inject the solution. Multiple injections may be required if the area is large, but usually, one works.

Phentolamine is used in the treatment of Pheochromocytoma, Extravasation management, and Local anesthesia reversal. It is also used to treat Hypertensive crises; Extravasation of sympathomimetic vasopressors.

Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), leading to muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure. Phentolamine also stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart, and increases cardiac output.

Phentolamine is approved for its use in the following clinical indications:-

Although not approved, there have been certain label use documented for Phentolamine which includes:

Hypertensive crisis; Extravasation of sympathomimetic vasopressors

Phentolamine is available in various dosage strengths: 0.4mg/1.7mL, 5 mg.

Phentolamine is available in the form of a dosage form such as an injection.

Altered kidney function: No dosage adjustment is necessary for any degree of kidney dysfunction.

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed: No supplemental dose or dosage adjustment necessary.

Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound): No dosage adjustment necessary.

CRRT: No dosage adjustment necessary.

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary.

Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Severe impairment (Child-Pugh class C): Use is not recommended.

Diagnosis of Pheochromocytoma (Phentolamine blocking test):

The phentolamine-blocking test for the diagnosis of Pheochromocytoma has largely been supplanted by the measurement of catecholamine concentrations and catecholamine metabolites (eg, metanephrine) in the plasma and urine; reserve phentolamine for cases when additional confirmation is necessary to determine diagnosis.

IM: 3 mg.

IV: 1 mg.

Extravasation of sympathomimetic vasopressors (eg, dopamine, epinephrine, norepinephrine, phenylephrine), treatment: Limited data available for infants:

Infants, Children, and Adolescents: Infiltrate area of extravasation with a small amount (eg, 1 mL given in 0.2 mL aliquots) of a 0.5 to 1 mg/mL solution within 12 hours of extravasation (Total dose required depends on the size of extravasation; dose may be repeated if required. When reported, the total dose needed was 1 to 5 mL of a 1 mg/mL solution; however, other concentrations could be used.

Note: In the perioperative period, the use of other agents may be preferred due to the slow onset of action and prolonged Duration of Phentolamine in comparison to the other agents (eg, nitroprusside).

Preoperative: Children and Adolescents: IM, IV: 1 mg given 1 to 2 hours before surgery and repeat if needed.

Reversal of oral soft tissue (lip, tongue) anesthesia (Phentolamine ):

Amount of Local Anesthetic Administered Dose of Phentolamine

1/4 cartridge 1/4 cartridge (0.1 mg)

1/2 cartridge 1/2 cartridge (0.2 mg)

1 cartridge 1 cartridge (0.4 mg)

2 cartridges 2 cartridges (0.8 mg)

15 to <30 kg: 0.2 mg/dose.

≥30 kg: 0.8 mg/dose.

Phentolamine is approved for the treatment of Pheochromocytoma.

Foods high in tyramine, a substance that affects blood pressure, also can make symptoms worse. Tyramine is common in foods that are fermented, aged, pickled, cured, overripe or spoiled

Phentolamine may be contraindicated in the following

Hypersensitivity to Phentolamine, any component of the formulation, or related compounds; MI (or history of MI), coronary insufficiency, angina, or other evidence suggestive of coronary artery disease (excluding Phentolamine)

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Cardiovascular effects: MI, cerebrovascular spasm, and cerebrovascular occlusion have been reported following administration, usually associated with hypotensive episodes producing shock-like states. Tachycardia and cardiac arrhythmias may occur. Use with caution in patients with a history of cardiovascular disease. Discontinue if symptoms of angina occur or worsen.

• Appropriate use: The use of Phentolamine as a blocking agent in the screening of patients with hypertension has predominantly been replaced with urinary/biochemical assays; phentolamine use should be reserved for situations where additional confirmation is necessary and after risks associated with use have been considered.

It is not known if Phentolamine is present in breast milk. Due to the potential for serious adverse reaction in the breastfed infant, the decision to discontinue Phentolamine or discontinue breastfeeding during treatment should take into account the benefits of treatment to the mother.

Avoid taking alcohol with Phentolamine as it may result in side effects like headache, dizziness and faintness.

Administration of Phentolamine to pregnant rats and mice at oral doses 24 to 30 times the usual daily human dose (based on a 60 kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcanei and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. At oral doses 60 times the usual daily human dose (based on a 60 kg human), a slightly lower rate of implantation was found in the rat. Phentolamine did not affect embryonic or fetal development in the rabbit at oral doses 20 times the usual daily human dose (based on a 60 kg human). No teratogenic or embryotoxic effects were observed in the rat, mouse, or rabbit studies.

There are no adequate and well-controlled studies in pregnant women. Phentolamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Salt Substitutes: Those who are taking Phentolamine should avoid sodium, calcium and magnesium-rich foods. The salts may reduce the blood-pressure lowering effect of Phentolamine.

The adverse reactions related to molecule Phentolamine can be categorized as

● Common Adverse effect:

Cough ,headache, dizziness, drowsiness

● Less Common adverse effects:

Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower, hoarseness, difficulty breathing or swallowing, lightheadedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.

The clinically relevant drug interactions of Phentolamine is briefly summarized here.

When Phentolamine was administered as an intraoral submucosal injection 30 minutes after injection of a local anesthetic, 2% lidocaine HCl with 1:100,000 epinephrine, the lidocaine concentration increased immediately after Phentolamine intraoral injection. Lidocaine AUC and Cmax values were not affected by administration of Phentolamine . Phentolamine administration did not affect the PK of epinephrine.

Symptoms: CV disturbances (e.g., arrhythmias, hypotension, tachycardia, shock), excitation, headache, visual disturbances, sweating, pupillary contraction, nausea, vomiting, diarrhea, and hypoglycemia.

Management: Supportive treatment. Raise the patient's leg and administer plasma expander. May give IV infusion of norepinephrine, if necessary, then titrate to maintain blood pressure at normotensive level; do not use epinephrine.

Phentolamine is a competitive and non-selective α-adrenergic blocker that briefly antagonizes the circulating norepinephrine and epinephrine, thus reducing hypertension caused by α effects of these catecholamines and decreasing tissue injury due to extravasation of these along with other sympathomimetic vasoconstrictors. It also has positive inotropic and chronotropic effects on the cardiac muscle.

There are some clinical studies of the drug Phentolamine mentioned below: