Penicillin induced human platelet dysfunction and its reversal by epinephrine.
Antibiotics administered orally can impair platelet function and cause a bleeding diathesis. Platelet function impairment induced by antibiotics such as penicillin, carbenicillin and tetracycline could be corrected by exposing the refractory platelets to epinephrine first and then challenging with other agonists. Penicillin used in this study inhibited the platelet aggregation response and release reaction without blocking the ability of these platelets to convert arachidonic acid to thromboxane. The thromboxane generated in the presence of penicillin could not activate the platelets when threshold concentrations of arachidonate was used as stimulus. Epinephrine stimulation restored the platelet membrane sensitivity and normalized the platelet response to the action of agonists. These studies demonstrate that both by in vitro as well as in vivo routes penicillin induced temporary impairment of platelet function. The refractoriness was not due to the interference of membrane receptors for various agonists or due to the depletion of serotonin, adenine nucleotides or inhibition of cyclooxygenase activity. Penicillin inhibits some essential mechanism involved in platelet activation by agonists and this process may be calcium dependent. Epinephrine through alpha adrenergic stimulation restores the mechanism by which agonists initiate platelet activation.
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D066298:In Vitro Techniques; D010406:Penicillins / Q000009:adverse effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D010406:Penicillins; D011942:Receptors, Adrenergic, alpha; D011451:Prostaglandin-Endoperoxide Synthases; D004837:Epinephrine