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Biomedical subjects

Lars Slørdal

Publications and source records attributed to Lars Slørdal.

17 recordsLinked to original sources

[COX-2 inhibitors--one step forward and two steps back].

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors are widely used. They have no advantages in terms of efficacy, and it is not documented that they cause fewer adverse effects than conventional NSAIDs. MATERIAL AND METHODS: The adverse effects of rofecoxib, celecoxib and other NSAIDs are reviewed. Relevant literature was identified on Medline and in the reference lists in key articles. RESULTS: Rofecoxib and the novel COX-2 inhibitors etoricoxib and valdecoxib have a higher degree of COX-2 selectivity than traditional NSAIDs. Celecoxib is less COX-2 selective and appears to be similar to diclofenac. Rofecoxib induces thromboembolic adverse effects more frequently than conventional NSAIDs. INTERPRETATION: The cardiovascular problems conferred by rofecoxib are probably a class effect and thus inducible by other selective COX-2 inhibitors. Pending comprehensive safety data, caution is warranted regarding the use of these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials.

OBJECTIVE: To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee. DESIGN: Systematic review and meta-analysis of randomised placebo controlled trials. STUDIES REVIEWED: 23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years. MAIN OUTCOME MEASURE: Change in overall intensity of pain. RESULTS: Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31). CONCLUSION: NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended.

Anti-Inflammatory Agents, Non-Steroidal↗

[Problem forte--is paracetamol-codeine combination rational?].

BACKGROUND: Combination drugs containing codeine and paracetamol are widely prescribed in Norway. MATERIAL AND METHODS: We reviewed relevant literature identified through searches on Medline or found in the reference lists of important articles. RESULTS: Codeine mediates its analgesic effect through the active metabolite morphine, a reaction which is catalysed by the cytochrome P450-isoenzyme CYP2D6. Approximately 7-10 % of the population does not express functional CYP2D6; for them codeine have no analgesic effect. They may, however, experience side effects from codeine. Used alone, codeine is an inefficient analgesic. Meta-analyses have shown little therapeutic advantage by adding codeine to paracetamol. INTERPRETATION: Codeine is an opiate with uncertain and unpredictable effects. The therapeutic benefit from the codeine component in combination with paracetamol is small, even in single dose evaluations. In chronic use, the therapeutic efficacy is most likely outweighed by side effects, including development of tolerance and abuse.

Acetaminophen↗

[Heroin: a useful analgesic?].

BACKGROUND: In some countries, heroin is widely used as an analgesic agent. MATERIAL AND METHODS: The literature describing the history, pharmacology and analgesic use of heroin was reviewed. RESULTS: Heroin is a semi-synthetic morphine derivative. A century ago it was considered a panacea with numerous indications. Today it is best known as a drug of abuse, but is still in use as an analgesic. Most studies that compare heroin with other analgesics have methodological shortcomings; however, they generally indicate that heroin has a clinical effect not very different from morphine. An better aqueous solubility as compared to morphine may in some situations be advantageous. Because of a proposed incomplete cross-tolerance between heroin and other opioid analgesics, it may be used if the patient shows sub-therapeutic response to first-line opioids. INTERPRETATION: Although not well documented, heroin appears to be an effective analgesic with certain properties different from those of morphine. It may be of clinical value in conditions with acute and/or terminal pain.

Adult↗

[What information is given on adverse drug reactions from new drugs?].

BACKGROUND: It is not known to what extent information on previously unknown adverse reactions is communicated to doctors after the approval of a new drug. MATERIAL AND METHODS: We included seven drugs, approved between 1982 and 1995 and the first in their class to be approved in Norway. We recorded the number of adverse reactions listed in the annual editions of the Norwegian physicians' desk reference(Felleskatalogen) from the first edition that included the drug and up until the 2001 edition. RESULTS: Only 51 % of the adverse reactions listed in the 2001 edition were included in the first post-approval edition. On average, 1.6 new adverse reactions were added for each drug every year. By contrast: in a group of 12 drugs approved before 1970, 0.14 new adverse reactions were added for each drug every year between 1989 and 2001. INTERPRETATION: With a new drug it is to be expected that many adverse reactions are not acknowledged as such. Caution is warranted because of the fact that even though it is not listed in the physicians' desk reference, any event appearing in a patient exposed to a new drug may be an adverse reaction.

Adverse Drug Reaction Reporting Systems↗