Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions.
To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.
Togna
G I
GI
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Italy. giuseppina.togna@uniroma1.it
Togna
A R
AR
Caprino
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D001081:Apyrase / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D001398:Aztreonam / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002442:Ceftazidime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000900:Anti-Bacterial Agents; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D002443:Ceftriaxone; D003094:Collagen; D002442:Ceftazidime; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D001081:Apyrase; D001398:Aztreonam