Description of Phentolamine
Phentolamine is an alpha-adrenergic receptor antagonist. Phentolamine is similar in action to phenoxybenzamine but is administered parenterally and has a shorter duration of action. Approved uses of phentolamine include diagnosis of pheochromocytoma and treatment of hypertension in pheochromocytoma, prevention of tissue necrosis after norepinephrine extravasation, and reversal of soft tissue anesthesia. Phentolamine also has been used to treat hypertensive crisis associated with monoamine oxidase inhibitor (MAOI) therapy and in combination with papaverine to treat erectile dysfunction (ED). According to ED treatment guidelines, oral phosphodiesterase type 5 (PDE5) inhibitors are considered first-line therapy. Second-line treatment options include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and carries notable side-effects including priapism and penile fibrosis. Phentolamine injection is contraindicated for use in patients with any coronary artery disease due to cardiac stimulating effects and corresponding increase in myocardial oxygen demand. Phentolamine was FDA-approved in 1952.
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Mechanism of Action of Phentolamine
Phentolamine is a potent short-acting, competitive antagonist of alpha-adrenergic receptors. Like phenoxybenzamine, phentolamine antagonizes both alpha1– and alpha2-receptors. Prazosin, another alpha-receptor antagonist, differs from both of these agents in that it is selective for the alpha1-receptor.
Phentolamine reduces peripheral resistance via antagonism of the alpha1-receptors and possibly alpha2-receptors on vascular smooth muscle. Antagonism at alpha2-receptors cause cardiac stimulation due to an enhanced release of norepinephrine from sympathetic nerves. Phentolamine has positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle. The clinical effects of phentolamine include cardiac stimulation caused by a decrease in peripheral resistance and an increase in cardiac output. Postural hypotension is often observed accompanied by reflex tachycardia that can precipitate cardiac arrhythmias and myocardial ischemia. These actions make phentolamine useful in treating hypertension caused by increased circulating levels of epinephrine and norepinephrine, as occurs in pheochromocytoma.
The effects of phentolamine in treating erectile dysfunction are mediated by alpha-adrenergic blockade in penile blood vessels. The drug’s actions cause relaxation of the trabecular cavernous smooth muscles and dilation of the penile arteries, which increases arterial blood flow into the corpus cavernosa and subsequently causes an erection. The glans and corpus spongiosum swell minimally, if at all.
The mechanism by which OraVerse (phentolamine injection for dental use) produces reversal of soft tissue anesthesia and associated functional deficits is not fully understood.
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Pharmacokinetics of Phentolamine
Phentolamine is primarily administered intravenously or intramuscularly. It can also be given subcutaneously to prevent local tissue necrosis when vasoconstrictor drugs extravasate, or it can be given by infiltration or nerve block for reversal of soft tissue anesthesia. The pharmacokinetics of phentolamine are largely unknown. Following IV administration of a single dose, approximately 13% of the dose is excreted in urine unchanged. The half-life of the drug in blood is 19 minutes following intravenous administration.
•Route-Specific Pharmacokinetics
Other Route(s)
Submucosal Route
After phentolamine (OraVerse) administration, 100% of the drug is available. Peak concentrations occur in 10 to 20 minutes, and systemic exposure increases linearly with increasing dosages. The half-life of phentolamine after submucosal administration is 2 to 3 hours.
- Phentolamine Mesylate
- Regitine
- OraVerse
- Alpha-Adrenergic Blocker
- Antidote
- Antihypertensive
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Adult
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Pediatric
- Injection site extravasation; Treatment and Prophylaxis – Norepinephrine adverse reaction: Adult
- Injection site extravasation; Treatment and Prophylaxis – Norepinephrine adverse reaction: Pediatric
- Pheochromocytoma; Diagnosis: Adult
- Pheochromocytoma; Diagnosis: Pediatric
- Procedure on oral cavity – Reversal of anesthesia, Soft-tissue: Adult
- Procedure on oral cavity – Reversal of anesthesia, Soft-tissue: Pediatric: yes (3 years and older)
- Dermatologic: Injection site pain (4% to 6% )
- Gastrointestinal: Diarrhea (less than 3% )
- Respiratory: Nasal congestion (10% )
- Other: Posttreatment pain (up to 10% )
- Cardiovascular: Cardiac dysrhythmia, Chest pain, Hypotension, Myocardial infarction
- Neurologic: CVA – cerebrovascular accident due to cerebral artery occlusion
- Intravenous: May be injected rapidly
- Intravenous: May be given IV or IM
- Intravenous: (Sandoz Canada product) Reconstitution not required
- Intravenous: (Sandoz Canada product) Refrigerate vial; protect from heat and light
- Intravenous: (US product) Reconstitute with Sterile Water for Injection to a concentration of 5 mg/mL
- Intravenous: (US product) Reconstituted solution should be used upon preparation; do not store
- Intramuscular: (US product) Reconstitute with Sterile Water for Injection to a concentration of 5 mg/mL
- Intramuscular: (US product) Reconstituted solution should be used upon preparation; do not store
- Intramuscular: (Sandoz Canada product) Reconstitution not required
- Intramuscular: (Sandoz Canada product) Refrigerate vial; protect from heat and light
- Intramuscular: May be given IV or IM
- Intramuscular: May be injected rapidly for the diagnosis of pheochromocytoma
- Intravenous: May be injected rapidly for the diagnosis of pheochromocytoma
- Injection, periodontal: Location(s) and technique(s) (infiltration or block injection) should be the same as used for the local anesthetic/vasoconstrictor .
- Injection Powder for Solution: 5 MG
- Important Note: Due to a critical shortage of phentolamine mesylate for injection, the temporary importation of Sandoz Canada’s phentolamine mesylate injection 5 mg/mL product to the United States has been initiated. Contact Sandoz Inc. Customer Service at 1-800-525-8747 Monday to Friday between 8:30 AM and 5:30 PM Eastern Standard Time for ordering information .
- Erectile dysfunction: 40 to 80 mg ORALLY 1 hr prior to sexual activity
- Hypertension: Hypertensive emergency: 5 mg IV bolus; additional bolus doses every 10 minutes as needed to lower blood pressure (BP) to target (guideline dosage)
- Hypertension: Target BP, for pheochromocytoma crisis, rapidly lower systolic pressure to less than 140 mm Hg during first hour; otherwise, reduce BP by up to 25% over first hour then to 160/100 to 110 mm Hg over the next 2 to 6 hours, then to normal over the next 24 to 48 hours (guideline dosage)
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Preoperative, 5 mg IV or IM 1 to 2 hours prior to surgery, may repeat as needed (FDA dosage)
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Intraoperative, 5 mg IV as needed (FDA dosage)
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Pheochromocytoma crisis, 5 mg IV repeated every 10 minutes as needed to rapidly lower systolic blood pressure to less than 140 mm Hg during first hour (guideline dosage)
- Injection site extravasation; Treatment and Prophylaxis – Norepinephrine adverse reaction: prevention, 10 mg added to each liter of solution containing norepinephrine
- Injection site extravasation; Treatment and Prophylaxis – Norepinephrine adverse reaction: treatment, 5 to 10 mg in 10 mL saline SC infiltrated within 12 hr into area of extravasation
- Pheochromocytoma; Diagnosis: 5 mg IV or IM
- Procedure on oral cavity – Reversal of anesthesia, Soft-tissue: 0.1 mg for every 1/4 cartridge of local anesthetic administered, 0.2 mg for every 1/2 cartridge of local anesthetic administered, 0.4 mg for every 1 cartridge of local anesthetic administered, and 0.8 mg for 2 cartridges of local anesthetic administered; location(s) and technique(s) (infiltration or block injection) should be the same as used for the local anesthetic/vasoconstrictor
- Important Note: Due to a critical shortage of phentolamine mesylate for injection, the temporary importation of Sandoz Canada’s phentolamine mesylate injection 5 mg/mL product to the United States has been initiated. Contact Sandoz Inc. Customer Service at 1-800-525-8747 Monday to Friday between 8:30 AM and 5:30 PM Eastern Standard Time for ordering information .
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Preoperative, 1 mg IV or IM 1 to 2 hours prior to surgery, may repeat as needed
- Increased blood pressure, Pre- or intra-operative; Treatment and Prophylaxis – Pheochromocytoma: Intraoperative, 1 mg IV as needed
- Pheochromocytoma; Diagnosis: 1 mg IV or 3 mg IM
- Procedure on oral cavity – Reversal of anesthesia, Soft-tissue: (4 years and older) 0.1 mg for 1/4 cartridge of local anesthetic administered, 0.2 mg for 1/2 cartridge of local anesthetic administered, 0.4 mg for 1 cartridge of local anesthetic administered, and 0.8 mg for 2 cartridges of local anesthetic administered; location(s) and technique(s) (infiltration or block injection) should be the same as used for the local anesthetic/vasoconstrictor; MAX dose is 0.2 mg in children weighing 15 to less than 30 kg
- Procedure on oral cavity – Reversal of anesthesia, Soft-tissue: (3 to less than 4 years) 0.1 mg for 1/4 cartridge of local anesthetic administered, 0.2 mg for 1/2 cartridge of local anesthetic administered, and 0.4 mg for 1 cartridge of local anesthetic administered; location(s) and technique(s) (infiltration or block injection) should be the same as used for the local anesthetic/vasoconstrictor; MAX dose is 0.2 mg in children weighing 15 to less than 30 kg