RESUMO
BACKGROUND AND AIMS: Due to the increasing number of hepatitis C virus (HCV)-infected patients being treated with direct antiviral agents (DAAs) in Romania, we aimed to conduct a pharmacovigilance study in order to comprehensively evaluate the safety profile for the ombitasvir/paritaprevir/ritonavir and dasabuvir (Om/Pa/Ri+Da) regimen. METHODS: A retrospective analysis was conducted on the individual case safety reports (ICSRs), extracted from VigiBase® on 1 st February 2018, which included the Om/Pa/Ri+Da regimen as suspected for causing adverse drug reactions (ADRs). Potential drug-drug interactions (DDIs) were checked for all concomitant medication using the IBM Micromedex® tool. RESULTS: Among the 1,102 ICSRs retrieved, 260 were serious (23.5%). Ribavirin was significantly associated with more ADRs reported per case (on average 5.1 vs. 3.2 ADRs/case, p<0.001). Most commonly reported ADRs were pruritus (6.8%), fatigue (5.4%), dizziness (4.3%) and headache (3.8%). For the serious ICSRs, a significant relationship was found between age and renal and urinary disorders, and between gender and neoplasms, injury, poisonings and procedural complications. Hepatotoxicity was identified in six ICSRs, four of them being serious. Potential contraindicated DDIs were identified in 1.9% of all ICSRs and major DDIs in 20.4%. CONCLUSIONS: About a third of the ICSRs related to Om/Pa/Ri+Da regimen were serious. Pruritus, fatigue, dizziness and headache were the most commonly reported ADRs. The frequent use of multiple co- medications in HCV-infected patients requires the consideration of potential DDIs when using the Om/ Pa/Ri+Da regimen.
RESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole derivatives 5aâ»l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g, 5i, 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.
Assuntos
Analgésicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Edema/tratamento farmacológico , Imidazóis/síntese química , Tiadiazóis/síntese química , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina/efeitos adversos , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Edema/induzido quimicamente , Feminino , Imidazóis/administração & dosagem , Imidazóis/química , Imidazóis/farmacologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Tiadiazóis/administração & dosagem , Tiadiazóis/química , Tiadiazóis/farmacologiaRESUMO
BACKGROUND AND AIMS: Resistant hypertension is defined as failure to achieve blood pressure lower than 140/90 mmHg when using three antihypertensive agents or controlled blood pressure with four or more drugs. We aimed at assessing the prevalence of resistant hypertension and to describe a type 2 diabetes population with resistant hypertension. METHODS: The retrospective observational study included (n=73) type 2 diabetes subjects with resistant hypertension selected from (n=728) subjects admitted to the Centre of Diabetes, Cluj, Romania. RESULTS: The subjects (70% women) had a mean age of 65.0±8.9 yrs. and diabetes duration 11(6-19) yrs. Prevalence of resistant hypertension was 10%. Chronic diabetes complications and cardiovascular disease were present in 77% and 56% of subjects respectively. On admission, antihypertensive drugs used were: angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers 93%, ß-blockers 88%, diuretics 78%, calcium channels blockers 59%, adrenergic α-antagonists 11%. Systolic and diastolic blood pressure were lower in the last compared to first admission day. Diuretics and calcium channels blockers were the most frequently newly added antihypertensive agents. CONCLUSION: Although the prevalence of resistant hypertension in type 2 diabetes did not differ from the general population, we observed that these patients had increased frequency of chronic diabetic complications. Angiotensin-converting enzyme inhibitors or angiotensin II receptors and ß-blockers were the most used antihypertensive drugs, while the most frequently newly prescribed drugs were diuretics and calcium channel blockers.
