[The pharmacology and clinical aspects of the prostanoids].
Prostanoids are derivative of arachidonic acid and arising from a common endoperoxide and they possess multiple and even opposing effects. Their main function is to control haemostasis and to maintain vascular homeostasis. Among these compounds thromboxane, generated by platelets, is a powerful vasoconstrictor and an inducer of platelet aggregation; prostaglandin E1 (PGE1) and prostacyclin (PGI2) are potent vasodilator and inhibitor of platelet aggregation. For these properties PGE1 and PGE2 are object of interest for the potential therapeutical use in treatment of atherosclerotic diseases, where mechanisms of vascular defense are altered and amplified. Pharmacokinetic and pharmacodynamic characteristics of these compound have been per se a good rationale for plenty of experimental studies which generated enthusiasm and hope of new therapeutic means in patients with surgically unreconstructible peripheral arterial disease. Nevertheless clinical trials have to face many difficulties deriving from their properties themselves. PGE1 and PGI2 are unstable hormones with local action and it is difficult to employ them in clinical practice. Moreover their protean action is often implicated in not unusual adverse effects. The development of compounds with a prostacyclin-type of action, but long lasting and therefore easier to handle, undoubtedly facilitated clinical research. But we still lack firm indications for a correct therapeutic use. Limb ischemia is the condition in which prostanoids were mostly studied. Although anecdotal reports or uncontrolled studies provided encouraging results, several controlled trials failed to demonstrate a consistent efficacy of either PGE1 or PGI2, whilst metanalytic review of controlled trials on iloprost demonstrated an efficacy on critical and less severe limb ischemia, thromboangiitis obliterans and Raynaud's phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Ambrosioni
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Clinica Medica III, Policlinico S. Orsola, Università degli Studi di Bologna.
Degli Esposti
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D001157:Arterial Occlusive Diseases / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D011453:Prostaglandins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D011453:Prostaglandins
Farmacologia e clinica dei prostanoidi.