Phenylephrine vascular effects

Phenylephrine is a fast-acting, short-duration a, agonist. Phenylephrine has primarily vascular effects, and does not impair cardiac or renal function. Phenylephrine is useful when tachycardia limits the use of other vasopressors.24,27-28... 

Despite its purported use in refractory septic shock, very little information is published regarding the clinical efficacy of phenylephrine. Nevertheless, it is an attractive agent for use in sepsis owing to its selective a-agonism and primarily vascular effects and its rapid onset < and short duration of action. It is generally initiated at dosages of 0.5 mcg/kg per minute and may be titrated quickly to desired effect. 

A large number of diugs interfere with the smooth muscle contraction. These compounds lower blood pressure and are referred to as antihypertensive. In this section, only those coumpounds will be mentioned that have a direct effect on smooth muscle tone. Phenylephrine is an agonist on most smooth muscles and activates ax adrenoceptors. Carbachol is an agonist on some smooth muscles and activates contraction through muscarinic receptors. Blockers of the ax-adrenoceptors such as prazosin and urapidil are competitive inhibitors of the ax-receptor in vascular and bladder smooth muscle. Phenoxybenzamine is an ineversible blocker of ax receptors and phentol-amine blocks ax and a2 receptors. Ca2+ channel blockers such as the dihydropyiidines, phenylalkyla-mines and benzothiazepines lower smooth muscle tone by blocking the L-type calcium channel. 

Carvedilol also (1) attenuates the pressor effects of phenylephrine, (2) causes vasodilation, and (3) reduces peripheral vascular resistance. These effects contribute to the reduction of blood pressure and usually are seen within 30 minutes of drug administration. 

Alpha receptors are widely expressed in vascular beds, and their activation leads to arterial and venoconstriction. Their direct effect on cardiac function is of relatively less importance. A relatively pure agonist such as phenylephrine increases peripheral arterial resistance and decreases venous capacitance. The enhanced arterial resistance usually leads to a dose-dependent rise in blood pressure (Figure 9-... 

Recently, Tsubosaka et al. (2010a) reported that halichlorine was also revealed to inhibit L-type Ca2+ channels, which leads to inhibit smooth muscle contraction. In their report, the direct effect of halichlorine on vascular contractility was investigated. Then, halichlorine was found to inhibit both high concentration of K+- and phenylephrine-induced contractions in rat aorta dose dependently. The effect of halichlorine on high K+-induced contraction was shown to be stronger than that on phenylephrine-induced contraction. Because known L-type Ca2+ channel blockers, verapamil and nifedipine, were observed to show the similar effect by them, it was suggested that halichlorine selectively inhibits L-type Ca2+ channels. Then, the effect of halichlorine on intracellular Ca2+ concentration in vascular smooth muscle tissue was examined using a fluorescent Ca2+ indicator, Fura-2. 

In newborn infants the benefit of accurate assessment of gestational age by examination of the anterior vascular capsule of the lens and the value of funduscopic examination in ill premature babies must be weighed against the possible risks of the associated increase in blood pressure produced by the pupillary dilators. Since there is no increase in mydriatic effect with repeated instillation or increasing concentration, and their small body mass places premature neonates at increased risk of phenylephrine overdose, it is prudent to use the lowest possible concentration, as well as the most effective combination of mydriatics for indirect ophthalmoscopy in premature infants when such examination is absolutely necessary. The hypertensive effect is likely to be maximal at some time within the first 20 minutes, and whenever possible (or when risk factors are present) the blood pressure should be monitored. 

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. 

Martin etal. (2002) also found that (+)-kavain (10 —10 M) dose-dependently relaxed isolated rat aortic ring preparations that had previously been contracted with phenylephrine (PE), as an effect not dependent on functional epithelium. In addition, kavain pretreatment attenuated muscle contraction evoked by PE. However, PE elicited contraction in Ca free buffer was not affected by kavain, suggesting that intracellular signaling mechanisms probably were not involved. In rings pretreated with the L-type Ca channel blocker nifedipine, kavain mediated relaxation was appreciably attenuated. Further, muscles selectively contracted with Bay K 8644, an L-type Ca channel activator, were dose-dependently relaxed by kavain. The findings suggest that kavain impairs vascular smooth muscle contraction probably through inhibition of Ca ion channels. 

Phenylephrine is indicated in the treatment of vascular failure in shock, shock-like states, drug-induced hypotension, or hypersensitivity to overcome paroxysmal supraventricular tachycardia to prolong spinal anesthesia as a vasoconstrictor in regional analgesia and to maintain an adequate level of BP during spinal and inhalation anesthesia. Phenylephrine is a powerful postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart (see also Figure 39). 

In 19 healthy parturients undergoing elective cesarean section who were to phenylephrine or ephedrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure fell by more than 10 mmHg, both the vasopressors restored maternal arterial pressure effectively [25 J. Ephedrine had no significant effects on Doppler velocimetry but phenylephrine infusion significantly increased the blood flow velocity waveform indices in the uterine and placental arcuate arteries and reduced vascular resistance significantly in the fetal renal arteries. However, healthy... 

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