Clinical Pharmacokinetics of Vasodilators

Abstract

Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy.

Prednisolone reduces nitric oxide‐induced migraine

“…In contrast, the slowly developing headache (see the placebo curves in Fig. 1) occurs after GTN has disappeared from the blood because GTN has a very short half life of 2.5 min [18]. The delayed headache accordingly, must be a result of induction of some slowly developing process in the cells, most likely by altered gene expression.…”

Sodium nitroglycerin induces middle cerebral artery vasodilatation in young, healthy adults

“…When administered sublingually, this lipid-soluble drug is rapidly absorbed over the mucosal membranes in the mouth (Zhang, Zhang, & Streisand, 2002). Sodium nitroglycerin has a half-life of ∼2.5 min (Kirsten, Nelson, Kirsten, & Heintz, 1998b) and acts as a metabolism-dependent NO donor, amplifying NO production and eliciting subsequent vasodilatory effect(s) (Kirsten et al, 1998b;Kirsten, Nelson, Kirsten, & Heintz, 1998a). Therefore, NTG is viewed as an ideal drug both for clinical use and for studying non-endothelial vasomotor function (Mao et al, 2012).…”

“…A third possible limitation is the time between treatment administrations and the lack of a second baseline measurement before the second treatment. As mentioned, the half-life of NTG in plasma is ∼2.5 min (Kirsten et al, 1998b). Seven half-lives were allowed after the NTG treatment to optimize the loss of drug effects.…”

Welche Medikamente sind in der Stillzeit erlaubt?

“…Bei postpartaler Neueinstellung der Hypertonie mit Urapidil sollte das Stillen unterbrochen werden, da keine pharmakokinetische Daten oder publizierten Erfahrungen zu Urapidil vorliegen [7,8,59]. Falls unter Antihypertensiva-Therapie ein Fortführen des Stillens erwünscht ist, können Labetalol, Dihydralazin, Nifedipin oder Nitroglycerin sicher verabreicht werden [7,8,59,60]. Alpha-Methyldopa ist das Antihypertensivum der ersten Wahl in der Schwangerschaft und kann in der Stillzeit sicher angewandt werden [7].…”