Analysis of Novel Anticoagulants for Atrial Fibrillation – Pharmacokinetics and Pharmacological Considerations.

Atrial Fibrillation (AF) is the most common arrhythmia. AF is a major risk factor for stoke. Warfarin has been available for more than 60 years and until recently it was the only oral anticoagulant used for the prevention of stroke. Despite the extensive studies and proven efficacy, its utility is limited by multiple factors. Warfarin interacts with a multitude of drugs and foods, has a delayed onset of action, has a narrow therapeutic range, requires routine lab monitoring and exhibits variable responses in patients. The novel agents dabigatran, rivaroxaban and apixaban have the potential to have some of the limitations of warfarin. This article will discuss the pharmacokinetic and pharmacological considerations and different characteristics of the novel anticoagulants when used for the prevention of AF.

The effect of angiotensin II receptor blocker on peritoneal membrane transports in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The objective of this study was to examine the effects of angiotensin II receptor blocker (ARB), used as an antihypertensive medication, on peritoneal membrane transporters in continuous ambulatory peritoneal dialysis (CAPD) patients. MATERIAL AND METHOD: Prospective and cross-over experimental study of peritoneal membrane transporters was conducted in 7 CAPD patients with hypertension. All previous antihypertensive drugs had been replaced by candesartan at the dose of 8-16 mg/day to control blood pressure below 140/90 mmHg. Hydralazine, which has no effect on peritoneal membrane transports, was added if the target blood pressure was not achieved. All patients had received candesartan for 12 weeks, then, were retreated with the previous antihypertensive drugs for another 6-week period. The modified peritoneal function tests assessing peritoneal membrane transports were performed at 1) baseline, 2) 6 weeks, 3) 12 weeks following candesartan treatment, and 4) 6 weeks after candesartan withdrawal. RESULTS: The blood pressure target was achieved in all patients and was not different among the 4 periods. The albumin clearance and 4-hour albumin loss were significantly decreased following candesartan treatment (p < 0.05). Both values returned to the high baseline levels after 6 weeks of candesartan withdrawal. There were no significant changes in net ultrafiltration and various small and large solute transports. No adverse effects, including hyperkalemia or increased erythropoietin dosage, had been observed. CONCLUSION: In hypertensive CAPD patients, candesartan could provide nutritional benefit by attenuating peritoneal loss of albumin and provides an effective antihypertensive action. Furthermore, candesartan does not impair other solute transports and net ultrafiltration.

Metabolic disposition of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl] carbonyl]-1-H-benzimidazol-2-yl] carbamate in hamsters: a study to understand chemoprophylactic action against experimental Ancylostomiasis.

Methyl [5-[[4-(2-pyridinyl-1-piperazinyl] carbonyl]-1H- benzimidazol-2-yl] carbamate (CDRI Compound 81-470) exhibits a long prophylactic action against experimental ancylostomiasis, when given parenterally but not orally. To find out an explanation for such a behaviour, metabolic disposition studies were performed in hamsters using [3H] compound 81-470. Following intramuscular administration, the compound was found to form a depot at the site of injection and to remain there in substantial amount for more than 7 weeks. The compound was fairly distributed in all the organs studied and the presence of radioactivity could be easily detected up to 7 weeks of observation period. The compound was very slowly eliminated from the body and only 38% of the radioactivity could be recovered in the urine and faeces during 14 days. The oral dose, to the contrary, was poorly absorbed and more than 62.8% was excreted in the faeces within 48 hr. Consequently, this dose yielded lesser area under plasma curve. More than 95% of the oral dose was eliminated within a week and hardly and radioactivity could be detected in the tissues after day 14. In accord with this pattern, in blood also the im dose was detected up to 7 weeks while the orally given compound reached undetectable level within 6 days only. The lower clearance and prolonged stay in the body of the im dose compared to quick elimination of the oral dose may be responsible for the long chemoprophylactic action of compound 81-470 when given through im route.

Diagnóstico in vitro de Haemonchus contortus resistente al albendazol, fenbendazol, oxfendazol y febantel en tres rebaños ovinos Tabasco o Pelibuey / In vitro diagnosis of resistant Haemonchus contortus to benzimidazoles in three flocks of Tabasco or Pellibuey breed sheep

El objetivo del estudio fue: a) detectar mediante una prueba in vitro, poblaciones de nematodos resistentes a bencimidazoles y prodencimidazoles en ovinos de raza Tabasco o Pelibuey y b) determinar los factores de manejo de animales y antihelmínticos que contribuyeron a la selección de los nematodos resistentes. La prueba in vitro básicamente puso en contacto huevos de H. contortus con diferentes concentraciones en ppm de tiabendazol; los resultados se sometieron a análisis Probit. El índice de resitencia alcanzado por las tres poblaciones de nematodos resistentes fue: 21.6, 17.5 y 19.2. Los factores que contribuyeron a la selección de nematodos fueron: sobrepastoreo, dosis subletales y carencia de refugio larvario. Los antihelmínticos involucrados son: albendazol, fenbendazol, oxfendazol y fabantel.