Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Abstract

The present study was designed to investigate the effects of salicylate on the antiplatelet action of acetylsalicylic acid as well as on in vivo prostanoid formation and platelet function in healthy volunteers. In the first study six female volunteers received 350 mg acetylsalicylic acid intravenously, with and without previous oral administration of sodium salicylate (1200 mg daily for 3 days). Urinary prostanoid excretion as well as platelet aggregation and thromboxane formation were measured before and during salicylate and after acetylsalicylic acid. In the second study seven female volunteers received sodium salicylate (52.6 mg kg‐1) or acetylsalicylic acid (60.7 mg kg‐1) for 8 days in a randomized cross‐over protocol. Urinary prostanoid excretion, platelet aggregation and thromboxane formation as well as salicylate plasma concentrations were determined before, during and after administration of each drug. Sodium salicylate did not impair the complete suppression of arachidonic acid‐induced platelet thromboxane formation and aggregation obtained by the single intravenous dose of acetylsalicylic acid in the first study. Sodium salicylate in the second study did not affect urinary excretion of prostaglandin E2, its major urinary metabolite (7 alpha‐hydroxy‐5,11‐ diketo‐tetranor‐prostane‐1,16‐dioic acid), and 2,3‐dinor‐6‐keto‐ prostaglandin F1 alpha, the main urinary metabolite of epoprostenol (prostacyclin, PGI2). In contrast, acetylsalicylic acid significantly decreased excretion rates of these prostanoids by 64, 59 and 61%, respectively. In both studies platelet aggregation and thromboxane formation induced by collagen, thrombin or arachidonic acid were not significantly affected by salicylate administration, whereas acetylsalicylic acid inhibited platelet aggregation induced by all three agents as well as thrombin‐ and arachidonic acid induced thromboxane formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Intravenous Aspirin on Prostaglandin Synthesis and Kidney Function in Intensive Care Patients

“…As ASA acetylates cyclo-oxygenase irreversibly [7,8], and as its metabolite salicylic acid does not inhibit prostaglandin synthesis in oral doses up to 1.2 g t.i.d. [32], it can be inferred that the gradual recovery of PGE 2 excretion in our study reflects resynthesis of medullary cyclo-oxygenase.…”

Effects of acetylsalicylic acid and paracetamol alone and in combination on prostanoid synthesis in man.

“…Moreover, recently several cases have been documented in which these drugs were thought to cause acute renal failure (Kleinknecht et al, 1986). In vivo studies have shown that ASA reduces renal cyclooxygenase (Rosenkranz et al, 1986), however, the findings with paracetamol are controversial. In vitro paracetamol can cause inhibition of cyclooxygenase of sheep seminal vesicles (Flower, 1974) and in mice tissues (Brune & Peskar, 1980), albeit at relatively high concentrations.…”

“…While it has been well recognized that ASA inhibits cyclooxygenase in therapeutic concentrations in man (Rosenkranz et al, 1986), there is uncertainty concerning paracetamol. In vitro investigations have shown that paracetamol in concentrations of 5 mm inhibited rat renal medullary slice conversion of exogenous arachidonic acid to PGE2 (Mattamal et al, 1979;Zenser et al, 1978).…”

Mechanisms of Non-Opioid Analgesics Beyond Cyclooxygenase Enzyme Inhibition

“…However, observations dissociating the analgesic and the anti-inflammatory activities of non-opioids have also been reported. At analgesic doses, sodium salicylate does not inhibit urinary excretion of PGE 2 or PGI 2 metabolites in human volunteers [5]. Furthermore, though the COX inhibitory activities of salicylate and acetylsalicylic acid (ASA; aspirin) differs markedly [6], they show similar antiinflammatory potencies [7].…”