Dose-dependent Inhibition of Platelet Function by Acetaminophen in Healthy Volunteers

Munsterhjelm, E.; Munsterhjelm, Nina M.; Niemi, Tomi; Ylikorkala, Olavi; Neuvonen, Pertti J.; Rosenberg, P. H.

doi:10.1097/00000542-200510000-00009

Cited by 64 publications

(54 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the cold pressor test, the analgesic effect of oral paracetamol 1 g has been detected in three studies [19,34,35], but in another study, 30 mg/kg i.v. did not produce any analgesia [36]. Pain evoked by laser skin stimulation was sensitive to oral paracetamol, probably due to skin inflammation caused by repeated laser pulses [37,38].…”

Section: Discussionmentioning

confidence: 86%

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Tiippana

Hamunen

Kontinen

et al. 2012

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Experimental studies suggest that paracetamol-induced analgesia is mediated via central serotonergic pathways and attenuated by 5-HT3-antagonists. However, clinical studies do not support this, and 5-HT3-antagonists are expected to reduce pain by blocking the descending pronociceptive pathway. The current project tested whether tropisetron attenuates analgesia by paracetamol. Two randomized, double-blind, crossover studies with 18 healthy male volunteers in each were performed. Pain stimuli were cold water immersion (cold pressor test), contact heat pain (study 1) and electrical stimulation (study 2). In both studies, tropisetron 5 mg i.v. or saline was administered, followed by paracetamol 2 g i.v. 30 min. later. Individual changes in heat and cold pain intensity, cold pain tolerance and unpleasantness were recorded. The same thresholds were also expressed as scores (% of the individual score at baseline). Additionally, previously published findings on the effects of paracetamol and its interaction with 5HT3-antagonists in human experimental pain models were reviewed. After calculation of the sensory and pain scores (%), tropisetron seemed to amplify the analgesic action of paracetamol. Paracetamol 2 g i.v. did not show any statistically significant analgesia in thermal tests (study 1), or differences in sensory, pain detection or moderate pain thresholds of the electrical stimulus (study 2). As paracetamol did not have a measurable analgesic effect in these tests, no conclusions can be drawn about the interaction between paracetamol and tropisetron. However, tropisetron may have an analgesic effect of its own. Clinicians should not avoid using these drugs together, unless larger clinical studies indicate otherwise.

show abstract

Section: Discussionmentioning

confidence: 86%

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Tiippana

Hamunen

Kontinen

et al. 2012

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…In contrast, in a model of tissue injury with chronic inflammation, acetaminophen suppressed PGE 2 formation without inhibiting TXB 2 release, suggesting that acetaminophen is a selective COX-2 inhibitor in vivo when the COX-2 gene is upregulated in inflammation [19] . It has also been reported that acetaminophen in combination with an NSAID may augment COX inhibition [64,65] . The present data with acetaminophen are in agreement with observations in humans that acetaminophen had no consistent effect on arachidonic acid metabolism [66] .…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen, Phenacetin and Dipyrone Do Not Modulate Pressor Responses to Arachidonic Acid or to Pressor Agents

Nossaman

Baber²,

Nazim³

et al. 2007

Pharmacology

View full text Add to dashboard Cite

In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), the nonopioid analgesics phenacetin, acetaminophen and dipyrone exhibit weak anti-inflammatory properties. An explanation for this difference in pharmacologic activity was provided by the recent discovery of a new cyclooxygenase isoform, cyclooxygenase (COX)-3, that is reported to be inhibited by phenacetin, acetaminophen and dipyrone. However, COX-3 was found to be a spliced variant of COX-1 and renamed COX-1b. Although recent studies provide evidence for the existence of this new COX isoform, it is uncertain whether this COX-3 (COX-1b) isoform, or putative acetaminophen-sensitive pathway, plays a role in the generation of vasoactive prostaglandins. NSAIDs increase systemic blood pressure by inhibiting the formation of vasodilator prostanoids. Angiotensin II, norepinephrine and other vasoconstrictor agents have been reported to release prostaglandins. It is possible that this acetaminophen-sensitive pathway also modulates pressor responses to these vasoconstrictor agents. Therefore, the purpose of the present study was to determine whether this acetaminophen-sensitive pathway plays a role in the generation of vasoactive products of arachidonic acid or in the modulation of vasoconstrictor responses in the pulmonary and systemic vascular bed of the intact-chest rat. In the present study, the nonopioid analgesics did not attenuate changes in pulmonary or systemic arterial pressure in response to injections of the prostanoid precursor, arachidonic acid, to the thromboxane A₂ mimic, U46619, or to angiotensin II or norepinephrine. The results of the present study do not provide evidence in support of a role of a functional COX-3 (COX-1b) isoform, or an acetaminophen-sensitive pathway, in the generation of vasoactive prostanoids or in the modulation of responses to vasoconstrictor hormones in the intact-chest rat.

show abstract

“…Inhibition is observed after a standard dose of 15 mg.kg )1 [24], but the degree of inhibition is significantly less than is seen with NSAIDs such as diclofenac [54], and surgical bleeding attributable to paracetamol is unlikely.…”

Section: Adverse Effects and Toxicitymentioning

confidence: 94%

“…Paracetamol inhibits both isoforms of cyclo-oxygenase (COX); the constitutive COX-1, and the inducible COX-2. Non-steroidal anti-inflammatory drugs (NSAIDs) also act by inhibition of COX, yet important differences exist; notably, paracetamol displays weak antiinflammatory activity, few or no gastrointestinal side effects, and only a small dose-dependent alteration of platelet function [23,24]. In 2002, a COX-1 splice variant, COX-1b (later termed COX-3) was cloned from canine cerebral cortex [25].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Paracetamol has recently been shown to have a dosedependent anti-aggregatory effect on platelets, mediated through inhibition of platelet COX-1 and subsequent decreased synthesis of thromboxane A 2 [24,53]. Inhibition is observed after a standard dose of 15 mg.kg )1 [24], but the degree of inhibition is significantly less than is seen with NSAIDs such as diclofenac [54], and surgical bleeding attributable to paracetamol is unlikely.…”

Section: Adverse Effects and Toxicitymentioning

confidence: 99%

See 1 more Smart Citation

Peri‐operative use of paracetamol

2008

View full text Add to dashboard Cite

show abstract

Dose-dependent Inhibition of Platelet Function by Acetaminophen in Healthy Volunteers

Abstract: Acetaminophen, which is a weak inhibitor of platelet cyclooxygenase 1, has a dose-dependent antiaggregatory effect. This property may become clinically significant in patients with intrinsic or drug-induced impairment of hemostasis.

Cited by 64 publications

References 30 publications

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Acetaminophen, Phenacetin and Dipyrone Do Not Modulate Pressor Responses to Arachidonic Acid or to Pressor Agents

Peri‐operative use of paracetamol

Contact Info

Product

Resources

About