E Munsterhjelm1, T T Niemi, M T Syrjälä, O Ylikorkala, P H Rosenberg. 1. Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, PO Box 340 (P-floor), FIN-00029 HUS, Helsinki, Finland. edward.munsterhjelm@hus.fi
Abstract
BACKGROUND:Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. METHODS:Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test. RESULTS: Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. CONCLUSIONS: The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.
RCT Entities:
BACKGROUND:Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. METHODS: Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test. RESULTS: Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. CONCLUSIONS: The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.
Authors: Garry G Graham; Michael J Davies; Richard O Day; Anthoulla Mohamudally; Kieran F Scott Journal: Inflammopharmacology Date: 2013-05-30 Impact factor: 4.473