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PubMed1980

Cytogenetical action of Paracetamol on meiotic cells of male mice.

Cytogenetical effects of the analgesic and antipyretic agent Paracetamol have been studied on meiotic cells of C3 H/He strain male mice for a period of five weeks after administering it at 0.625, 1.25 and 2.5 mg doses. Two series of experiments were carried out. In the single dose series the animals received the drug only once, while in the cumulative series, simulating continuous therapy, the drug was given consecutively to the same animals for three days at 24 h intervals. Adequate controls were employed. Quantitative studies have been made and statistical tests applied to the data. Univalents of auto- and sex-chromosomal types were higher during the first week in both series. There was a preponderance of autosomal univalents in all doses over the sex chromosomal ones up to the fourth week. Polyploid cells and translocations occurred with a low incidence. The implications of these observations are discussed.

Acetaminophen↗
PubMed1995

Nonsteroidal antiinflammatory agents. XXIII. Synthesis and activity of stereomeric (+/-)-erythro- and (+/-)-threo-2-(4-biphenylyl)-3-hydroxy-2-methyl-3-phenyl-propionic acids.

In pursuing our research on the NSAIDs, the diastereomeric (+/-)-erythro- and (+/-)-threo-2-(4-biphenylyl)-3-hydroxy-2-methyl-3-phenyl-propionic acids (4 and 5) were synthesized; the last was also resolved in its optical isomers (6 and 7). The attribution of the relative configuration to 4 and 5 was performed by means of X-ray analysis. The compounds were tested for their antiinflammatory activity. The acid 4, which resulted very interesting, was tested also for analgesic and antipyretic activity, as well as for behavioural effects, gastric tolerability and acute toxicity. On the basis of the obtained data, this compound resulted a very promising one.

Animals↗
PubMed1995

Non-steroidal anti-inflammatory drugs in domestic animals: II Disposition and clinical indications.

Most non-steroidal anti-inflammatory drugs (NSAID's) have similar absorption and disposition characteristics. Absorption after oral administration is good, extensive plasma protein binding results in a small volume of distribution, and excretion of metabolites occurs mainly in the urine after hepatic biotransformation of the active drug. The main clinical indications for use of NSAID's are anti-inflammatory, analgesic and antipyretic, and an increasing list of new indications are continually being found. The disposition, pharmacokinetics and clinical indications of non-steroidal anti-inflammatory drugs in domestic animals are reviewed.

Animals↗
PubMed1995

Trichinosis. Still a public health threat.

Trichinosis remains a worldwide public health problem, although most US physicians have little or no experience with the disease. A history of exposure to raw or undercooked pork and findings of myopathy, eosinophilia, and periorbital edema are characteristic. The diagnosis can be confirmed with tissue biopsy or serodiagnostic testing. Mild infections respond to limited bed rest and use of analgesics and antipyretics. More severe cases can be treated effectively with corticosteroids and anthelminthics.

Adult↗
PubMed1976

Clinical pharmacology of fenoprofen: a review.

This review summarizes available data concerning fenoprofen. The pharmacodynamics, in vivo interactions, gastrointestinal microbleeding, screening for anti-inflammatory action, and tests for antipyretic and analgesic efficacy are discussed.

Animals↗
PubMed1995

Stimulated hepatic tissue repair underlies heteroprotection by thioacetamide against acetaminophen-induced lethality.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that causes massive centrilobular hepatic necrosis at high doses, leading to death. The objectives of this study were to test our working hypothesis that preplaced cell division and hepatic tissue repair by prior thioacetamide (TA) administration provides protection against APAP-induced lethality and to investigate the underlying mechanism. Male Sprague-Dawley rats were treated with a low dose of TA (50 mg/kg, intraperitoneally [i.p.]) before challenge with a 90% lethal dose (1,800 mg/kg, i.p.) of APAP. This protocol resulted in a 100% protection against the lethal effect of APAP. Because TA caused a 23% decrease of hepatic microsomal cytochromes P-450, the possibility that TA protection may be caused by decreased bioactivation of APAP was examined. A 30% decrease in cytochromes P-450 induced by cobalt chloride failed to provide protection against APAP lethality. Time course of serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) indicated that actual infliction of liver injury by APAP peaked between 12 to 24 hours after the administration of APAP, whereas the ultimate outcome of that injury depended on the biological events thereafter. Although liver injury progressed in rats receiving only APAP, it regressed in rats pretreated with TA. Acetaminophen t1/2 was not altered in TA-treated rats, indicating that significant changes in APAP disposition and bioactivation are unlikely. Moreover, hepatic glutathione was decreased to a similar extent regardless of TA pretreatment, suggesting that decreased bioactivation of APAP is unlikely to be the mechanism underlying TA protection. [3H]Thymidine incorporation studies confirmed the expected stimulation of S-phase synthesis, and proliferating cell nuclear antigen studies showed a corresponding stimulation of cell division through accelerated cell cycle progression. Intervention with TA-induced cell division by colchicine antimitosis ended the TA protection in the absence of significant changes in the time course of serum enzyme elevations during the inflictive phase of APAP hepatotoxicity. These studies suggest that hepatocyte division and tissue repair induced by TA facilitate sustained hepatic tissue repair after subsequent APAP-induced liver injury, producing recovery from liver injury and protection against APAP lethality.

Acetaminophen↗
PubMed1993

[A fatal case due to intoxication with seven drugs detected by GC-MS and TDx methods].

A twenty-year-old woman was suspected to ingest large amounts of 4 kinds of over-the-counter analgesic and antipyretic drugs, and was found dead. Drugs and poisons were screened by TOXI-LAB drug detection system in the serum and urine, and analyzed by GC-MS and TDx system in the blood, urine, organ tissues and contents of stomach and small intestine. The concentrations (microgram/g) of bromisovalum, apronalide, ibuprofen, ethenzamide, acetaminophen and caffeine in the heart blood were 36.5, 7.58, 43.1, 16.9, 1.22 and 177, respectively. Salicylic acid concentration in the serum was 82.1 micrograms/ml. The concentrations of bromisovalum and caffeine are high enough to be lethal levels. Neither fatal pathological findings nor traumatic wounds were seen. The overdose of both bromisovalum and caffeine and synergistic, additive or combined effects of other 5 drugs above are considered to be her cause of death.

Acetaminophen↗
PubMed1993

Ibuprofen as an over-the-counter drug: is there a risk for renal injury?

Ibuprofen has recently been introduced as over-the-counter drug in several countries. The question has been raised whether or not the increased availability and use of ibuprofen as over-the-counter drug will be associated with an increased incidence of nephrotoxic side-effects. It is unquestionable that ibuprofen can cause renal damage, including functional acute renal failure, water and electrolyte disorders, and interstitial nephritis. Analgesic nephropathy is not a documented consequence of ibuprofen therapy. Renal side-effects of ibuprofen appear to be dose-dependent, and were not reported at the recommended dosage as over-the-counter drug (0.2-0.8 g/d) except for a single child. Even at anti-inflammatory doses (> 1.6 g/d), renal side-effects are almost exclusively encountered in patients with low intravascular volume and low cardiac output particularly in old age. Alternative analgesic and antipyretic agents display no less risk for renal injury than ibuprofen.

Acute Kidney Injury↗
PubMed1993

Synthesis and some properties of two salsalate derivatives.

The synthesis of esters of 2-hydroxy benzoic acid-2-carboxyphenyl ester (salsalate) with guaiacol for the treatment of inflammatory bronchopneumopathies is reported. The antiinflammatory, analgesic and antipyretic activities of these derivatives were evaluated, together with their antioxidant, mucolytic and broncho-bacteriostatic properties in comparison to acetylsalicylic acid.

Animals↗
PubMed1993

[Self-care measures recorded for acute pathology in primary care].

OBJECTIVE: To quantify and describe the self-treatment existing among users requesting a consultation about an illness which had commenced in the previous 15 days. DESIGN: Observational prospective study. SETTING: Primary care in a semi-rural environment. Family Medicine Unit in Valls (Tarragona). PATIENTS AND OTHERS PARTICIPANTS: The study included all those people who attended the Unit, whose illness had begun during the previous 15 days and who were attending with this illness for the first time. The following variables were recorded: gender, age, symptomatology and whether they had taken self-treatment measures (self-medication and/or non-pharmacological measures). MEASUREMENTS AND MAIN RESULTS: A total of 375 patients were recorded: 59.5% women and 40.5% men. The most common symptoms were pain (50.1%) and temperature (15.2%). 69.9% of the patients (CI 4.75) had treated themselves: there were no significant differences as regards age and gender. An analysis shows that 18.7% used nonpharmacological measures; 75.9% took some drug; and 5.4% used non-pharmacological measures plus a drug. The most used pharmacological groups were analgesics and antipyretics (40.9%, p < 0.001). CONCLUSIONS: Self-treatment is very common in the Primary Care environment. Professionals and health planners will have to bear this very much in mind, in order both to strengthen its positive implications and correct any negative aspects found.

Acute Disease↗
PubMed1995

Studies on the gastric tolerability of the new non-steroidal anti-inflammatory drug amtolmetin guacyl.

Unexpectedly high levels of gastric tolerance to the new non-steroidal anti-inflammatory drug (NSAID) amtolmetin guacyl (CAS 87344-06-7, MED15) were observed in clinical practice. Further investigation of the drug was, therefore, undertaken in order to evaluate its gastrointestinal side-effects in animals. This new agent, which possesses high anti-inflammatory, analgesic and antipyretic activity, was recently introduced into medical therapy. In rats, repeated administration of MED15, even at high dosages, failed to produce any adverse effects on the gastric mucosa, unlike the reference NSAIDs used; the effect on the gastric mucosa was evaluated macro- and microscopically with a staining technique. In immature rat isolated stomachs MED15 strongly down-regulated the HCl output evoked by histamine, acetylcholine and gastrin. An effective NSAID which presents the added advantage of antisecretory properties has not previously been described amongst the many currently available, and reverses the dogma of the inevitable correlation between NSAID assumption and gastrointestinal reactions.

Animals↗
PubMed1975

A review of benorylate - a new antirheumatic drug.

Benorylate (Benoral, Benortan) is the esterification product of paracetamol and acetylsalicylic acid. It has anti-inflammatory, analgesic and antipyretic properties. Benorylate is probably absorbed as the intact molecule which accounts for its good gastric tolerance. After absorption, benorylate is hydrolysed into its components, salicylate and paracetamol, which then follows the usual routes of metabolism. Benorylate per se is also found in inflamed tissue and several studies, both in vivo and in vitro, have shown that it probably has an anti-inflammatory action of its own. Pharmacokinetic studies have shown that a twice daily administration of benorylate should be sufficient for a therapeutic effect and this has been confirmed by its use in patients. Clinical studies have compared benorylate with aspirin, indomethacin, ibuprofen and phenylbutazone and have shown its value in rheumatoid arthritis, osteoarthrosis and other musculoskeletal conditions. The overall tolerance is excellent. Some minor gastric disturbances are reported from time to time, but these are less than with comparable doses of aspirin. Studies measuring occult blood loss in the stools have shown that this is not a significant problem with benorylate and that the majority of patients lose no more blood than the controls.

Anti-Inflammatory Agents↗
PubMed1996

Tolerability of nabumetone: a pilot in vitro study showing absence of injury to articular cartilage.

Nabumetone, a compound of the naphthylalkanone class, has shown considerable anti-inflammatory, analgesic and antipyretic effects, together with high systemic and organ-specific tolerability. Its reputation for tolerability has been increased by an in-vitro study evaluating the mature collagen metabolism's markers under nabumetone treatment, which shows that, nabumetone does not interfere with collagen synthesis. Therefore, unlike some nonsteroidal anti-inflammatory drugs, nabumetone might not be injurious to articular cartilage. This feature makes nabumetone even safer for long-term treatment of rheumatic and orthopaedic conditions.

Adult↗
PubMed1997

Self medication--a growing concern.

31% persons practiced self medication. They were more in 31-40 years (26.9%) and 41-50 years (30.8%). Males were more than females in self prescribers. Illiterate (23.1%) and graduates (26%) were more common self medicators, while labourers (26%) and business men (19.3%) were more involved in self medication. Fever (17.4%), cough (22.2%), boils (7.6%) and acidity (6.8%) were the common complaints for self-prescription. Thus analgesics and antipyretics, (30.9%), tonics (16.1) and antibiotics (10.7%) were commonly used drugs by the customers. Most of the information of drugs was from friends or neighbours (30.8%) or chemist (23.1%).

Adolescent↗
PubMed1996

[A case-control study of childhood leukemia].

A 1:1 matched case-control study was conducted to investigate the etiological factors of childhood leukemia. It was found that there were five risk factors: (1) children living in the environmental pollution area, OR (95% CI) = 2.84 (1.14-7.10); (2) exposure to extreme low frequency electronmagnetic field (ELF), OR (95% CI) = 2.01 (1.18-3.42); (3) history of postnatal X-ray exposure, OR (95% CI) = 4.53 (1.68-12.21); (4) history of taking chloramphenicol, OR (95% CI) = 3.60 (1.62-8.01); (5) history of taking, antipyretic or analgesic drugs, OR (95% CI) = 1.93 (1.09-3.42). A protective factor was also discovered. Mothers often eating fish, pork and other meat foods, OR (95% CI) = 0.33 (0.18-0.59). The analysis of the population attributable risk showed that 91% of the childhood leukemia cases might attribute to these five risk factors. The interaction among these etiological factors was estimated. Results showed that there was a positive interaction between the X-ray exposure and chloramphenicol on additive model, the relative excess risk due to interaction (RERI) of childhood leukemia was 3.04.

Adolescent↗
PubMed1998

Management of Fournier's gangrene at the Kenyatta National Hospital, Nairobi.

A prospective study involving the management of forty six patients with Fournier's gangrene was carried out at the Kenyatta National Hospital, Nairobi over a period of two years. The age range was nine to 81 years with a mean of 40.27 years indicating that the lesion is common and affects all age groups in this locality. The majority of patients (60.86%) presented with advanced lesions involving scrotal ulcers (45.65%) and gangrene (15.22%). Results of bacterial culture from scrotal wound swabs isolated multiple organisms in 8.15% of the patients, a point which should be taken into consideration during antibiotic selection. Forty one patients (89.13%) had surgical procedures in addition to antibiotics and other supportive measures. Five other patients (10.87%) who presented with early lesions had medical treatment only with antibiotics, antipyretics and analgesics. The average duration of hospitalisation was sixteen days. Two patients (4.35%) one of whom was HIV positive died from septicaemia during the study period. Recurrent scrotal infection occurred in two patients (4.35%) after discharge from the hospital and were treated satisfactorily at the surgical outpatient clinic.

Adolescent↗
PubMed2003

Safety of oral use of nimesulide in children: systematic review of randomized controlled trials.

BACKGROUND: Nimesulide has been widely used to treat fever in children. Due to reports of adverse drug reactions, discontinuation or modification of its use has been suggested. OBJECTIVE: To evaluate the safety of oral use of nimesulide in children. DESIGN: Systematic review of published randomized controlled trials. SEARCH STRATEGY: Electronic searches of databases (PubMed, Cochrane, Toxnet) for relevant trials upto January 2003 using specified key words. The studies were also identified by searching the references of available meta-analyses and review articles, and bibliography of pertinent references. INCLUSION CRITERIA: Randomized controlled trials in children (less than or equal to 18 years of age) comparing the use of oral nimesulide with placebo or other antipyretic, anti-inflammatory or analgesic agents. OUTCOME: The primary outcome variable included the commonly encountered adverse effects of nimesulide therapy, i.e., hypothermia, abdominal symptoms, gastrointestinal bleeding, and elevated liver enzymes. DATA COLLECTION AND ANALYSIS: One of the authors developed a questionnaire and independently extracted data on methods, type of participants, interventions and outcomes. The meta-analysis was conducted using pooled relative risk with 95% confidence intervals, with random effects model assumption. RESULTS: We identified 16 trials that fulfilled the inclusion criteria. These included 1254 subjects, with mean age between 22 -140 months. Nimesulide was primarily used for its antipyretic (10 trials) or anti-inflammatory and analgesic activity (4 trials). One study each evaluated the symptomatic improvement in ARI and bronchial asthma. The control group included administration of placebo (3 studies), paracetamol (9 studies), and ketoprofen, naproxen, mefanemic acid and aspirin in one study each. The pooled effect sizes of various adverse events as compared between nimesulide and different control groups were: hypothermia (RR: 1.055; 95% CI: 0.184 - 6.047; P = 0.952), abdominal symptoms (RR: 0.464; 95% CI: 0.264 - 0.816; P = 0.008), gastrointestinal bleeding (RR: 0.914; 95% CI: 0.236 - 3.543; P = 0.896), and asymptomatic liver enzyme elevation (RR: 2.678; 95% CI, 0.558-12.853; P = 0.218). Cutaneous and renal adverse effects were not seen in any of the included studies. CONCLUSION: Oral nimesulide is as safe or unsafe as other analgesics-antipyretics for short-term use (less than or equal to 10 d) in children. The drug is best avoided in known or suspected liver disease; caution is warranted while prescribing nimesulide concomitantly with other hepatotoxic drugs. There is limited data for drawing concrete inferences below the age of six months.

Administration, Oral↗