Pressor effects

Hydrastinine causes little nervous disturbance except in large doses, when it paralyses the nervous system. The pressor effect is greater than that obtained with hydrastine, because of the increased cardiac efficiency and greater peripheral constrictor action induced by moderate doses. 

Both Cushny and Dale found the amorphous gelsemium alkaloids represented by such fractions as gelseminine much more active than gelsemine. Cushny stated that gelseminine resembled coniine in action and showed a greater depressant effect on the central nervous system, but unlike coniine it exerted no pressor effect. It was also a powerful mydriatic. Dale found that 0-001 gm. of the hydrochlorides of the amorphous alkaloids injected into rabbits caused death from respiratory failure in 25 minutes, preceded by convulsions. These results are explained by the subsequent isolation from such amorphous fractions, of the potent alkaloids sempervirine and gelsemicine. 

Both these predictions are borne out by clinical experience despite the snag that only MAOb is found in serotonergic neurons (Saura et al. 1996). So far, there is no explanation for this anomaly. However, the lack of a tyramine-induced pressor effect with moclobemide probably owes more to the fact that it acts as a reversible inhibitor of MAOa (RIMA) than to its isoenzyme selectivity. Its reversible inhibition of MAOa means that, should tyramine ever accumulate in the periphery, it will displace... 

James, J. E., Richardson, M., Pressor effects of caffeine and cigarette smoking. British Journal of Clinical Psychology 30(3), 276-278, 1991. 

Perry HM, Erlanger MW. 1978. Pressor effects of chronically feeding cadmium and lead together. In Hemphill DD, ed. Trace substances in environmental health. Vol. 12. Columbia, MO University of Missouri-Columbia, 268-275. 

Alles, G.A. The comparative physiological actions of the DL-beta-phenylisopropylamines. I. Pressor effect and toxicity. J. Pharmacol. Exp. Ther. 47 339, 1933. 

The distinctive feature of a-adrenoblockers is their ability to reduce the pressor effect of pharmacological doses of epinephrine (adrenaline). 

Hypotension Hypotension (postural) occurs regularly in about 50% of patients while they are supine, manifested by dizziness, light-headedness, vertigo, or faintness. Tolerance occurs unpredictably but may be present after several days. Hypotension with supine systolic pressure above 75 mm Hg need not be treated unless symptomatic. If supine systolic pressure falls below 75 mm Hg, infuse dopamine or norepinephrine to increase blood pressure use dilute solution and monitor blood pressure closely because pressor effects are enhanced by bretylium. Perform volume expansion with blood or plasma and correct dehydration where appropriate. Transient hypertension and increased frequency of arrhythmias Transient hypertension and increased frequency of arrhythmias may occur due to initial release of norepinephrine from adrenergic postganglionic nerve terminals. 

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. 

The pharmacologic actions of these agents include Alpha-adrenergic stimulation (vasoconstriction, nasal decongestion, pressor effects) - -adrenergic stimulation (increased myocardial contractility and conduction) and 2-adrenergic stimulation (bronchial dilation and vasodilation, enhancement of mucociliary clearance, inhibition... 

Use cautiously in people with acute or chronic respiratory impairment, particularly children, because phenothiazines may suppress the cough reflex. If hypotension occurs, epinephrine is not recommended because phenothiazines may reverse its usual pressor effect and cause a paradoxical further lowering of blood pressure. Because these drugs have an antiemetic action, they may obscure signs of intestinal obstruction, brain tumor, or overdosage of toxic drugs. 

There have been reports of excessive hypotension and paradoxical pressor effects following intravenous administration of labetalol. These latter effects may be due to a labetalol-induced blockade of neuronal amine uptake, which increases the concentrations of norepinephrine in the vicinity of its receptors. 

Because it is stable, desmopressin is preferred for treatments especially if pressor effects are not desired. The primary indication for therapy is central diabetes insipidus, a disorder that results when ADH secretion is reduced and that is characterized by polydipsia, polyuria, and dehydration. Desmopressin is also used to reduce primary nocturnal enuresis, or bedwetting, in children. It is useful in people with mild hemophilia A or with some types of von Willebrand s disease, in which von Willebrand s factor is present at low levels. In these cases, desmopressin is given when excessive bleeding occurs or before surgery to help reduce bleeding indirectly by increasing the amounts of coagulation factors. 

Overdosage may produce extensions of the pharmacologic effects of f he drug. Excessive pressor effect, skeletal muscle hyperactivity tachycardia, and enhanced deep tendon reflexes may be early signs of overdosage. 

Assess the patient for exfravasafion. If exfravasafion occurs, expecf f o infiltrate the affected area with 10 to 15 ml sterile saline containing 5 to 10 mg phentolamine. Know that phentolamine does not alter the pressor effects of norepinephrine... 

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. 

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