Phenylephrine pharmacology

This synthetic drug has both chemical and pharmacological similarities to norepinephrine. A characteristic quality of phenylephrine is the distinctly expressed selectivity to a-adrenoreceptors, especially aj-adrenoreceptors. Although phenylephrine increases the contractibility of blood vessels, in practical terms it is not considered a cardiostimulant. 

Pharmacokinetics Phenylephrine is irregularly absorbed from and readily metabolized in the GI tract. After IV administration, a pressor effect occurs almost immediately and persists for 15-20 minutes. After IM administration, a pressor effect occurs within 10-15 minutes and persists for 50 minutes to 1 hour. After oral inhalation of phenylephrine in combination with isoproterenol, pulmonary effects occur within a few minutes and persist for about 3 hours. The pharmacologic effects of phenylephrine are terminated at least partially bythe uptake of the drug into the tissues. Phenylephrine is metabolized in the liver and intestine by the enzyme monoamine oxidase (MAO). The metabolites and their route and rate of excretion have not been identified. 

Methoxamine acts pharmacologically like phenylephrine, since it is predominantly a direct-acting o -receptor agonist. It may cause a prolonged increase in blood pressure due to vasoconstriction it also causes a vagally mediated bradycardia. Methoxamine is available for parenteral use, but clinical applications are rare and limited to hypotensive states. 

Phenylephrine is an effective mydriatic agent frequently used to facilitate examination of the retina. It is also a useful decongestant for minor allergic hyperemia and itching of the conjunctival membranes. Sympathomimetics administered as ophthalmic drops are also useful in localizing the lesion in Horner s syndrome. (See An Application of Basic Pharmacology to a Clinical Problem.)... 

Phenylephrine is a synthetic sympathomimetic amine structurally similar to epinephrine. It acts primarily on ai receptors and has little or no effect on (3 receptors. A minor part of its pharmacologic effects may be attributed to release of norepinephrine from adrenergic nerve terminals. 

A 38-year-old white man with a history of coronary artery disease, myocardial infarction, coronary artery by-pass, alcoholism, and depression took a combined massive overdose of diltiazem and atenolol (24). He underwent cardiopulmonary resuscitation because of cardiac arrest bradycardia, hypotension, and oliguria followed and were resistant to intravenous pacing and multiple pharmacological interventions, including intravenous fluids, calcium, dopamine, dobutamine, adrenaline, prenalterol, and glucagon. Adequate mean arterial pressure and urine output were restored only after the addition of phenylephrine and transvenous pacing. He survived despite myocardial infarction and pneumonia. 

Phenylephrine is a selective ai adrenergic agonist, with a pharmacological structure similar to norepinephrine (noradrenaline), which causes peripheral vasoconstriction. Stimulation of adrenoceptors in the myocardium has an inotropic effect. However, phenylephrine produced no increase in cardiac output, increased systemic vascular resistance and mean arterial pressure and reduced muscle blood flow in anaesthetized horses (Lee et al 1998). Phenylephrine should be reserved for critical conditions where the perfusion of essential organs is compromised and inotropes are not effectively maintaining organ function. The recommended infusion rates are shown in Table 12.3. 

Phenylephrine is a sympathomimetic aj adrenoceptor agonist capable of producing mydriasis in some species by iris dilator muscle contraction. In the horse, topical application of a 10% solution has been shown to have no effect on the pupil diameter in the normal eye. However, 10% phenylephrine in combination with topical atropine is reported to be useful in reversing pupillary spasm in some stubborn cases of anterior uveitis, although there is no pharmacological evidence to support any additive mydriatic effect when the two agents are used together. 

Gregory JS, Bonflglio ME, Dasta JE, et al. Experience with phenylephrine as a component of the pharmacologic support of septic shock. Crit Care Med 1991 19 1395-1400. 

Self-expanding and balloon-expandable stents Resheathable (closed-cell) stents. Solitaire, Trevo, Re Vase Pharmacological vasopressors (e.g., phenylephrine) Mechanical NeuroFlo... 

Although hepatic metabolism continues to be the most important route of metabolism tor xenobiotics, the ability of the liver and intestine to metabolize substances to either pharmacologically inactive or bioactive metabolites before reaching systemic blood levels is called prehepatic or presystemic first pass metabolism, which results in the low systemic availability tor susceptible drugs. Sulfation and glucuronidation are major pathways of presystemic intestinal first-pass metabolism in humans tor acetaminophen, phenylephrine, terbutaline, albuterol, tenoterol, and isoproterenol. 

The manufacturer recommends caution when atomoxetine is given concurrently with other drugs that affect noradrenaline, because of the potential for additive or synergistic pharmacological effects. Examples they name are antidepressants such as imipramine, venlafaxine and mirtaza-pine, and the decongestants pseudoephedrine or phenylephrine. Until more is known, this would seem a sensible precaution. 

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