Document Detail


Expert opinion on tilarginine in the treatment of shock.
MedLine Citation:
PMID:  18808317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Laurence Guy Howes; Divina Gracila Brillante
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  17     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-23     Completed Date:  2008-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1573-80     Citation Subset:  IM    
Affiliation:
Griffith University and Bond University Medical Schools, Gold Coast Hospital, Department of Pharmacology and Therapeutics, Nerang St, Southport, Queensland 4215, Australia. laurie_howes@health.qld.gov.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Enzyme Inhibitors / therapeutic use*
Heart / drug effects
Humans
Nitric Oxide / physiology
Nitric Oxide Synthase / antagonists & inhibitors*
Shock, Cardiogenic / drug therapy*
Shock, Septic / drug therapy*
Sympathetic Nervous System / drug effects
omega-N-Methylarginine / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; EC 1.14.13.39/Nitric Oxide Synthase

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