Vasoconstrictor substances, such as norepinephrine and epinephrine, have been mingled with local anesthetics to decrease their toxic effects and to prolong the depth of the anesthesia in clinic. However, some evidences approve that these catecholamines can cause systolic and diastolic hypertension, which increases the potential drug risk. Trying to find a vasoconstrictor without the side effects of the catecholamines, Boisonnas and Guttman synthesized felypressin from antidiuretic hormone. The felypressin is a synthetic vasoconstrictor substance that changes 2 tyrosines of vasopressin to phenylalanine and 8 arginine to lysine, which possesses selective blood pressure booster and hemostatic effect.
This product has no uterine contraction, prolactin and anti-diuretic effects in the range of blood pressure and hemostatic dose. Its coronary vasoconstriction was notable, which was about 5 times as much as that of lysine vasopressin. But the antidiuretic effect is feeble, which was only 1/10 to 1/40 of vasopressin. Its pressor effect is mild with longer maintenance time, which exhibits good compatibility with halothane anesthetics. It does not cause arrhythmias such as ventricular fibrillation when used in combination with epinephrine.
Compared with epinephrine, the vasoconstriction function of felypressin is weaker and slows down in taking effect, but the duration is longer. Moreover, its vasoconstriction is also weaker than epinephrine. So it is not easy to cause hypoxia in local tissues and has no obvious effect on the heart. The greatest advantage of felypressin is its low toxicity and high safety. It is especially suitable for the patients who are prohibited from using using adrenaline; it also can be used for patients with cardiovascular disease, hyperthyroidism, and patients who have previously used monoamine oxidase inhibitor and tricyclic antidepressant.
Pharmacokinetics and metabolism
Felypressin interferes with uterine tension and hinders placental blood circulation, so pregnant women should not use it. Other possible side effects were elevated blood pressure, bradycardia, coronary vasoconstriction, but no myocardial ischemia was found in animal experiments and clinic settings. The usual doses had no significant effects on blood pressure, heart rate and electrocardiogram. The American Drug Safety Committee (DSCD) pointed out that patients with coronary heart disease received 3% procaine treatment, containing 0.03 international units of felypressin per ml, not more than 8. 8 ml, 13 ml in healthy people.
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Fleury, C. A., Andreo, V. C., Lomba, P. C., Dionísio, T. J., Amaral, S. L., Santos, C. F., & Faria, F. A. (2015). Comparison of epinephrine and felypressin pressure effects in 1K1C hypertensive rats treated or not with atenolol. Journal of anesthesia, 29(1), 56-64.
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