iloprost and piroximone

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 treati

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Alprostadil; Amrinone; Carbazoles; Carvedilol; Enoximone; Female; Humans; Iloprost; Imidazoles; Indoramin; Isosorbide Dinitrate; Labetalol; Milrinone; Molsidomine; Nitroglycerin; Nitroprusside; Oxyfedrine; Pentaerythritol Tetranitrate; Phosphodiesterase Inhibitors; Piperazines; Prazosin; Pregnancy; Propanolamines; Pyridones; Theophylline; Trapidil; Vasodilator Agents

Platelet activity is regulated through synthesis and degradation of the intracellular second messengers cAMP or cGMP. The antiplatelet effect of the phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50 of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of platelet count following injection of 100 micrograms/kg bw collagen was measured after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in washed platelets rose time and dose dependently after PIR. Coincubation of PDE III inhibitor PIR and adenylate cyclase activator Iloprost (ILO) resulted in a significant synergistic enhancement of the antiaggregatory effect. The PDE III inhibitor PIR exerted an effective inhibition of platelet aggregation in vivo and in vitro. The inhibitory effects in vitro were synergistically augmented by the prostacyclin analog Iloprost. These platelet inhibitory effects might be of clinical importance.

Topics: Adenosine Diphosphate; Adenylyl Cyclases; Animals; Collagen; Cyclic AMP; Drug Synergism; Enzyme Activation; Humans; Iloprost; Imidazoles; In Vitro Techniques; Male; Phosphodiesterase Inhibitors; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Rats; Rats, Inbred Strains