Phenylephrine applications

Lion of action. The largest use of this drug, however, depends on its vasoconstricting action phenylephrine is used extensively as a nasal decongestant due to its ability to constrict the blood vessels in mucous tissue on local application. In one published... 

FIG. 2. Mechanism of phenylephrine (PE)-mediated wave-like [Ca2+] oscillations in the rabbit inferior vena cava. (A) PE-mediated [Ca2+]j oscillations are completely inhibited by 10 fiM cyclopiazonic acid (CPA), but the average [Ca2+ ]j remains elevated. (B) PE-mediated [Ca2+]j oscillations are abolished by 75 /iM 2-aminoethoxydiphenyl borate (2-APB). (C) Application of 10 piM nifedipine (Nif) reduced the frequency of PE-mediated [Ca2+]j oscillations while additional application of SKF96365 (SKF) completely abolished the remaining [Ca2+] oscillations. (D) Application of 100 /iM 2,4-dichlorobenzamil (2,4-DCB) completely inhibited nifedipine-resistant PE-induced [Ca2+]j oscillations and lowered the [Ca2+]j to a level that is slightly higher than baseline. Additional application of SKF96365 returned the [Ca2+]j level to baseline. (Experimental traces reproduced with permission from Lee et al 2001.)... 

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. 

Combining agonists with some local anesthetics greatly prolongs the duration of infiltration nerve block the total dose of local anesthetic (and the probability of toxicity) can therefore be reduced. Epinephrine, 1 200,000, is the favored agent for this application, but norepinephrine, phenylephrine, and other agonists have also been used. Systemic effects on the heart and peripheral vasculature may occur even with local drug administration but are usually minimal. 

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.)... 

Figure 10.6. Effects of adrenergic agonists on the heart rate (A) and the systolic (0) and diastolic ( ) blood pressure in an anesthe-sizeddog. a Absolute values after application of phenylephrine b, c, d, differences relative to time zero after application of the respective drags.

After topical application phenylephrine contracts the iris dilator muscle and smooth muscle of the conjunctival arterioles, causing pupillary dilation and blanching of the... 

In addition to its usual mydriatic effect for diagnostic purposes, phenylephrine has several other clinical uses. The drug can be a valuable aid in breaking posterior synechiae. Application of the 10% solution to the cornea preceded by a topical anesthetic is usually recommended to help break the adhesion. Furthermore, the effectiveness of topical 10% phenylephrine solution is used for peripheral corneal vessel vasoconstriction during LASIK refractive surgery. 

Systemic Effects. Ocular administration of phenylephrine has been reported to induce acute hypertension (see Table 8-2). Sixty patients were studied after three applications of the 10% solution in each eye at 10-minute intervals.Thirty minutes after the last drop, systolic elevations of 10 to 40 mm Hg and diastolic elevations of 10 to 30 mm Hg occurred in all subjects. In each case pulse rate decreased 10 to 20 beats per minute. In contrast to these observations, however, other investigators reported a lack of systemic vasopressor response with the 10% concentration. 

Data collected by the National Registry of Drug-Induced Ocular Side Effects suggest that, in the general population, a group of patients may have certain risk factors for side effects from topical ocular 10% phenylephrine. Of 15 patients with myocardial infercts, 11 died after topical application of 10% phenylephrine. The average age of these patients was 71 years, and nine individuals had a history of cardiovascular disease. 

Systemic reactions to 2.5% phenylephrine after topical ocular application to an intact eye have rarely been reported in adults. However, an acute rise in systolic blood pressure occurred in a 1-year-old child after the instillation of 0.5 ml of 2.5% phenylephrine during nasolacrimal duct probing. 

The threshold dosage of phenylephrine in the average adult has been estimated to be 0.4 mg intravenously, 2 mg subcutaneously, and 50 mg orally. The upper limit for safe dosage in normal adults is approximately 1.5 mg intravenously and 300 mg subcutaneously. Because a 50-ml drop of 10% phenylephrine contains 5 mg of drug, multiple applications can result in overdosage, especially if absorption from the site of administration is enhanced or if the patient is compromised by age, body size, use of concomitant medications, or trauma. Furthermore, the extent of the absorption into the systemic circulation of topically applied phenylephrine is unknown because absorption has been shown to be possibly diminished due to local vasoconstriction. 

The synthetic adrenergic agonists—phenylephrine, naphazoline, oxymetazoline, and tetrahydrozoline—are available as ocular decongestants (Table 13-2). After topical application to the eye, constriction of conjimcti-val blood vessels occurs at drug concentration levels that generally do not cause pupillary dilation. These agents provide only palliative therapy, because they have no effect on the conjimctival response to antigen. 

To facilitate the application of mydriatics in neonates and infants, a single-instillation solution may be prepared by combining 3.75 ml cyclopentolate 2% with 7.5 ml tropicamide 1% and 3.75 ml phenylephrine 10%.The final solution contains 0.5% cyclopentolate, 0.5% tropicamide, and 2.5% phenylephrine.This combination produces no major side effects and provides an effective pupillary dilation. Alternatively, equal amounts of 1% tropicamide and 2.5% phenylephrine may be mixed together to yield a single combination solution with final concentrations of 0.5% tropicamide and 1.25% phenylephrine. This too should produce adequate pupillary dilation with no major side effects. Again, these solutions can also be applied as a spray. Cyclopentolate, tropicamide, and phenylephrine administered in microdrops (mean drop volume, 5.6 micro liters, as opposed to commercially available standard drops) have the same efficacy with a decreased risk for systemic side effects. 

Figure 20-9 Sector dilation technique using cotton-tipped applicator held at inferior limbus. Phenylephrine-moistened swab is applied for approximately 20 seconds.

In patients who are predisposed to adverse cardiovascular events, the use of tropicamide either alone or in combination with 2.5% phenylephrine provides satisfactory mydriasis while minimizing the risks of systemic complications. In addition, the use of low concentrations of drug, single applications, eyelid closure, and nasolacrimal occlusion minimizes adverse reactions in susceptible patients. Thus the combination solution made by mixing equal amounts of 1% tropicamide and 2.5% phenylephrine as previously described may have the added benefit of reducing the chances of an adverse reaction even further. 

Phenylephrine is seldom given systemically but is still commonly used as a mydriatic for both diagnostic and therapeutic purposes. Ocular application of phenylephrine 10% in pledget form is used to produce hemostasis in laser-assisted in-situ keratomileusis (LASIK) surgery and other ophthalmic surgical procedures. Phenylephrine is in some countries available in a non-prescription concentration of 0.12% for use as an ocular decongestant. Phenylephrine (up to 10 mg intramuscularly) has similar properties and uses to other alpha-adrenoceptor agonists. 

With phenylephrine, several cases of allergic blepharoconjunctivitis have been seen, even at low concentrations the reaction begins 3-4 hours after drug application, persists for 12 hours, and regresses gradually within 72 hours... 

A 62-year-old man developed contact dermatitis after using phenylephrine eye-drops (Neosynerphin POS) (11). The inflammation affected both eyehds symmetrically and resolved rapidly on withdrawal of the eye-drops and application of topical glucocorticoids. Skintesting confirmed hypersensitivity to phenylephrine but no cross-sensitization to ephedrine or adrenahne. 

Phenylephrine was the drug that most often caused sensitization in patients with contact allergy after the application of mydriatic eye-drops. Since several eye-drops are often used in the same patient, it is always important to find out which drug or preservative is the allergen (10-13). 

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. 

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