PHENOXYBENZAMINE HCL
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 mgis soluble in 1 ml of water and 167 mg is soluble in 1 ml of alcohol.
Phenoxybenzamine causes cutaneous blood flow to increase, but little effects are noted on skeletalor cerebral blood flow. Phenoxybenzamine can also block pupillary dilation, lid retraction, andnictitating membrane contraction. Both standing and supine blood pressures are decreased inhumans.
Uses, Indications - Phenoxybenzamine is used in small animals primarily for its effect in reducinginternal urethral sphincter tone in dogs and cats when urethral sphincter hypertonus is present. Itcan also be used to treat the hypertension associated with pheochromocytoma prior to surgery or asadjunctive therapy in endotoxicosis.
In horses, phenoxybenzamine has been used for preventing or treating laminitis in its early stagesand to treat secretory diarrheas.
Phenoxybenzamine is highly lipid soluble and may accumulate in body fat. It is unknown ifphenoxybenzamine 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 inboth the urine and bile.
Contraindications/Precautions - Phenoxybenzamine is contraindicated in horses with symptomsof colic and in patients when symptoms of hypotension would be undesirable (e.g., shock, unlessfluid replacement is adequate). One author (Labato 1988) lists glaucoma and diabetes mellitus ascontraindications for the use of phenoxybenzamine in dogs.
Phenoxybenzamine should be used with caution in patients with CHF or other heart disease asdrug-induced tachycardia can occur. It should be used cautiously in patients with renal damage orcerebral/coronary arteriosclerosis.
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 iscontraindicated (see Drug Interactions) and most vasopressor drugs are ineffective in reversing theeffects of alpha-blockade. Intravenous norepinephrine (levarterenol) may be beneficial, however, ifsymptoms are severe.
If used with drugs that have both alpha- and beta-adrenergic effects (e.g., epinephrine), increased hypotension, vasodilatation or tachycardia may result.
Storage, Stability, Compatibility
Phenoxybenzamine capsules should be stored at room temperature in well-closed containers.Pharmacology - PHENOXYBENZAMINE HCL
Alpha-adrenergic response to circulating epinephrine or norepinepinephrine isnoncompetitively blocked by phenoxybenzamine. The effects of phenoxybenzamine have beendescribed as a "chemical sympathectomy". No effects on beta-adrenergic receptors or on theparasympathetic nervous system occur.Phenoxybenzamine causes cutaneous blood flow to increase, but little effects are noted on skeletalor cerebral blood flow. Phenoxybenzamine can also block pupillary dilation, lid retraction, andnictitating membrane contraction. Both standing and supine blood pressures are decreased inhumans.
Uses, Indications - Phenoxybenzamine is used in small animals primarily for its effect in reducinginternal urethral sphincter tone in dogs and cats when urethral sphincter hypertonus is present. Itcan also be used to treat the hypertension associated with pheochromocytoma prior to surgery or asadjunctive therapy in endotoxicosis.
In horses, phenoxybenzamine has been used for preventing or treating laminitis in its early stagesand to treat secretory diarrheas.
Pharmacokinetics - PHENOXYBENZAMINE HCL
No information was located on the pharmacokinetics of this agent in veterinary species. In humans, phenoxybenzamine is variably absorbed from the GI, with a bioavailabilityof 20-30%. Onset of action of the drug is slow (several hours) and increases over several days afterregular 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 ifphenoxybenzamine 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 inboth the urine and bile.
Contraindications/Precautions - Phenoxybenzamine is contraindicated in horses with symptomsof colic and in patients when symptoms of hypotension would be undesirable (e.g., shock, unlessfluid replacement is adequate). One author (Labato 1988) lists glaucoma and diabetes mellitus ascontraindications for the use of phenoxybenzamine in dogs.
Phenoxybenzamine should be used with caution in patients with CHF or other heart disease asdrug-induced tachycardia can occur. It should be used cautiously in patients with renal damage orcerebral/coronary arteriosclerosis.
Adverse Effects, Warnings
Adverse effects associated with alpha-adrenergic blockade include:hypotension, hypertension, miosis, increased intraocular pressure, tachycardia, inhibition ofejaculation 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 iscontraindicated (see Drug Interactions) and most vasopressor drugs are ineffective in reversing theeffects of alpha-blockade. Intravenous norepinephrine (levarterenol) may be beneficial, however, ifsymptoms 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 beta-adrenergic effects (e.g., epinephrine), increased hypotension, vasodilatation or tachycardia may result.