Phenylephrine cardiovascular effects

MVW Bergamini, DL Murray, PD Krause. (1979). Pivalyl phenylephrine (PPE), a mydriatic prodrug of phenylephrine with reduced cardiovascular effects. Invest Ophthalmol Vis Sci 20 187. 

Effects of autonomic blockade on the response to phenylephrine (Phe) in a human subject. Left The cardiovascular effect of the selective K-agonist phenylephrine when given as an intravenous bolus to a subject with intact autonomic baroreflex function. Note that the increase in blood pressure (BP) is associated with a baroreflex-mediated compensatory decrease in heart rate (HR). Right The response in the same subject after autonomic reflexes were abolished by the ganglionic blocker trimethaphan. Note that resting blood pressure is decreased and heart rate is increased by trimethaphan because of sympathetic and parasympathetic withdrawal. In the absence of baroreflex buffering, approximately a tenfold lower dose of phenylephrine is required to produce a similar increase in blood pressure. Note also the lack of compensatory decrease in heart rate. 

The different cardiovascular effects of a- and (3-receptors are illustrated in the experiment in Figure 10.6. Phenylephrine, an a-selective agent, causes vasoconstriction and... 

Cardiovascular Disease. Patients with systemic hypertension, arteriosclerosis, and other cardiovascular diseases may be at risk when high concentrations of topically administered adrenergic agonists such as phenylephrine are used. Repeated topical doses or soaked cotton pledgets placed in the conjunctival sac have been associated with adverse cardiovascular effects. Likewise, P-blockers should be avoided or used cautiously in patients with congestive heart disease, severe bradycardia, and high-grade atrioventricular block. Topical P-blockers, however, may be used safely in patients with cardiac pacemakers. 

Thyroid Disease. Elevated blood pressure or other adverse cardiovascular effects can result when patients with Graves disease receive adrenergic agonists with vasopressor activity. This is due to the increased catecholamine activity associated with hyperthyroidism. The primary agent to be avoided or used cautiously is topically applied phenylephrine for pupillary dilation. 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

Fraunfelder FT, Meyer SM. Possible cardiovascular effects secondary to topical ophthalmic 2.5% phenylephrine. Am J Ophthalmol 1985 99 362-363. 

Because of the premature infent s small body mass and less mature cardiovascular and cerebrovascular status, prudence dictates using the lowest concentration yet the most effective combination of mydriatics for pupillary dilation. A combination of 2.5% phenylephrine and 0.5% to 1.0% tropicamide provides sufficient mydriasis without adverse cardiovascular effects in preterm infents.The use of tropicamide alone, however, does not generally produce a sufficient mydriasis in premature infants. Adding cyclopentolate to the tropicamide regimen improves mydriasis but may contribute to elevated blood pressure and heart rate. Moreover, because of possible gastric secretory inhibition in preterm infants, the concentration of cyclopentolate should be limited to 0.25%. A commercially available combination of 1% phenylephrine and... 

Thomas SH, Clark KL, Allen R, Smith SE. A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies. BrJ Clin Pharmacol 1991 32(6) 705—711. 

The major dired-ading adrenoceptor agonist drugs are described. The alpha agonist phenylephrine increases mean BP, has no effed on pulse pressure, and elicits a reflex bradycardia. Isoproterenol, a beta agonist, decreases mean BP, increases pulse pressure, and causes marked tachycardia. Cardiovascular effects of norepinephrine (NE) are similar to phenylephrine, but it is also a cardiac (i, adrenoceptor j activator. The cardiovascular effects of epinephrine (E) are betalike at low doses and alphalike at high j doses. 

Kumar V, Schoenwald RD, Chien DS, Packer AJ, Choi WW. Systemic absorption and cardiovascular effects of phenylephrine eyedrops. Am... 

The anesthetic effect of the agents with short and intermediate durations of action can be prolonged by increasing the dose or adding a vasoconstrictor agent (eg, epinephrine or phenylephrine). The vasoconstrictor slows the removal of the local anesthetic from the injection site. In addition, it decreases the blood level and the probability of cardiovascular and CNS toxicity. 

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. 

Adrenaline (epinephrine) stimulates alpha- and beta-receptors of the cardiovascular system, the former results in vasoconstriction (mainly alphaj) and the latter in both vasodilatation (mainly beta2) and stimulation of the heart (mainly betaj). The net result is usually a modest increase in heart rate and a small rise in blood pressure. However, if the heta-reeeptors are blocked by a non-selective beta blocker, such as propranolol or nadolol (see Table 22.1 , (p.833) for a list), the unopposed alpha vasoeonstrietion causes a marked rise in blood pressure, followed by reflex bradyeardia. Cardioselective beta blockers such as atenolol and metoprolol, whieh are more selective for betaj receptors, do not prevent the vasodilator aetion of adrenaline at beta2 receptors to the same extent, and therefore the effect of any interaction is relatively small. Consequently, adrenaline has been used to assess the degree of beta blockade produced by propranolol and other beta blockers.Phenylephrine is largely an alpha stimulator, therefore beta blockers should have a minimal effect on its action. 

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