Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study.

BACKGROUND: About 500 drug poisoning deaths involving paracetamol (acetaminophen) occur every year in England and Wales. To reduce the number of deaths, regulations were introduced in 1998 to restrict the sale of paracetamol. In this paper, we evaluate the impact of these regulations. METHODS: Mortality data for England and Wales were provided by the Office for National Statistics. Deaths were defined as due to compound paracetamol (paracetamol in combination with another analgesic, a low dose opioid or other ingredients) or paracetamol only, with or without alcohol or other drugs. The Department of Health provided data on all hospital admissions with a primary diagnosis of paracetamol poisoning. RESULTS: Mortality rates for paracetamol only were similar for males and females, and decreased from about 4.5 to 2.8 per million between 1997 and 1999 and again from about 3.1 to 2.2 per million between 2001 and 2002. These falls may be attributable to random variation in the rates. Deaths involving compound paracetamol, which were not subject to the 1998 regulations, remained relatively constant over the study period. There was evidence of a decreasing trend in paracetamol only mortality rates and this followed overall trends for other drug poisoning excluding opioids and drugs of misuse. Hospital admissions due to paracetamol poisoning increased from about 27 000 to 33 000 between 1995/1996 and 1997/1998 and then decreased to 25 000 in 2001/2002. There were almost 50 per cent more admissions for females than males, with the highest admission rates amongst females aged 15-24 years old. CONCLUSIONS: Between 1993 and 2002, mortality rates and hospital admissions due to paracetamol poisoning declined. However, the contribution of the 1998 regulations to this decline is not clear. Paracetamol poisoning continues to be an important public health issue in England and Wales and represents significant workload for the NHS in England

A look inside the association codeine-paracetamol: clinical pharmacology supports analgesic efficacy

Acute and chronic pain often requires a multimodal approach. Combination therapy reduces the number of individual daily administrations and improves patient's compliance with the prescribed analgesic treatment. Despite the association codeine/paracetamol is one of the most widely used central analgesic, the exact mechanism of action, particularly of paracetamol, is still object of pharmacological research. Recent findings showed that paracetamol may act through cerebral cyclo-oxygenase, descending opioidergic inhibitory pathways, serotonin pathway, and the endocannabinoid system; while codeine activity seems to related not only to its conversion to morphine, as previously known, but also by itself and through its metabolites, such as norcodeine (NORC) and codeine-6-glucuronide (C-6-G). The addition of codeine to paracetamol significantly improves the analgesic action and reduces the number needed to treat (NNT) from 5 to 2.3-3.1. Recent warnings about the risk of its metabolism related to CYP450 and its genetic variability in general population should be mainly considered when the association is used in paediatric patients undergoing tonsillectomy and/or adenoidectomy procedures for obstructive sleep apnoea syndrome (OSAS). In adults, the association codeine/paracetamol has been shown to be effective and safe in different settings: acute pain, trauma patients, and chronic nociceptive pain

Photolysis of in-situ electrogenerated hydrogen peroxide for the degradation of emerging pollutants

This study investigates the degradation of paracetamol, an emerging contaminant widely used as pain and fever reliever, by means of hydrogen peroxide either alone or in combination with UV-C photolysis. In particular, we provide a comparison between the performance of both commercial and electrogenerated H2O2 whose production has been achieved by galvanostatic electrolysis in undivided reactor with a gas diffusion cathode. The performance of the treatments has been assessed in terms of both pollutant decay and mineralization. The influence of the H2O2 to paracetamol molar ratio is discussed. The results show that the electrogenerated hydrogen peroxide, when activated by UV-C irradiation, results in faster degradation and mineralization of paracetamol. However, under the conditions adopted, complete depletion of the total organic carbon (TOC) has never been attained

Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia

The concentrations of 12 pharmaceutical compounds (atenolol, erythromycin, cyclophosphamide, paracetamol, bezafibrate, carbamazepine, ciprofloxacin, caffeine, clarithromycin, lidocaine, sulfamethoxazole and Nacetylsulfamethoxazol (NACS)) were investigated in the influents and effluents of two hospital wastewater treatment plants (HWWTPs) in Saudi Arabia. The majority of the target analytes were detected in the influent samples apart from bezafibrate, cyclophosphamide, and erythromycin. Caffeine and paracetamol were detected in the influent at particularly high concentrations up to 75 and 12 ug/L, respectively. High removal efficiencies of the pharmaceutical compounds were observed in both HWWTPs, with greater than 90 % removal on average. Paracetamol, sulfamethoxazole, NACS, ciprofloxacin, and caffeine were eliminated by between >95 and >99 % on average. Atenolol, carbamazepine, and clarithromycin were eliminated by >86 % on average. Of particular interest were the high removal efficiencies of carbamazepine and antibiotics that were achieved by the HWWTPs; these compounds have been reported to be relatively recalcitrant to biological treatment and are generally only partially removed. Elevated temperatures and high levels of sunlight were considered to be the main factors that enhanced the removal of these compounds

Restricting paracetamol in the United Kingdom to reduce poisoning: a systematic review

Background Paracetamol poisoning is implicated in about 150-200 poisoning deaths per year in England and Wales. We review previous studies assessing the effectiveness of regulations introduced in 1998 to restrict sales of paracetamol and reduce paracetamol poisoning. Methods We searched the following electronic databases: MEDLINE, EMBASE, CINHAL, HIMIC, COCH, APC, CENTRAL and DARE. English language publications between 1998 and 2003 were included. Studies were included if they took place in the United Kingdom and assessed changes in any aspect of paracetamol poisoning following the introduction of the 1998 regulations. Results Twelve studies were identified, which examined several different outcomes. Three studies examined admissions to liver transplant units; all reported reductions. Eight studies evaluated severity of paracetamol poisoning; three reported reductions but five did not. Five out of six studies reported reductions in hospital admissions. One study reported reduced mortality in England and Wales after 1 year while another found no difference in Scotland 2 years after the regulations were introduced. Two studies observed a significant reduction in over-the-counter sales. Studies suffered from several limitations including short follow-up periods, no case definition for paracetamol poisoning and lack of comparison groups. Conclusions The limitations of these studies makes it difficult to draw firm conclusions. They do, however, suggest that the 1998 regulations may have been associated with reduced admissions to liver units and liver transplants, reduced hospital attendance due to paracetamol poisoning and reduced sales of paracetamol. Further research is needed to fully evaluate the impact of the 1998 regulations. In the future, formal evaluation of the impact of similar interventions should be an integral part of policy formation

Sonolysis of levodopa and paracetamol in aqueous solutions.

Pharmaceutical products are often present in wastewater treatment effluents, rivers, lakes and, more rarely, in groundwater. The advanced oxidation methods, like ultrasound, find a promising future in the area of wastewater treatment. The aim of this paper is to evaluate the influence of several parameters of the ultrasound process on the degradation of paracetamol, a widely used non-steroidal anti-inflammatory recalcitrant drug found in water and levodopa, the most frequently prescribed drug for the treatment of Parkinson disease. Experiments were carried out at 574, 860 and 1134 kHz of ultrasonic frequency with horn-type sonicator and actual power values of 9, 17, 22 and 32 W at 20 °C. Initial concentrations of 25, 50, 100 and 150 mg L−1 of both products were used. Treatment efficiency was assessed following changes in pharmaceuticals concentration and chemical oxygen demand. The sonochemical degradation of both products follows a pseudo-first-order reaction kinetics. Complete removal of pharmaceuticals was achieved in some cases but some dissolved organic carbon remains in solution showing that long lived intermediates were recalcitrant to ultrasound irradiation. Pollutants conversion and COD removal were found to decrease with increasing the initial solute concentration and decreasing power. The best results were obtained with 574 kHz frequency. Investigations using 1-butanol as radical scavenger and H2O2 as promoter revealed that pollutants degradation proceeds principally through radical reactions, although some differences were observed between both molecules. Addition of H2O2 had a positive effect on degradation rate, but the optimum concentration of hydrogen peroxide depends on the pollutant

Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice

Effect of Durian Fruit Juice (Durio Zibethinus Murr.) to Pharmacokinetic Profile of Paracetamol on Wistar Male Rats (Rattus Norvegicus L.)

Paracetamol is widely used as analgesic and antipyretic agent in treatment of pain and fever. Paracetamol has interaction with carbohydrates and alcohol. Durian is the fruit native of Indonesia, that contain carbohydrates and alcohol. The aims of this research were to study the influence of durian fruit juice to the absorption and elimination kinetics of paracetamol and to know the dose of durian fruit juice that influence the absorption and elimination kinetics of paracetamol. The study was conducted using 16 rats, divided into 4 groups (n=4 per group). Each group was treated the following treatment : control paracetamol (paracetamol 9 mg/200 gBW), dose 1 group (paracetamol 9 mg/200 gBW and 0.675 g/200 gBW of durian fruit juice), dose 2 group (paracetamol 9 mg/200 gBW and 1.350 g/200 gBW of durian fruit juice) and dose 3 group (paracetamol 9 mg/200 gBW and 2.700 g/200 gBW of durian fruit juice). Blood sampling is done from the vein of rat's tail at minutes 10, 20, 30, 40, 60, 90, 120, 180, 240, 300 and 360. The quantitation of paracetamol in plasma was determined by UV spectrophotometer at 243 nm. Result showed that durian fruit juice changed the absorption kinetics of paracetamol, durian fruit juice decreased Ka, Cpmaks and increased Tmaks parameter of paracetamol. Durian fruit juice also changed the elimination kinetics of paracetamol, its decreased Vd, Ke, Cl and increased the value of AUC and T1/2 paracetamol. All doses of durian fruit juice can influence the absorption and elimination kinetics of paracetamol includes Ka, Cpmaks, Tmaks, Vd, Cl, Ke, T1/2 and AUC parameters on wistar male rats (Rattus norvegicus L.)