In the present work, the antiglaucoma drug, acetazolamide, was formulated as microsponges in situ gel for ocular drug delivery aiming an improved therapeutic efficacy and reduction in the systemic side effects of oral acetazolamide. The microsponges were prepared by the quasi emulsion solvent diffusion method and were incorporated into 25% pluronic F-127 in situ gel. Ethyl cellulose polymer in different proportions with drug was used to prepare the microsponges. Different parameters were evaluated to select the best formulation. The formula S2 with drug to polymer ratio (2:1) showed high entrapment efficiency of about 82% and mean particle size of about 10 µm with polydispersity index (PDI) of 0.22, which are suitable characters for ocular delivery. The in situ gels were evaluated for physicochemical properties (pH, gelling capacity, gelation time and rheological properties) and in vivo studies. S2 formulation showed higher therapeutic efficacy compared to free drug in gel. It was non irritant to the rabbit's eye. These results indicated that acetazolamide microsponges in situ gel have potential ability for ophthalmic delivery.
The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72-0.94]), being a male patient (OR, 2.86 [95% CI, 1.05-7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07-0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28-10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered.
The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.
Background: Drug interactions continue to be an important cause of adverse effects, especially with cardiovascular drugs. Objective: This cross-sectional observational study aimed to recognize the frequency of potential drug-drug interactions (pDDIs) using three electronic knowledge bases (KBs); Lexicomp ® , Micromedex ® , and the free Drugs.com®, compare the inclusion and gradings of pDDIs in these three KBs and to identify associated risk factors. Methods: Medication orders of 125 patients in the cardiovascular department and its intensive care unit (ICU) of Assiut University Hospitals, Egypt were screened for pDDIs. Results: About 88.8% of the patients were prescribed five or more drugs. A sum of 1206 pDDIs was found which comprised of 245 different interacting pairs. Overall, 96.8% of the patients had at least
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