Chemistry - An alpha-adrenergic sympathomimetic amine, phenylephrine HCl occurs as bitter-tasting, odorless, white to nearly white crystals with a melting point of 145 - 146°C. It is freely soluble in water and alcohol. The pH of the commercially available injection is 3.0 - 6.5.
Storage/Stability/Compatibility - The injectable product should be stored protected from light. Do not use solutions if they are brown or contain a precipitate. Oxidation of the drug can occur without a color change. To protect against oxidation, the air in commercially available ampules for injection is replaced with nitrogen and a sulfite added.
Phenylephrine is reported to be compatible with all commonly used IV solutions and the following drugs: chloramphenicol sodium succinate, dobutamine HCl, lidocaine HCl, potassium chloride, and sodium bicarbonate. While stated to be incompatible with alkalies, it is stable with sodium bicarbonate solutions. Phenylephrine is reported to be incompatible with ferric salts, oxidizing agents, and metals.
Pharmacology - Phenylephrine has predominantly post-synaptic alpha-adrenergic effects at therapeutic doses. At usual doses it has negligible beta effects, but beta effects can occur at high doses.
Phenylephrine’s primary effects, when given intravenously, include peripheral vasoconstriction with resultant increase in diastolic and systolic blood pressures, small decreases in cardiac output and an increase in circulation time. A reflex bradycardia (blocked by atropine) can occur. Most vascular beds are constricted (renal splanchnic, pulmonary, cutaneous), but coronary blood flow is increased. Its alpha effects can cause contraction of the pregnant uterus and constriction of uterine blood vessels.
Uses/Indications - Phenylephrine has been used to treat hypotension and shock (after adequate volume replacement), but many clinicians prefer to use an agent that also has cardiostimulatory properties. It may be of benefit, however, when cardiostimulation would be undesirable, such as during general anesthesia (halothane) or if the patient is also receiving other agents that sensitize the myocardium. Phenylephrine is recommended to be used to treat hypotension secondary to drug overdoses or idiosyncratic hypotensive reactions to drugs such as phenothiazines, adrenergic blocking agents, and ganglionic blockers. Its use to treat hypotension resulting from barbiturate or other CNS depressant agents is controversial. Phenylephrine has been used to increase blood pressure to terminate attacks of paroxysmal supraventricular tachycardia, particularly when the patient is also hypotensive. Phenylephrine has been used to treat both hypotension and to prolong the effects of spinal anesthesia.
Ophthalmic uses of phenylephrine include use for some diagnostic eye examinations, to reduce posterior synchiae formation and relieve pain associated with complicated uveitis. It has been applied intranasally in an attempt to reduce nasal congestion.
Pharmacokinetics - After oral administration, phenylephrine is rapidly metabolized in the GI tract and cardiovascular effects are generally unattainable via this route of administration. Following IV administration, pressor effects begin almost immediately and will persist for up to 20 minutes. The onset of pressor action after IM administration is usually within 10-15 minutes, and will last for approximately one hour.
It is unknown if phenylephrine is excreted into milk. It is metabolized by the liver, and the effects of the drug are also terminated by uptake into tissues.
Contraindications/Precautions - Phenylephrine is contraindicated in patients with severe hypertension, ventricular tachycardia or those who are hypersensitive to it. It should be used with extreme caution in geriatric patients, patients with hyperthyroidism, bradycardia, partial heart block or with other heart disease. Phenylephrine is not a replacement for adequate volume therapy in patients with shock.
Adverse Effects/Warnings - At usual doses, a reflex bradycardia, CNS effects (excitement, restlessness, headache) and, rarely, arrhythmias are seen. Blood pressure must be monitored to prevent hypertension.
Extravasation injuries with phenylephrine can be very serious (necrosis and sloughing of surrounding tissue). Patient’s IV sites should be routinely monitored. Should extravasation occur, infiltrate the site (ischemic areas) with a solution of 5-10 mg phentolamine (Regitine®) in 10-15 ml of normal saline. A syringe with a fine needle should be used to infiltrate the site with many injections.
Overdosage - Overdosage of phenylephrine can cause hypertension, seizures, vomiting, paresthesias, ventricular extrasystoles and cerebral hemorrhage. Hypertension, if severe, can be treated by the administration of phentolamine (an alpha blocking agent). Should cardiac arrhythmias require treatment, use a beta-blocking drug such as propranolol.
Drug Interactions - Higher dosages of phenylephrine may be required to attain a pressor effect, if phenothiazines or an alpha-blocking agent (phentolamine) have been used prior to therapy. Phenylephrine may induce cardiac arrhythmias when used with halothane anesthesia or in digitalized patients. When used concurrently with oxytocic agents, pressor effects may be enhanced. Atropine will block the reflex bradycardia that phenylephrine causes. Monoamine oxidase (MAO) inhibitors should not be used with phenylephrine because of a pronounced pressor effect.
a) 5 mg IV (Enos and Keiser 1985)
Monitoring Parameters -
1) Cardiac rate/rhythm
2) Blood pressure, and blood gases if possible
Client Information - Parenteral phenylephrine should only be used by professionals in a setting where adequate monitoring is possible.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Phenylephrine HCl for Injection 10 mg/ml in ml amps; Neo-Synephrine® ((Sanofi Winthrop); generic; (Rx)
Phenylephrine is also available in ophthalmic and intranasal dosage forms and in combination with antihistamines, analgesics, decongestants, etc., for oral administration in humans.
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