Phenylephrine

Decongestant Phenylephrine is used as an alternative to pseudoephedrine as a decongestant, the availability of which has been restricted in some countries due to a potential for use in the illicit synthesis of methamphetamine. Its efficacy as an oral decongestant has been questioned, with several independent studies finding that it provided no more relief to sinus congestion than a placebo. A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient, though another meta-analysis published shortly thereafter by researchers from GlaxoSmithKline found the standard 10-mg dose to be more effective than a placebo; however, the fact that GSK markets many products containing phenylephrine has raised some speculation regarding selective publishing and other controversial techniques. A 2007 study by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage. The Food and Drug Administration withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007. Phenylephrine has been off-patent since 1950, The committee also unanimously believes that this does not need further study. The FDA responded to the committee, stating it would take its advice under advisement. In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion. Phenylephrine can be used topically to prevent symptoms of hemorrhoids. Phenylephrine causes the constriction of vascular smooth muscle and is often used in the treatment of hemorrhoids to narrow the swollen veins and relieve the attendant pain. However, veins contain less vascular smooth muscle in their walls than arteries. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when feces are passed. Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in suppository formulations for hemorrhoid treatment. Pupil dilation Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is often used in combination with tropicamide as a synergist when tropicamide alone is not sufficient. Narrow-angle glaucoma is a contraindication to phenylephrine use. As a mydriatic, it is available in 2.5% and 10% eye drops. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied. Intraocular bleeding Phenylephrine has been used as an intracameral injection into the anterior chamber of the eye to arrest intraocular bleeding occurring during cataract and glaucoma surgery. Low blood pressure Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension (low blood pressure), especially resulting from septic shock. Such use is common in surgery and anesthesia or critical-care practices; In clinical studies, intravenous phenylephrine increases blood pressure, decreases cardiac output, increases cerebral blood flow, and decreases cerebral tissue oxygen saturation. It has been found to improve vascular resistance, enhance circulatory support, and improve symptoms of orthostatic intolerance in people with the condition. Available forms Phenylephrine is available in the form of oral tablets and syrups for use as a nasal decongestant, as an intravenous solution to treat hypotension, as an ophthalmic solution, spray, or eye drop to cause pupil dilation, and as a cocoa butter suppository, among other forms. It was also previously available as a metered aerosol for inhalation, but this formulation was discontinued. Phenylephrine is available both alone and in combination with other drugs. These other drugs include antihistamines like chlorpheniramine, doxylamine, promethazine, and mepyramine (pyrilamine); analgesics like paracetamol (acetaminophen), ibuprofen, ketorolac, and codeine; cough suppressants like dextromethorphan; expectorants like guiafenesin; anticholinergics like cyclopentolate and tropicamide; and β-adrenergic receptor agonists like isoprenaline (isoproterenol). It is used in combination with antihistamines and analgesics in cough and cold preparations, with anticholinergics in ophthalmic formulations, and with β-adrenergic receptor agonists in inhalational forms. Intravenous phenylephrine is always formulated by itself. ==Contraindications==

Phenylephrine is contraindicated in people with hypertension, hyperthyroidism, and heart disease due to its vasoconstrictor effects. Relative contraindications include people with Raynaud's syndrome due to vasoconstriction, those taking monoamine oxidase inhibitors (MAOIs) due to inhibition of the metabolism of phenylephrine, and people with prostate problems due to potential exacerbation of urinary retention. == Side effects ==

Phenylephrine taken orally at indicated doses is usually well-tolerated. The low concentration eye drops do not cause blood pressure changes and the changes with the higher dose drops do not last long. The cardiovascular effects of phenylephrine may be potentiated in people with hypertension. People with a history of anxiety or panic disorders, or on anticonvulsant medication for epilepsy, should not take this substance. The drug interaction might produce seizures. Some patients have been shown to have an upset stomach, severe abdominal cramping, and vomiting issues connected to taking this drug. Phenylephrine is pregnancy category C. Due to the lack of studies done in animals and humans, it is unknown whether there is harm to the fetus. Phenylephrine should only be given to pregnant women who have a clear need. == Interactions ==

Phenylephrine is susceptible to metabolism by monoamine oxidase. Because of this, monoamine oxidase inhibitors (MAOIs) can inhibit the metabolism of phenylephrine and increase exposure to the medication. Concomitant use of phenylephrine with the preceding agents may necessitate dose adjustments. Acetaminophen (paracetamol) has been found to increase exposure to oral phenylephrine. It more than doubles phenylephrine's bioavailability, reduces its absorption half-time by 50%, increases phenylephrine levels by approximately 2-fold, and increases peak phenylephrine levels by 4-fold, with substantial interindividual variability. Phenylephrine is widely formulated with acetaminophen in combination products. The combination may increase the cardiovascular effects of phenylephrine. The mechanism of the interaction between phenylephrine and acetaminophen is unknown, but it has been suggested that it may be due to saturation of sulfation pathways by acetaminophen that also participates in phenylephrine metabolism. == Pharmacology ==

Pharmacodynamics Phenylephrine is a selective agonist of the α1-adrenergic receptor, one of the biological targets of the catecholamine hormones and neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline). The drug has weak, minimal, or no agonist activity at the α2-adrenergic receptor or the β-adrenergic receptors. This might help to explain certain unexpected pharmacodynamic effects of the drug. and produces both venous and arterial vasoconstriction. Because of extensive first-pass metabolism, phenylephrine has an oral bioavailability of only about 38% relative to intravenous administration. However, another source has stated that the bioavailability of phenylephrine is poorly documented and may actually be as low as 0.003%. Its lack of metabolism by COMT is said to be responsible for its much longer duration of action than related agents like norepinephrine. ==Chemistry==

Phenylephrine is a substituted phenethylamine and can also be referred to structurally as (R)-β,3-dihydroxy-N-methylphenethylamine. It is a chiral compound and is used as the enantiopure (R)-stereoisomer. In contrast to epinephrine and norepinephrine (noradrenaline; 3,4,β-trihydroxyphenethylamine), phenylephrine is not a catecholamine since it does not have two hydroxyl groups on its phenyl ring. However, phenylephrine does not have a methyl group at the α carbon and hence is not an amphetamine itself. Phenylephrine is used medically almost always as the hydrochloride salt. ==History==

Phenylephrine was first patented in 1927 and was first introduced for medical use in 1938. ==Society and culture==

Names Phenylephrine is the generic name of the drug and its , , and , while its and in the case of the hydrochloride salt are phenylephrine hydrochloride. Availability Phenylephrine is available worldwide as a prescription drug in many different formulations. ==Research==

Hair loss Topical phenylephrine has been studied in the treatment of alopecia (hair loss). It has been found to cause contraction of arrector pili muscles (hair erector muscles), thereby increasing the force required to pluck hair and reducing hair shedding during brushing. ==References==