Chemistry - An alpha-adrenergic blocking agent, phenoxybenzamine HCl occurs as an odorless, white crystalline powder with a melting range of 136°-141° and a pKa of 4.4. Approximately 40 mg is soluble in 1 ml of water and 167 mg is soluble in 1 ml of alcohol.
Storage/Stability/Compatibility - Phenoxybenzamine capsules should be stored at room temperature in well-closed containers.
Pharmacology - Alpha-adrenergic response to circulating epinephrine or norepinepinephrine is noncompetitively blocked by phenoxybenzamine. The effects of phenoxybenzamine have been described as a “chemical sympathectomy”. No effects on beta-adrenergic receptors or on the parasympathetic nervous system occur.
Phenoxybenzamine causes cutaneous blood flow to increase, but little effects are noted on skeletal or cerebral blood flow. Phenoxybenzamine can also block pupillary dilation, lid retraction, and nictitating membrane contraction. Both standing and supine blood pressures are decreased in humans.
Uses/Indications - Phenoxybenzamine is used in small animals primarily for its effect in reducing internal urethral sphincter tone in dogs and cats when urethral sphincter hypertonus is present. It can also be used to treat the hypertension associated with pheochromocytoma prior to surgery or as adjunctive therapy in endotoxicosis.
In horses, phenoxybenzamine has been used for preventing or treating laminitis in its early stages and to treat secretory diarrheas.
Pharmacokinetics - No information was located on the pharmacokinetics of this agent in veterinary species. In humans, phenoxybenzamine is variably absorbed from the GI, with a bioavailability of 20-30%. Onset of action of the drug is slow (several hours) and increases over several days after regular dosing. Effects persist for 3-4 days after discontinuation of the drug.
Phenoxybenzamine is highly lipid soluble and may accumulate in body fat. It is unknown if phenoxybenzamine crosses the placenta or is excreted into milk. The serum half-life of phenoxybenzamine is approximately 24 hours in humans. It is metabolized (dealkylated) and excreted in both the urine and bile.
Contraindications/Precautions - Phenoxybenzamine is contraindicated in horses with symptoms of colic and in patients when symptoms of hypotension would be undesirable (e.g., shock, unless fluid replacement is adequate). One author (Labato 1988) lists glaucoma and diabetes mellitus as contraindications for the use of phenoxybenzamine in dogs.
Phenoxybenzamine should be used with caution in patients with CHF or other heart disease as drug-induced tachycardia can occur. It should be used cautiously in patients with renal damage or cerebral/coronary arteriosclerosis.
Adverse Effects/Warnings - Adverse effects associated with alpha-adrenergic blockade include: hypotension, hypertension, miosis, increased intraocular pressure, tachycardia, inhibition of ejaculation and nasal congestion. Additionally, it can cause weakness/dizziness and GI effects (e.g., nausea, vomiting). Constipation may occur in horses.
Overdosage - Overdosage of phenoxybenzamine may yield signs of postural hypotension (dizziness, syncope), tachycardia, vomiting, lethargy or shock.
Treatment should consist of emptying the gut if the ingestion was recent and there are no contraindications to those procedures. Hypotension can be treated with fluid support. Epinephrine is contraindicated (see Drug Interactions) and most vasopressor drugs are ineffective in reversing the effects of alpha-blockade. Intravenous norepinephrine (levarterenol) may be beneficial, however, if symptoms are severe.
Drug Interactions - Phenoxybenzamine will antagonize the effects of alpha-adrenergic sympathomimetic agents (e.g., phenylephrine). If used with drugs that have both alpha and betaadrenergic effects (e.g., epinephrine), increased hypotension, vasodilatation or tachycardia may result.
Doses - Note:Because the only dosage form available is a 10 mg capsule, doses should be rounded to the nearest 2.5 mg dose when possible.
a) 0.66 mg/kg in 500 ml saline IV (Robinson 1987)
b) 1.2 mg/kg PO, followed in 12 hours by 0.6 mg/kg PO for 2 doses (Schultz 1986)
c) 200 - 600 mg q12h for treatment of profuse, watery diarrhea. (Clark 1988)
Monitoring Parameters - 1) Clinical efficacy (adequate urination, etc.) 2) Blood pressure, if necessary/possible
Client Information - Contact veterinarian if animal has continuing problems with weakness, appears dizzy or collapses after standing, or has persistent vomiting. GI upset may be reduced if the drug is given with meals.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Phenoxybenzamine HCl 10 mg Capsules; Dibenzyline® (;SKF); (Rx)
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