A nationwide evaluation of off-label drug utilization in Turkey

Background/aim: Off-label drug use (OLDU) is under the control of the Turkish Medicines and Medical Devices Agency (TMMDA) in Turkey. It was aimed to investigate demographic and medical features of patients with OLDU applications in Turkey. Materials and methods: A total of 4426 electronic OLDU application records of the TMMDA were evaluated retrospectively. Information regarding patients? demographic characteristics, diagnoses, requested drugs, institutions, and specialties of the physicians were evaluated. Results: OLDU applications were mostly made by rheumatologists (21.5%) and 95.2% of them were approved by the TMMDA. The mean age of the patients was 35 years and 54.4% of them were female. Off-label drugs were mostly prescribed for patients aged 18?64 years (62.1%) and were most frequently prescribed by physicians from university medical centers (81.0%). Systemic lupus erythematosus (10.1%) was the most common diagnosis. Mycophenolate (16.1%) and rituximab (10.1%) were the most frequently prescribed off-label drugs. There were differences regarding some characteristics of patients and their physicians among most frequently prescribed off-label drugs (P < 0.05). Conclusion: It is noteworthy that OLDU applications showed demographical and institutional differences. It is expected that this study will provide important contributions to physicians working in the relevant area with respect to treatment alternatives of diseases with treatment challenges.

Drug utilization pattern and rational drug use at orthopedics and traumatology outpatient clinics: A cross-sectional study.

OBJECTIVES: The aim of the present study was to assess the prescriptions of patients who were admitted to the orthopedics and traumatology outpatient clinic of a tertiary care hospital according to the WHO prescribing indicators. PATIENTS AND METHODS: Between January 2020 and March 2020, a total of 1,024 patients (273 males, 751 females; mean age: 51.9±13.9 years; range, 19 to 103 years) were included in the study. Only patients who were prescribed drugs and 18 years of age or older were included in the study. The WHO core prescribing indicators were utilized for the assessment of rational drug use. The WHO prescribing indicators percentages between the age categories were analyzed. The average number of drugs between the age categories was also examined. RESULTS: The average number of drugs per encounter was 2.9. The percentage of encounters with an antibiotic prescribed was 2.6% and with an injection prescribed was 10.7%. The percentage of drugs prescribed from essential drugs list was 33.8%. There were no prescriptions consisting generic name of drugs (0%). Polypharmacy was significantly higher in the ≥65 age group compared to the 18-44 age group (p=0.001). CONCLUSION: The percentage of encounters with an antibiotic and injection prescribed were optimal according to WHO standards, while the average number of drugs per encounter was higher than the WHO ideal ranges. Unfortunately, the parameters such as the percentage of prescribing with generic name and from essential drug list was far more behind the optimal range.

The reno-protective effects of atorvastatin in crush syndrome and rhabdomyolysis:is there a dilemma?

Background/aim: We aim to determine the effects of low-dose atorvastatin treatment together with crush fluid resuscitation on renal functions and muscle enzyme levels in a rat model of crush syndrome. Materials and methods: The study involved female Wistar Albino rats weighing 250-300 g that were housed with free access to food and water. The crush model was obtained by compression. Rats were randomly divided into four groups: control (C) group, atorvastatin + crush fluid (ACF) group, crush fluid (CF) group, and hypertonic saline (%3) + mannitol + sodium bicarbonate (SM) group. Blood was obtained at 24, 48, and 72 h, and serum creatinine kinase, myoglobin, urea, creatinine, and lactate dehydrogenase levels were studied.Results: All parameters were statistically significantly higher in the control group than in the treatment groups at all hours. However, there was no statistically significant difference among treatment groups regarding any of the parameters.Conclusion: This is the first study determining the role of atorvastatin in the treatment of renal ischemia/reperfusion injury in a crush syndrome and rhabdomyolysis model setting. Larger studies with different atorvastatin doses are required to define the role of this drug in the treatment of renal ischemia/reperfusion injury during crush syndrome.

Captopril protects against burn-induced cardiopulmonary injury in rats.

BACKGROUND: This study was designed to determine the possible protective effect of captopril treatment against oxidative damage in heart and lung tissues induced by burn injury. METHODS: Under ether anesthesia, the shaved dorsum of Wistar albino rats was exposed to 90°C water bath for 10 seconds. Captopril was administered intraperitoneally (10 mg/kg) after the burn injury and repeated twice daily. In the sham group, the dorsum was dipped in a 25°C water bath for 10 seconds. At the end of the 24 hours, echocardiographic recordings were performed, then animals were decapitated and heart and lung tissue samples were taken for the determination of tumor necrosis factor-α (TNF-α) as a pro-inflammatory cytokine, malondialdehyde and glutathione levels and myeloperoxidase, caspase-3, and Na+,K+-ATPase activity in addition to the histological analysis. RESULTS: Burn injury caused significant alterations in left ventricular function. In heart and lung tissues, TNF-α and malondialdehyde levels and myeloperoxidase and caspase-3 activities were found to be increased, while glutathione levels and Na+, K+-ATPase activity were decreased due to burn injury. Captopril treatment significantly elevated the reduced glutathione level and Na+, K+-ATPase activity, and decreased cytokine and malondialdehyde levels and myeloperoxidase and caspase-3 activities. CONCLUSION: Captopril prevents burn-induced damage in heart and lung tissues and protects against oxidative organ damage.

nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril.

OBJECTIVE: To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril. METHODS: Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90°C (burn) or 25°C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was studied in brain areas by immunohistochemistry. RESULTS: There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups. nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p<0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p=0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p<0.05). CONCLUSIONS: Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain.

The effect of captopril on brain apoptosis after burn injury in rats.

AIM: The purpose of this study was to determine the possible protective effects of captopril treatment against apoptosis in the brain induced by burn injury. MATERIAL AND METHODS: Under ether anaesthesia, Wistar albino rats (200-250 g) were exposed to a 900C (burn) or 250C (sham) water bath for 10 s. The ACE group was treated with i.p. 10 mg/kg captopril immediately after burn injury and this treatment was repeated twice daily. At the end of the 24 hours, brain samples were taken. Apoptotic brain cells marked by terminal deoxynucleotidyl transferase-mediated d-UTPnick end labeling (TUNEL) were evaluated in the cerebellum and midbrain of rats. RESULTS: Apoptotic cells in the cerebellum were significantly decreased after captopril treatment and found to be lower when compared to the burn group (p < 0.001). In the midbrain of rats, the numbers of TUNEL-positive cells and apoptotic bodies were significantly increased in the burn group when compared to the control group (p < 0.001). The burn-induced changes were reduced in the captopril-treated burn group (p < 0.01). CONCLUSION: Captopril has beneficial effects in burn injury and should be assessed as a therapeutic agent in the management of this condition.