PHENYLEPHRINE HCL

Chemistry - An alpha-adrenergic sympathomimetic amine, phenylephrine HCl occurs as bittertasting, odorless, white to nearly white crystals with a melting point of 145 - 146°C. It is freelysoluble 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 occurwithout a color change. To protect against oxidation, the air in commercially available ampules forinjection 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, potassiumchloride, and sodium bicarbonate. While stated to be incompatible with alkalies, it is stable withsodium bicarbonate solutions. Phenylephrine is reported to be incompatible with ferric salts, oxidizing agents, and metals.

Pharmacology - PHENYLEPHRINE HCL

Phenylephrine has predominantly post-synaptic alpha-adrenergic effects attherapeutic doses. At usual doses it has negligible beta effects, but beta effects can occur at highdoses.
Phenylephrine's primary effects, when given intravenously, include peripheral vasoconstrictionwith resultant increase in diastolic and systolic blood pressures, small decreases in cardiac outputand an increase in circulation time. A reflex bradycardia (blocked by atropine) can occur. Mostvascular beds are constricted (renal splanchnic, pulmonary, cutaneous), but coronary blood flow isincreased. Its alpha effects can cause contraction of the pregnant uterus and constriction of uterineblood vessels.

Uses, Indications

Phenylephrine has been used to treat hypotension and shock (after adequatevolume replacement), but many clinicians prefer to use an agent that also has cardiostimulatoryproperties. It may be of benefit, however, when cardiostimulation would be undesirable, such asduring general anesthesia (halothane) or if the patient is also receiving other agents that sensitize themyocardium. Phenylephrine is recommended to be used to treat hypotension secondary to drugoverdoses or idiosyncratic hypotensive reactions to drugs such as phenothiazines, adrenergicblocking agents, and ganglionic blockers. Its use to treat hypotension resulting from barbiturate orother CNS depressant agents is controversial. Phenylephrine has been used to increase bloodpressure to terminate attacks of paroxysmal supraventricular tachycardia, particularly when thepatient is also hypotensive. Phenylephrine has been used to treat both hypotension and to prolongthe effects of spinal anesthesia.
Ophthalmic uses of phenylephrine include use for some diagnostic eye examinations, to reduceposterior synchiae formation and relieve pain associated with complicated uveitis. It has beenapplied intranasally in an attempt to reduce nasal congestion.

Pharmacokinetics - PHENYLEPHRINE HCL

After oral administration, phenylephrine is rapidly metabolized in the GI tractand cardiovascular effects are generally unattainable via this route of administration. Following IVadministration, pressor effects begin almost immediately and will persist for up to 20 minutes. Theonset of pressor action after IM administration is usually within 10-15 minutes, and will last forapproximately one hour.
It is unknown if phenylephrine is excreted into milk. It is metabolized by the liver, and the effectsof 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 extremecaution in geriatric patients, patients with hyperthyroidism, bradycardia, partial heart block or withother heart disease. Phenylephrine is not a replacement for adequate volume therapy in patients withshock.

Adverse Effects, Warnings

At usual doses, a reflex bradycardia, CNS effects (excitement, restlessness, headache) and, rarely, arrhythmias are seen. Blood pressure must be monitored toprevent 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 mlof normal saline. A syringe with a fine needle should be used to infiltrate the site with manyinjections.
Overdosage - Overdosage of phenylephrine can cause hypertension, seizures, vomiting, paresthesias, ventricular extrasystoles and cerebral hemorrhage. Hypertension, if severe, can be treated bythe administration of phentolamine (an alpha blocking agent). Should cardiac arrhythmias requiretreatment, use a beta-blocking drug such as propranolol.

Drug Interactions

Higher dosages of phenylephrine may be required to attain a pressor effect, ifphenothiazines 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.