Phenylephrine

Phenylephrine is a vasoconstrictor and belongs to the group of direct sympathomimetics. These bind to one or more subtypes of adrenoceptors and are therefore also called adrenoceptor agonists. Phenylephrine binds specifically to the _{α1-adrenoceptor}, which is activated by the signaling agents epinephrine and norepinephrine. Its binding triggers versatile effects, making the drug versatile in its use.

Applications and indications

Phenylephrine can be found as an active ingredient in nasal drops to reduce swelling of the mucous membranes or in combination preparations with, for example, paracetamol to relieve cold symptoms (^GeloProsed®). Furthermore, film-coated tablets in combination with ibuprofen are also available on the market, also to alleviate cold symptoms. In the area of the eye, it is used in the form of eye drops, for example as a mydriatic to briefly dilate the pupils for medical examinations or to constrict the blood vessels in the conjunctiva. In medicines for internal use, the chlorine salt phenylephrine hydrochloride is used because it is more water-soluble and thus can be dissolved and absorbed more quickly after ingestion. This leads to a faster onset of action. The active ingredient can thus be used in injection/infusion solutions and is also used in the field of anesthesia as a vasopressor to raise blood pressure.

It is also commercially available in combination with other active ingredients as film-coated tablets.

Eye drops containing the active ingredient phenylephrine (e.g., Neosynephrine-POS 5%) are applied to the eye once or twice daily at a dose of one drop with the head reclined.

Vibrocil nasal spray is sprayed into the nose in acute rhinitis to decongest the nasal mucosa, thus facilitating nasal breathing. The dose allowed according to the package leaflet is 2 sprays per nostril three to four times a day in adults; in children 6-12 years of age, only one spray in each nostril is allowed three to four times a day.

These and similar preparations containing the active ingredient phenylephrine should be used for short periods only and are not suitable for long-term use. They should be used only for short-term symptoms of a flu-like infection in the case of cold preparations, or in the context of an eye examination/eye inflammation.

In general, use should not exceed the duration of one week without medical consultation.

Injection solutions such as Phenylephrine Aguettant are administered under the direction of a physician and by a medical professional. In this process, the doctor determines the dose according to the patient's medical history.

There are different dosages of these injection solutions; a normal dosage is 50 to 100 micrograms and may be repeated. However, a bolus injection (i.e., when the substance is administered quickly) must not exceed the 100 micrograms.

Pharmacodynamics/mechanism of action

Phenylephrine has a sympathomimetic effect, which means that it triggers the functions of the sympathetic nervous system, which aim to increase activity through nervous messages, by binding to the _{α1-adrenoceptor}. These receptors are mostly located in the central nervous system and are used both locally- for example in the form of nasal drops- and systemically as injection/infusion solutions and lead to vasoconstriction. That is, after ingestion, phenylephrine binds to _{α1-adrenoceptors}, which subsequently constricts the blood vessels in the body. The vascular muscles are tightened, so the lumen of the vessels is narrowed and consequently the blood flow decreases. As a result, the mucosa swells and triggers desirable effects such as unblocking of a stuffy nose as well as reduction of runny nose or alleviation of puffy eyes, as appropriate.

Pharmacokinetics

For injectable solutions, phenylephrine is effective 20 minutes after intravenous administration.

The drug is metabolized in the liver via monoamine oxidase (resulting in low oral bioavailability) and excreted primarily by the kidney.

The half-life (the time in which the level of the active ingredient has already decreased to half) for injected phenylephrine is approximately three hours.

Structurally, phenylephrine is a very low polar compound and therefore can be readily absorbed from the gastrointestinal tract.

Drug Interactions

• Different groups of antidepressants (tricyclic antidepressants, noradrenergic-serotonergic antidepressants) and sibutramine in combination with phenylephrine induce paroxysmal (suddenly recurring) hypertension and increase the risk of arrhythmias.
• Cardiac glycosides and quinidine likewise increase the risk of arrhythmias.
• Selective MAO (monoamine oxidase) A inhibitors and linezolid increase the risk of vasoconstriction (vasoconstriction) and/or hypertensive crisis.
• Guanethidine and similar products used to treat hypertension may interact with phenylephrine to cause a marked increase in blood pressure.
• Halogenated volatile anesthetics such as isoflurane, in the presence of phenylephrine, increase the risk of hypertensive crisis and arrhythmias perioperatively (i.e., in the period before, during, and after surgery)
• When taken concomitantly with beta blockers, phenylephrine should be taken at a lower dose, as transient dyspnea and blood pressure elevation may occur in rare cases.
• Alpha receptor blockers cancel the effect of phenylephrine.

When phenylephrine is used concomitantly with other sympathomimetics, their effects may be enhanced or attenuated.

Therefore, before taking a drug with phenylephrine, it is important to tell the doctor to be treated which drugs are being taken at the same time.

Contraindications & precautions

MAO inhibitors (monoamine oxidase inhibitors) are psychotropic drugs used for depression. They aben a long-lasting effect and may interact with phenylephrine even after 15 days since the last dose and cause effects such as hypertension or hyperthermia. In that case, this is a clear contraindicated combination and should be avoided.

Medicines containing phenylephrine should be used with caution and after consultation with a physician in patients with the following conditions:

• Hypertension (high blood pressure)
• Cardiac arrhythmias such as bradycardia (slowing of the heartbeat), tachycardia (increase in the heartbeat) or arrhythmia: in this case, a reduction of the dose should be considered, as well as monitoring of vital organ functions during the period of use
• coronary/chronic heart disease
• Aneurysm (local bulging of the blood vessel)
• hyperthyroidism (overactive thyroid gland)

Phenylephrine affects the heart and may cause a reduction in cardiac output. Therefore, special care must be taken in elderly patients as well as in patients with arteriosclerosis!

Likewise, caution is advised in combination with oxytocics, as the effect is potentiated and consequently persistent (continuing) hypertension and postpartum (after birth) strokes may occur.

Long-term use of the drug in the nose or eye is prohibited.

Side effects

Phenylephrine is commonly used as an injection solution in critical care patients with hypotension and shock. Side effects that may occur include:

• immune system disorders: hypersensitivity
• Nervous system disorders: headache
• Psychiatric disorders: Anxiety, restlessness, confusion
• Heart diseases: tachycardia, hypertension (high blood pressure), arrhythmia, angina pectoris (chest tightness)
• Vascular disorders: cerebral hemorrhage, hypertensive crisis
• Respiratory/thoracic disorders: dyspnea (shortness of breath, shortness of breath), pulmonary edema
• Gastrointestinal disorders: nausea, vomiting
• Skin disorders: sweating, pallor
• Kidney and urinary tract disorders: urinary retention, difficulty urinating

The frequency with which these side effects occur is not known and they are mainly related to different underlying diseases of the patients and not necessarily to the use of the drug itself.

When phenylephrine is used in the form of eye drops or nasal drops, it is only slightly absorbed into blood and therefore severe systemic side effects are not expected. Possible side effects include reddening eyes and burning pain. Accommodative disorders such as blurred vision may also occur.

When used in the nose, increased secretion and mucosal damage, among other things, are possible.

Pregnancy and lactation

It is possible to inject phenylephrine during pregnancy under strict guidelines, but this should be avoided toward the end of pregnancy or during labor because of the potential for fetal hypoxia (hypoxia of the unborn child) or bradycardia.

During breastfeeding, medications containing phenylephrine should be avoided because the nursing infant is at risk for cardiovascular or neurological effects. Small amounts of phenylephrine may pass into breast milk. Oral bioavailability is then low, but it should still not be taken.