PubMed · 73681
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
K Wiener, J Hooper. 1976-03-27. Plasma-paracetamol estimation.. https://doi.org/10.1016/s0140-6736(76)92831-2
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
CONTEXT: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or specific inhibitors of cyclooxygenase 2 (COX-2). OBJECTIVE: To assess the relative therapeutic efficacy of rofecoxib, celecoxib, and acetaminophen in adults with OA. DESIGN AND SETTING: Randomized, parallel-group, double-blind trial, conducted from June 1999 to February 2000, in 29 clinical centers in the United States. PATIENTS: Three hundred eighty-two patients aged at least 40 years who had OA of the knee that was previously treated with NSAIDs or acetaminophen. INTERVENTIONS: Patients were randomly assigned to receive rofecoxib, 12.5 mg/d (n = 96); rofecoxib, 25 mg/d (n = 95); celecoxib, 200 mg/d (n = 97); or acetaminophen, 4000 mg/d (n = 94) for 6 weeks. MAIN OUTCOME MEASURES: Assessments over days 1 to 6 and over 6 weeks included pain on walking, night pain, pain at rest, and morning stiffness as measured on a Western Ontario McMaster Universities Osteoarthritis Index (100-mm visual analog scale [VAS]) and global response to therapy compared among 4 treatment groups. RESULTS: 79% of patients completed the study. More patients treated with acetaminophen discontinued early due to lack of efficacy than patients treated with COX-2 inhibitors (31% vs 18%-19%). Efficacy assessed in the first 6 days of therapy showed greatest response to rofecoxib, 25 mg/d, followed by rofecoxib, 12.5 mg/d, celecoxib, and acetaminophen, respectively, in terms of relief of pain on walking (-32.2, - 29.0, - 26.4, and -20.6 mm change on the VAS; P</=.04 for all others vs acetaminophen; P =.05 for 25-mg rofecoxib vs celecoxib), rest pain (-21.8, - 18.6, - 15.5, and - 12.5 mm; P</=.02 for either dose of rofecoxib vs acetaminophen and P =.02 for rofecoxib, 25 mg/d, vs celecoxib), night pain (-25.2, - 22.0, - 18.7, and - 18.8 mm; P =.04 for rofecoxib, 25 mg/d, vs both acetaminophen and celecoxib), and morning stiffness (-30.4, - 28.4, - 25.7, and - 20.9 mm; P</=.02 for either dose of rofecoxib vs acetaminophen). Over 6 weeks, rofecoxib, 25 mg/d, provided greatest response for night pain (P<.002 vs celecoxib and P =.006 vs acetaminophen and P =.02 vs rofecoxib, 12.5 mg/d), composite pain subscale (P</=.03 vs all other treatments), stiffness subscale (P</=.04 vs celecoxib and acetaminophen), and physical function subscale (P =.001 vs acetaminophen). Global responses over 6 weeks showed a similar pattern (good or excellent response at week 6: 60%, 56%, 46%, and 39%, respectively; P</=.03 for rofecoxib, 25 mg/d, vs celecoxib and acetaminophen; P =.02 for rofecoxib, 12.5 mg/d, vs acetaminophen). All treatments were generally safe and well tolerated. CONCLUSION: Rofecoxib, 25 mg/d, provided efficacy advantages over acetaminophen, 4000 mg/d, celecoxib, 200 mg/d, and rofecoxib, 12.5 mg, for symptomatic knee OA.
BACKGROUND: The term drug screen is a misnomer since it implies screening for all drugs, which is not possible. Current practice is to limit the testing to the examination of serum for several drugs such as ethanol, acetaminophen, salicylate, and of urine for several specific drugs or classes of drugs. In the emergency setting the screen should be performed in less than one hour. Controversies continue to exist regarding the value of urine drug testing in the medical setting. The reasons for these include the drugs involved, the sample, the methods utilized to perform the tests, and the level of understanding of the physician using the data, all of which are closely related to the other. METHODS: Current automated methods provide rapid results demanded in emergency situations, but are often designed for, or adapted from, workplace testing and are not necessarily optimized for clinical applications. Furthermore, the use of these methods without consideration of the frequency in which the drugs are found in a given area is not cost-effective. The laboratory must understand the limitations of the assays used and provide this information to the physician. Additionally, the laboratory and the physicians using the data must cooperate to determine which drugs are appropriate and necessary to measure for their institution and clinical setting. In doing so it should be remembered that for many drugs, the sample, urine, contains the end product(s) of drug metabolism, not the parent drug. Furthermore, it is necessary to understand the pharmacokinetic parameters of the drug of interest when interpreting data. Finally, while testing for some drugs may not appear cost-effective, the prevention or reduction of morbidity and mortality may offset any laboratory costs. CONCLUSIONS: While the literature is replete with studies concerning new methods and a few regarding physician understanding, there are none that we could find that thoroughly, objectively, and fully addressed the issues of utility and cost-effectiveness.
Camel lens zeta-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor (K(i) 0.64 mM) with respect to NADPH and non-competitive inhibitor (K(i) 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5' phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect zeta-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of zeta-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH.