Stability of a factor-analytic description of smoking behavior

Three types of human smoking behavior, identified by factor analysis of questionnaire responses, were found to exhibit a stable structure in a series of different populations and environments. Type I smoking behavior is closely related to a personally perceived need for tobacco products. Types II and III are related to psychosocial-sensorimotor rewards and the intensification of pleasure, respectively. The typology is easily detectable and remarkably constant in the following populations: staff, employees, and patients of a teaching hospital in London, England; urbanites and suburbanites of mixed ages in a part of metropolitan Denver, Colorado, U.S.A.; college students in Fort Collins, Colorado, U.S.A., elderly urbanites and suburbanites in the metropolitan areas of (a) Stockholm, Sweden and (b) Göteborg, Sweden; and the adult children of the Swedish groups (a) and (b).     

Nationwide drug-dispensing data reveal important differences in adherence to drug label recommendations on CYP2D6-dependent drug interactions

AIMS

The study aimed to investigate the clinical adherence to drug label recommendations on important drug–drug interactions (DDIs). Dispensing data on drug combinations involving selective serotonin reuptake inhibitor (SSRI) antidepressants could help to identify areas for intensified medical education.

METHODS

This was a retrospective, cross-sectional analysis of individual dispensing data regarding all individuals ≥15 years old in Sweden. The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole). Odds were calculated between each CYP2D6 drug and the corresponding comparator drug in patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline, respectively. The odds ratio (OR) was calculated by dividing the obtained odds in patients on fluoxetine/paroxetine by the corresponding odds in patients on citalopram/escitalopram/sertraline.

RESULTS

Compared with patients that were dispensed citalopram/escitalopram/sertraline, patients dispensed fluoxetine/paroxetine had lower prescribing rates of metoprolol (adjusted OR 0.80; 95% confidence interval 0.76, 0.85), donepezil (0.65; 0.49, 0.86) and galantamine (0.58; 0.41, 0.81). In contrast, the use of prodrugs codeine (compared woth propoxyphene) or tamoxifen (compared with anastrozole) was similar among patients on fluoxetine/paroxetine and citalopram/escitalopram/sertraline (adjusted OR 1.03; 0.94, 1.12 and 1.29; 0.96, 1.73, respectively).

CONCLUSIONS

Clinically important DDIs that are associated with impaired bioactivation of prodrugs might be more easily neglected in clinical practice compared with DDIs that cause drug accumulation and symptomatic adverse drug reactions.     

Effects of renal insufficiency on the pharmacokinetics and pharmacodynamics of opioid analgesics

The disposition and pharmacologic activities of morphine, meperidine, methadone, propoxyphene, dihydrocodeine, and codeine are reviewed. Dose-related toxicities of these opioid analgesics include mental obtundation, respiratory depression, and hypotension. Furthermore, convulsions have been associated with normeperidine and cardiac toxicities with norpropoxyphene. Hepatic metabolism is the primary route of elimination, except for methadone, for which there is also significant renal excretion. Although the pharmacokinetics of morphine are unchanged in renal insufficiency, accumulation of active metabolites may lead to narcosis. Similar accumulation of normeperidine and norpropoxyphene, metabolites of meperidine and propoxyphene, respectively, as well as propoxyphene itself, and dihydrocodeine and codeine may explain reports of adverse reactions in patients with impaired renal function. A high index of suspicion of opioid-induced toxicities should be maintained in patients who have renal dysfunction and receive opioids.     

Effect of midbrain raphe lesion on the antinociceptive action of morphine and other analgesics in rats

The antinociceptive action of several analgesics was studied by two methods: the hot-plate and the tail compression tests.Lesions of the midbrain raphe, which produce a marked depletion of serotonin in the forebrain, antagonize the analgesic effect of morphine but not that of methadone, meperidine, codeine and propoxyphene.It is concluded that the serotonin involvement suggested for the analgesic action of morphine cannot be generalized to other analgesics.     

Utilisation of antibiotics in young children: opposite relationships to adult educational levels in Danish and Swedish counties

Background Antibiotic utilisation varies profoundly among and within countries, and the extent of antibiotic utilisation correlates with the frequency of bacterial resistance, particularly among children. Hence, it is important to assess which factors may influence prescribing. In addition to variations in morbidity, health-care organisation, drug regulatory and supply systems, prescriber's attitudes, parents' behaviour, attitudes and socio-economic positions seem important. We compared socio-economic position (educational level of adults) and antibiotic utilisation in children in the municipalities within a Danish and a Swedish county which are geographically close, have similar social and economic development, and similar drug regulatory and supply systems.Methods Data on antibiotic utilisation (1998), expressed in defined daily doses per 1000 inhabitants per day (DDD/TID), were obtained from the Copenhagen County Health Insurance register and from the National Corporation of Swedish Pharmacies. Data on municipal educational levels were obtained from Statistics Denmark and Statistics Sweden.Results The utilisation of antibiotics in 0- to 6-year-old children was higher in the Swedish than in the Danish county but varied between the municipalities within both the Swedish (9.6–17.7 DDD/TID) and the Danish (8.0–12.9 DDD/TID) counties. Most notably, utilisation rates correlated negatively with the education levels in the Danish (r=–0.539, P=0.021) but positively in the Swedish (r=+0.390, P=0.025) municipalities.Conclusion The observed variations in antibiotic prescribing may reflect different parental and/or prescriber attitudes towards use of antibiotics and they emphasise that antibiotic prescribing is influenced by factors other than the prevalence of bacterial infections. Relationships between socio-economic position (educational level) and drug utilisation should not be generalised from one area to another.     

Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine

Drugs and alcohol often occur together in fatal poisonings, complicating the process of determining the cause of death. Especially when found in concentrations generally regarded as toxic but not lethal, the question arises whether the combination of sublethal amounts was the likely cause of death. In this study, we examined poisoning deaths involving amitriptyline, propoxyphene and promazine, which are, after benzodiazepines, the most frequently occurring drugs in Finnish alcohol-related poisonings. From the forensic toxicology database, covering the years 1995-2002, we extracted 332 fatal poisonings, calculated median blood alcohol and drug concentrations, constructed concentration-concentration and concentration-response curves and evaluated the significance of the presence of therapeutic amounts of benzodiazepines. Median amitriptyline and propoxyphene concentrations were lower in alcohol-related cases than in clean drug poisonings. Correspondingly, the median blood alcohol concentrations in all drug-related poisonings were 1.5-2.2 mg/g lower than that found in clean alcohol poisonings. Alcohol concentration proved to be a more sensitive indicator of alcohol-drug interaction than drug concentration. This result suggests that when alcohol is present, relatively small overdoses of the studied drugs may result in fatal poisoning. In this context, fatal drug and alcohol concentrations and the issue of determining the most important agent in fatal drug-alcohol intoxications are discussed.     

Correlates of Skin and Soft Tissue Infections in Injection Drug Users in a Syringe-Exchange Program in Malmö, Sweden

Background: Injection drug users (IDUs) are at increased risk of various medical conditions, including bacterial skin and soft tissue infections (SSTIs). SSTIs, which are painful and can lead to life-threatening complications, are common but scarcely studied. Objectives: To investigate life time, past 12 month and past 30-day prevalence for SSTI related to injection drug use, in IDUs at Malmö syringe exchange program (Malmö SEP). To investigate factors associated with having ever had an SSTI. Methods: IDUs were recruited from Malmö SEP (N = 80). They participated in a survey with questions about demographics, drug use, and experience of SSTIs. Factors independently associated with self-reported SSTI ever were assessed using logistic regression analysis. Results: The lifetime reported prevalence of SSTI was 58%, past 12 months 30%, and past 30 days 14%. Factors independently associated with SSTI ever were age (adjusted odds ratio [AOR] = 1.09; 95% confidence interval [CI] = 1.01–1.18), female sex (AOR = 6.75; 95% CI = 1.40–32.47), having ever injected prescribed drugs (AOR = 52.15; 95% CI = 5.17–525.67), and having ever injected in the neck (AOR = 8.08; 95% CI = 1.16–56.08). Conclusions/Importance: SSTI is common among IDUs in Malmö. Women and those injecting in the neck or injecting prescribed drugs (crushed tablets/liquids), are more likely to have had an SSTI.     

Nonformulary drug requests at an academic hospital in Germany – the role of general practitioners' long-term medication

Objective: To determine the influence of general practitioners' outpatient medication on nonformulary drug requests in university hospitals. Methods: During a period of 1 year every nonformulary drug request at the Göttingen University Hospital was analysed (reason for request, drug class). A second analysis examined whether the introduction of a new order form that allowed the prescribing physician to mark a box to declare that this request is due to general practitioner's outpatient therapy influenced the rate of requests. Results: During 12 months a total of 6,281 nonformulary drugs were ordered from the pharmacy, 1,077 (17.1%) of them because of outpatient medication. The percentage of requests according to general practitioners' outpatient medication was about 11% in both the medical and the surgical departments. The rate was rather high in the departments of psychiatry and orthopaedic surgery (39% and 60%, respectively). With the introduction of the new order form, there was a significant increase in the general practice based rate of nonformulary requests on the general surgical wards (from 10.8% to 19.9%). Only a minority of requests (14%) represented drugs of unproven efficacy. Conclusion: Since nonformulary requests attributable to previous outpatient medication accounts for less than 20% and since only a minor portion of them lack scientific proof of efficacy we suggest that hospital doctors and clinical pharmacologists should avoid a drug policy, which is too restrictive, and support maintenance of chronic medication initiated by general practitioners. Especially in the department of psychiatry, nonformulary requests seem to be justified by patient needs.     

Proceedings of the 18th International Symposium on Medicinal Chemistry

The International Symposium on Medicinal Chemistry (ISMC), which is organized in Europe every two years, summarizes the advances and outlines the prospects in this field. In 2004, the 18th ISMC was held in Copenhagen and Malmö, two neighboring cities of Denmark and Sweden, respectively, which are separated by Öresund and connected by a 15-km bridge over this strait.