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  • Expert opinion on tilarginine in the treatment of shock

    Author(s)
    Howes, Laurence Guy
    Brillante, Divina Gracila
    Griffith University Author(s)
    Howes, Laurence G.
    Year published
    2008
    Metadata
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    Abstract
    Tilarginine is l-N-monomethyl arginine (l-NMMA) or N(G)-monomethyl-l-arginine HCL, a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. l-NMMA therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg ...
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    Tilarginine is l-N-monomethyl arginine (l-NMMA) or N(G)-monomethyl-l-arginine HCL, a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. l-NMMA therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in septic shock whereas the effects of a lower dose (1 mg/(kg h)) in cardiogenic shock complicating myocardial infarction were neutral. The excess mortality in patients with septic shock was almost certainly the result of unfavourable haemodynamic changes induced by l-NMMA (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue oxygen delivery) whereas the lack of benefit in patients with cardiogenic shock complicating myocardial infarction may have been because the dose of l-NMMA was too low. Further studies of l-NMMA at doses < 5 mg/(kg h) in conjunction with inotrope support may produce more beneficial results. Conversely, the use of a selective inducible NOS inhibitor to reduce the pathological effects of excessive NO production although leaving the beneficial effects of vascular NO production by endothelial NOS unaltered may prove to be of value.
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    Journal Title
    Expert Opinion on Investigational Drugs
    Volume
    17
    Issue
    10
    Publisher URI
    http://informahealthcare.com/
    DOI
    https://doi.org/10.1517/13543784.17.10.1573
    Subject
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/22385
    Collection
    • Journal articles

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