Pharmacotherapy of acute respiratory distress syndrome.

To date, the only therapeutic option that has convincingly been shown to decrease mortality in acute respiratory distress syndrome (ARDS) has been to use a lung-protective strategy that minimises the iatrogenic consequences of providing adequate life support through the use of mechanical ventilation. In terms of the pharmacological options for ARDS, no single drug or treatment has been shown to be the magic bullet in this disease. The search for novel therapies and pharmacological agents is active and relentless. Important pathophysiological areas of focus are preventative therapy, supportive care and treatment of the underlying inflammatory process. In this paper we will review current and experimental approaches to the management of ARDS. In addition, the pathophysiological basis for their putative modes of action, the current state of the literature and the potential for future clinical development will be discussed.

Effects of aspirin on platelet aggregation in smokers and nonsmokers.

OBJECTIVE: To assess the relative antiaggregatory ability of aspirin on platelets of smoking and nonsmoking healthy volunteers. DESIGN: Prospective, randomized, crossover study. SETTING: Tertiary-care teaching institution. SUBJECTS: Eighteen healthy smoking and nonsmoking male volunteers. INTERVENTIONS: Each subject received aspirin 325 mg or ticlopidine 250 mg bid as an active control for 7 days in a crossover manner separated by a 1-month washout period. Whole blood platelet aggregation was measured on four occasions, twice at baseline and once after each drug treatment. OUTCOME MEASUREMENT: Whole blood ex vivo platelet aggregation in terms of impedance (omega) and adenosine triphosphate (ATP) release (nmol), as assessed using Lumi-aggregometry. RESULTS: Aspirin was associated with significantly less ATP release in both smokers (p = 0.01) and nonsmokers (p = 0.003). No significant differences in platelet aggregation were found between smokers and nonsmokers at baseline or with any treatment phases. Sixty-seven percent and 17% of volunteers receiving ticlopidine and aspirin, respectively, reported adverse effects. CONCLUSIONS: Twice-daily administration of aspirin for 7 days to healthy volunteers was well tolerated and also reduced platelet aggregation significantly regardless of smoking status.

Quinupristin/dalfopristin (RP 59500): a new streptogramin antibiotic.

OBJECTIVE: To review the current knowledge on RP 59500 (quinupristin/dalfopristin, Synercid), a new streptogramin antibiotic, with respect to its pharmacology, pharmacokinetics, pharmacodynamics, mechanism of resistance, and in vitro inhibitory and bactericidal activity. DATA SOURCES: A MEDLINE search using keywords RP 59500, pristinamycin, virginiamycin, and streptogramin was performed. Relevant abstracts presented at recent scientific conferences also were consulted. STUDY SELECTION: Because RP 59500 is a relatively new investigational agent, relevant in vitro and animal studies were selected. All available human studies were included as well. DATA EXTRACTION: Data from in vitro and in vivo studies were included, with particular emphasis on human studies. DATA SYNTHESIS: RP 59500 is a new injectable streptogramin antibiotic consisting of a mixture o 2 synergistic pristinamycin compounds. RP 59500 possesses in vitro inhibitory and bactericidal activity against most isolates of gram-positive organisms including vancomycin-resistant Enterococcus faecium, selected gram-negative bacteria, and most anaerobic organisms. Based on preliminary data, the drug appears to be metabolized rapidly and extensively while exhibiting a significant postantibiotic effect. Data from ongoing clinical trials suggests that RP 59500 is well-tolerated except for mild injection site irritations. However, before the role of RP 59500 within the vast armamentarium of antimicrobials can be elucidated, additional studies need to be conducted to document its clinical efficacy. CONCLUSIONS: Based on in vitro susceptibility testing, in vivo studies, and preliminary clinical data, RP 59500 may be an alternative to the glycopeptides, especially for inherently resistant organisms. Further studies are needed to confirm this agent's in vitro activity and to establish its clinical efficacy.