Consumption of non-steroidal anti-inflammatory drugs in Serbia: a comparison with Croatia and Denmark during 2005–2008

Purpose  

To analyze the amount and pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in Serbia and to compare these parameters with those in Croatia and Denmark. The prescribing pattern of NSAIDs in Serbia as a direct indicator of physicians’ knowledge of these agents was also assessed.     

Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a new generation of antithrombotics?

Long-term use of aspirin as an antithrombotic agent is limited by its toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. Addition of a nitric oxide (NO)-releasing moiety to non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to greatly reduce their ulcerogenic properties as well as their renal toxicity. We proposed that similar derivatisation of aspirin may yield a potent, gastrointestinal-sparing antithrombotic drug. Two prototype compounds (NCX-4215 and NCX-4016; Nicox SA) have been evaluated thus far. Each shows comparable or better anti-aggregatory activity to aspirin while not inducing detectable gastric damage. Current studies are aimed at determining what the optimal balance is between nitric oxide release and inhibition of thromboxane synthesis to achieve good antithrombotic activity with low toxicity. NO-aspirin derivatives appear to offer great potential as gastrointestinal-sparing antithrombotic drugs.     

Treatment with non-steroidal anti-inflammatory drugs in patients after myocardial infarction – a systematic review

Introduction: Studies over the past decade have shown that NSAIDs are associated with increased cardiovascular risk and may predispose to myocardial infarction in healthy individuals. Despite this knowledge patients with established cardiovascular disease are frequently treated with NSAIDs. The benefits versus potential harm of treatment need careful assessment.

Areas covered: Observational studies and clinical trials providing information about outcome of NSAID treatment in post MI patients were retrieved; fourteen articles in total: two case-control studies, two randomized double-blind trials and ten cohort studies. The studies had a follow-up time between 30 days and 15 years. Two studies reported of risk of atrial fibrillation, and only one addressed antithrombotic treatment.

Expert opinion: The risk of death and reinfarction in this group of patients is well established. Further studies are needed to investigate factors increasing the risk of atrial fibrillation. The correlation between recommended pharmaceutical treatment post MI and NSAIDs needs to be further examined. None of the studies examined correlated their results to dosages available over the counter.     

Detecting drug–drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs

OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. METHODS: Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. RESULTS: The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. CONCLUSION: The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.     

Association between use of short-acting benzodiazepines and migraine occurrence: a nationwide population-based case–control study

Aim: To evaluate the association between using benzodiazepines (BZDs) with short- or long-acting durations and migraine occurrence.

Methods: The migraine group comprised 9616 subjects older than 20 years and newly diagnosed with migraine between 2005 and 2011, and the comparison group comprised 38,464 subjects without migraine. The BZDs used in the subjects were dichotomously defined as short-acting (half-life ≤24?h) and long-acting substances. A logistic regression model was used to calculate the odds ratio (OR) of migraine associated with BZD exposure and other diseases.

Results: The adjusted OR of migraine associated with BZD exposure was 1.73 (95% confidence interval [CI]?=?1.63–1.84). Either exposure to a short-acting BZD alone or using it combining with a long-acting BZD had significant higher risks of migraine (adjusted OR?=?1.69, 95% CI?=?1.59–1.80; adjusted OR?=?2.06, 95% CI?=?1.91–2.24, respectively), whereas only long-acting BZD use was not associated with an increase of migraine. Meanwhile, sleep disorders, anxiety, and stroke were strongly associated with migraine (adjusted OR?=?2.00, 1.91, and 1.57, respectively).

Conclusions: We observed a significant increase of migraine occurrence in subjects using short-acting BZDs, either alone or in combination with long-acting ones.     

Hospital pharmacists’ roles and attitudes in providing information on the safety of non-steroidal anti-inflammatory drugs in Thailand

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for patients to manage pain and inflammation, especially in older adults. Failure to cope with some adverse drug reactions (ADRs) of NSAIDs could lead to more serious symptoms, therefore, providing useful information about medicine is an important step in protecting patients from developing serious ADRs. The pharmacy service should be a frequent source of medicine information for patients, however in Thailand, little is known about pharmacists’ provision of safety information to patients for management and prevention of these ADRs. Objective Aims of this study were to determine Thai hospital pharmacists’ roles in providing drug safety information and to assess their attitudes towards the importance of giving drug safety education to patients. Setting All government hospitals in north-eastern Thailand. Methods This study was a cross-sectional survey. A total of 761 pharmacists in 287 hospitals in north-eastern Thailand were selected by stratified random sampling. Self-administered questionnaires were sent by post, with two reminders. Main outcome measures Proportion of hospital pharmacists providing ADR information on NSAIDs to patients, factors affecting this provision, and pharmacist attitudes towards drug safety education for patients. Results The response rate was 54.8 % (N = 417), the majority of respondents worked in community hospitals (57.2 %). A total of 347 pharmacists (83.6 %) had informed patients about ADRs, although less than half had informed patients about ADR monitoring and management (36.6 % and 44.1 % respectively). The proportion of time spent in direct patient contact, type of hospital, and other routine work were associated with the frequency of drug safety information provision. Pharmacists had moderately good attitudinal scores towards drug safety education (62.2 ± 5.4), with significantly higher scores found in those who provided most ADR information to patients (60.3 ± 5.2 vs. 62.6 ± 5.4, P = 0.002). The majority (82.2 %) agreed that patient information leaflets should be provided. Conclusions Thai hospital pharmacists’ provision of ADR information for NSAIDs may occur less frequently than is desirable. However, their positive attitude towards provision of ADR information suggests that drug safety education by pharmacists should be routinely provided to patients, particularly patients at high risk of NSAID use.     

Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case–control study

Aims

Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA.

Methods

We used nationwide insurance data to perform a case–control study including 3174 CCA patients diagnosed in 2002–2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose.

Results

Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose–response association was seen when using lovastatin.

Conclusions

Statin use is associated with reduced risk of CCA and there is a dose–response relationship between the use of statins and risk of CCA.     

Role of ATP-sensitive K⁺ channels in the antinociception induced by non-steroidal anti-inflammatory drugs in streptozotocin-diabetic and non-diabetic rats

There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K⁺ channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P < 0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P > 0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K⁺ channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.     

Estimates of the national trend of drugs use during 2000–2030 in China: A population-based mathematical model

BackgroundThe use of synthetic drugs has exceeded heroin to become a major public health concern in China. We aimed to estimate the trend of heroin-only, synthetic drug-only and poly-drug (heroin and synthetic drug) use during 2000–2030 period in China using existing data.MethodsWe used data from the Annual Report on Drug Control in China and peer-reviewed publications. We constructed a mathematical model to estimate the drug use trend based on Monte Carlo simulations.ResultsThe best calibrated model estimated that the number of drug users would increase from 0.86 million to 3,120,059 (95% CI 2,669,214-3,570,904) during 2000–2030 period. The proportion of heroin-only users among the total drug users will decrease from 96.8% (95% CI, 96.6–97.1%) in 2000 to 36.9% (30.1–40.8%) in 2030, while the proportion of synthetic drug-only users will increase from 1.1% (0.9–1.3%) in 2000 to 57.7% (51.7–65.6%) in 2030. In contrast, the proportion of poly-drug users shared an increasing trend during 2000–2016 (from 2.1% (1.5–2.8%) to 15.1 (13.8–17.1%)) but declined to 5.5% (3.4–7.2%) in 2030. Estimated 46,370 (41,634-51,106) heroin-only users and 3767 (3481–4053) synthetic drug only users initiated poly-drug use in 2000. We observed a cross-over in 2012 where more synthetic drug-only users were initiating heroin use than heroin-only users initiating synthetic drug use. There will be estimated 2,094,052 (1,819,830–2,368,274) synthetic drug-only users and poly-drug users 211,407 (177,150–245,664) in 2030.ConclusionsSynthetic drug use will become dominant in drug users in China, but poly-drug use of both heroin and synthetic drugs will remain substantial.     

Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case–control study in a large population-based German database

Purpose  

Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon.