The Pharmacokinetics and Analgesic Efficacy of Larger Dose Rectal Acetaminophen (40 mg/kg) in Adults: A Double-Blinded, Randomized Study

Beck, Dieter; Schenk, Michael; Hagemann, Kerstin; Doepfmer, Ulrich R.; Kox, Wolfgang J.

doi:10.1097/00000539-200002000-00035

Cited by 39 publications

(19 citation statements)

References 11 publications

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“…The analgesic efficacy of paracetamol is equivalent to that of aspirin, while its plasma levels required for the analgesic activity are higher than those needed for the antipyretic activity (18).…”

Section: Pharmacological Effectsmentioning

confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB 1 receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB 1 receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB 1 receptor agonist, completely prevents the analgesic ac- 250CNS Drug Reviews Vol. 12, No. 3-4, pp. 250-275 © 2006 tivity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB 1 agonists are being introduced for pain treatment, it comes out that an indirect cannabinomimetic had been extensively used (and sometimes overused) for more than a century.

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Section: Pharmacological Effectsmentioning

confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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“…dose of only 5 mg/kg paracetamol (administered as propacetamol), by which an initial serum concentration of 14 mg/L was reached, yielded sufficient analgesia [9]. A study by Beck et al demonstrated a C max of only 10.4 mg/L and 17.2 mg/L after rectal administration of paracetamol at 20 mg/kg and 40 mg/kg, respectively [10]. Furthermore, another study compared the bioavailability of paracetamol after oral and i.v.…”

Section: Introductionmentioning

confidence: 99%

Paracetamol for intravenous use in medium- and intensive care patients: pharmacokinetics and tolerance

Maat

Tijssen

Brüggemann

et al. 2010

Eur J Clin Pharmacol

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Purpose We studied the pharmacokinetics of paracetamol and determine the incidence of hypotension after intravenous administration in medium-(MCU) and intensive care (ICU) patients. Methods All patients on the ICU/MCU starting with paracetamol i.v. were included, yielding 38 patients. Blood samples were collected at predetermined time points to determine paracetamol serum concentration. The number of patients with a clinically relevant reduction in systolic blood pressure (SBP) and the number of patients that needed intervention to regain an acceptable blood pressure level were assessed. Results Overall, pharmacokinetic data were roughly comparable with earlier publications, but differences were noted in the subgroup ICU patients. Also, there was a trend to a larger peak serum concentration (p=0.052) and a significantly smaller volume of distribution (p=0.033) in MCU patients compared with ICU patients. Twenty-two percent (22%) and 33% of patients had a clinically relevant reduction in systolic blood pressure (SBP) 15 and 30 min after start of paracetamol infusion, respectively. In six patients (16%), an intervention was needed to correct blood pressure. Overall, SBP was significantly reduced at T=15 min and 30 min postinfusion (p<0.003 at both time points) when compared with SBP at the start of paracetamol infusion. Conclusions Further research on differences in paracetamol pharmacokinetics between ICU and MCU patients is warranted, as these differences might result in differences in efficacy. Furthermore, administration of paracetamol i.v. as potential cause of hypotension in the critically ill patient must not be overlooked.

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“…Beck et al carried out a study among patients undergoing gynecological surgery involving vaginal and abdominal hysterectomies, in which they used paracetamol 20 mg/kg, 40 mg/kg alone and paracetamol 20 mg/kg single rectal dose in combination with diclofenac sodium 100 mg with a observational period of 24 hour after surgery, the result showed that combination of drugs had better pain management than paracetamol alone [8]. Breivik et al carried out study in patients undergoing dental surgery with impacted ΙΙΙrd molar tooth, he used diclofenac 100 mg, paracetamol 1000 mg alone and diclofenac 100 mg with paracetamol 1000 mg single rectal dose with 8 hours of observational period [9].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Diclofenac with Different Preparation of Paracetamol for Post-Operative Analgesia Following Laparoscopic Cholecystectomy

Prakash¹

2016

J Anesth Clin Res

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Pain following surgery remains a very important concern which can lead to detrimental effect over cardiovascular system, central nervous system and respiratory system. To minimise pain several analgesics are used. In that matter multimodal analgesia with diclofenac and paracetamol combination is regularly used. The paracetamol available commercially is in different formulation; Paracetamol 100 mL solution for infusion (P), containing paracetamol, cysteine hydrochloride monohydrate, disodium phosphste dihydrate, hydrocholoric acid, mannitol and sodium hydroxide and Paracetamol and lignocaine 2 mL injection (PL), containing paracetamol, lignocaine hydrochloride and benzyl alcohol. We studied comparing both the formulations of these paracetamol in combination with diclofenac in laparascopic surgeries and we did not find any significant difference between these two in terms of demography, VAS, VRS and any other side effects. However the major difference in the cost between these two formulations makes a significant impact in the economic burden.

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The Pharmacokinetics and Analgesic Efficacy of Larger Dose Rectal Acetaminophen (40 mg/kg) in Adults: A Double-Blinded, Randomized Study

Cited by 39 publications

References 11 publications

Paracetamol: New Vistas of an Old Drug

Paracetamol: New Vistas of an Old Drug

Paracetamol for intravenous use in medium- and intensive care patients: pharmacokinetics and tolerance

A Comparative Study of the Diclofenac with Different Preparation of Paracetamol for Post-Operative Analgesia Following Laparoscopic Cholecystectomy

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