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Titolo:
A FRESH LOOK AT THE MOLECULAR PHARMACOLOGY OF PLASMINOGEN ACTIVATORS - FROM THEORY TO TEST-TUBE TO CLINICAL OUTCOMES
Autore:
SMALLING RW;
Indirizzi:
HERMANN HOSP,6431 FANNIN,ROOM 1246 MSB HOUSTON TX 77030 UNIV TEXAS,SCH MED HOUSTON TX 00000
Titolo Testata:
American journal of health-system pharmacy
, volume: 54, anno: 1997, supplemento:, 1
pagine: 17 - 22
SICI:
1079-2082(1997)54:<17:AFLATM>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; CORONARY THROMBOLYSIS; RANDOMIZED TRIAL; CANINE MODEL; DOUBLE-BOLUS; TIMI TRIAL; BM 06.022; PHASE-I; BM-06.022;
Keywords:
ALTEPLASE; MECHANISM OF ACTION; N-PA; RETEPLASE; THROMBOLYTIC AGENTS; TNK-T-PA;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
R.W. Smalling, "A FRESH LOOK AT THE MOLECULAR PHARMACOLOGY OF PLASMINOGEN ACTIVATORS - FROM THEORY TO TEST-TUBE TO CLINICAL OUTCOMES", American journal of health-system pharmacy, 54, 1997, pp. 17-22

Abstract

The molecular pharmacology of plasminogen activators and its implications for thrombolytic therapy are discussed. The benefits of coronary thrombolysis were first demonstrated with intracoronary and i.v. streptokinase. Tissue plasminogen activator (t-PA) or recombinant t-PA (alteplase) proved to be superior to streptokinase with respect to speed of reperfusion and reperfusion efficacy. Since alteplase neither lessened the risk of bleeding found with streptokinase nor generated Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow rates above about 50%, the quest for faster-acting, safer, and more effective thrombolytic agents has continued. The ideal agent would be highly efficient at converting plasminogen to plasmin, have an intermediate half-life, havea low affinity for fibrin, and be of reasonable cost. Genetic engineering of the wild-type t-PA molecule resulted in reteplase, which has alonger half-life than alteplase and may be superior in terms of lyticactivity, myocardial salvage, and survival. Also under investigation are TNK-t-PA and n-PA, which have longer half-lives and, in animal models, seem to produce more rapid and complete thrombolysis, at less risk of intracranial bleeding, than alteplase. The risk of intracranial bleeding remains a problem with all thrombolytics; the risk versus the benefit will have to be assessed in large randomized trials. An understanding of the functions of various regions of the t-PA molecule has led to genetic engineering of new and promising plasminogen activators.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 18:39:15