Yet Another Doctor Blog On The Internet

Extractive spectrophotometric determination of some anti-inflammatory agents with methylene violet.


There were 112 patients in the pre- and 115 patients in the post-program group. After implementation of the inpatient warfarin management program, obtaining baseline INRs increased from 74% to 90% (p=0.001). Orders for baseline CBCs increased from 85% to 94% (p=0.026). Obtaining CBCs every 3 days increased from 54% to 74%, (p<0.001). However, there was no significant change in orders for daily INRs (p=0.055). Education by nursing increased from 54% to 80%, (p<0.001), by pharmacy increased from 8% to 76%, (p<0.001), and by dietary increased from 11% to 79%, (p<0.001). Documentation by all three disciplines in each patient increased from 3.6% to 59%, (p<0.001). Significantly fewer patients received vitamin K and/ or fresh frozen plasma for supratherapeutic INRs with bleeding complications after the program was initiated compared to baseline (p=0.009).

Aprepitant is a known inducer of CYP2C9, the main warfarin-metabolizing enzyme. Consequently, co-administration of these two drugs may result in reduction of the anticoagulation activity of warfarin. However, the nature and degree of time-dependent changes in prothrombin time international normalized ratio (PT-INR) after aprepitant and warfarin co-treatment in patients receiving anticancer chemotherapy has not been elucidated. We retrospectively examined the changes in warfarin dose, PT-INR, and warfarin sensitivity index (WSI; average of PT-INR value/average of daily warfarin dose) during four weeks, i.e., one week before and three weeks after aprepitant administration. The mean and standard deviation values of WSI for one week before and one, two, and three weeks after the beginning of aprepitant administration were 0.51±0.22 (1.00, n=34), 0.74±0.30 (1.53±0.59, n=30), 0.38±0.15 (0.82±0.22, n=28), and 0.46±0.29 (0.87±0.23, n=24), respectively. Values in parentheses represent relative changes versus WSI of one week before and number of subjects. Although the mean value of WSI significantly increased one week after aprepitant administration compared to that at one week before the administration, it in turn significantly decreased two weeks after compared to one week before (paired t-test, p<0.05 after Bonferoni correction). In patients taking warfarin, PT-INR should be carefully monitored for at least two weeks after the beginning of aprepitant administration because it may fluctuate with both aprepitant and chemotherapy during this period.

Retrospective series (305 patients) undergoing TURP at a tertiary hospital between 2006 and 2010. All men were evaluated in preadmission clinics with defined protocols, with a low threshold for cardiovascular investigation. Incidence of postoperative bleeding and cardiovascular and cerebrovascular events was determined for 3 patient cohorts: group A--where anticoagulants were ceased preoperatively; group B--who were not receiving any anticoagulants; and group C--who underwent TURP while taking aspirin.

A total of 3766 case reports of drug interactions from 47 countries were identified. Of the 123 different drug combinations reported, 113 were described in the literature to interact. The mechanism of the drug interaction was categorised as pharmacodynamic (46 combinations; 41%), pharmacokinetic (28; 25%), a combination of both types (18; 16%) and unidentified (21; 19%). Pharmacodynamic drug interactions primarily concerned pharmacological additive effects, whereas enzyme inhibition was the most frequent pharmacokinetic interaction. The combinations reviewed primarily implicated drugs such as warfarin, heparin, carbamazepine and digoxin.

Warfarin has been the mainstay oral anticoagulant (OAC) medication prescribed for stroke prevention in atrial fibrillation (AF) patients. However, warfarin therapy is challenging because of marked interindividual variability in dose and response, requiring frequent monitoring and dose titration. These limitations have prompted the clinical development of new OACs (NOACs) that directly target the coagulation cascade with rapid onset/offset of action, lower risk for drug-drug interactions, and more predictable response. Recently, NOACs dabigatran (direct thrombin inhibitor), and rivaroxaban and apixaban (factor Xa [FXa] inhibitors) have gained regulatory approval as alternative therapies to warfarin. Though the anticoagulation efficacy of these NOACs has been characterized, differences in their pharmacokinetic and pharmacodynamic profiles have become a significant consideration in terms of drug selection and dosing. In this review, we outline key pharmacokinetic and pharmacodynamic features of each compound and provide guidance on selection and dosing of the 3 NOACs relative to warfarin when considering OAC therapy for AF patients. Importantly, we show that by better understanding the effect of clinical variables such as age, renal function, dosing interval, and drug metabolism (CYP3A4) and transport (P-glycoprotein), we might be able to better predict the risk for sub- and supratherapeutic anticoagulation response and individualize OAC selection and dosing.