[Drug interactions in an elderly population. Prospective assessment of their frequency and seriousness among 56 patients]. / Interactions médicamenteuses dans une population âgée.

OBJECTIVE: To assess the nature and the number of potential adverse drug interactions by analysis of outpatient prescriptions for elderly patients, of medications taken during the week before hospitalization in a general surgery department. METHOD: The study of 56 patients older than 65 years was conducted from November 2002 through February 2003. The outpatient prescriptions corresponding to medications taken during the 7 days before admission were analyzed by a pharmacy resident, who used data-processing tools and databases. RESULTS: Most patients (83%) knew the reason for their prescription. Thirteen (28%) reported using over-the-counter medication. Only 89% of the patients reported complete compliance with the prescription. The average age of the patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6 drugs (range: 2-10) per prescription. The average number of possible interactions was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions. The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible adverse interactions (55%). No contraindication was noted. The drugs mentioned most often were benzodiazepines, diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, and beta-blockers. The potential risks most often found were hypotension, depression of the central nervous system, hypoglycemia and acute renal failure. The drug interactions were mainly due to the accumulation of the effects of separate drug classes. Deterioration in renal function was often noted as plasma concentration of the second drug increased. DISCUSSION: This exploratory study shows the reality of the iatrogenic risk for elderly patients. This analysis of outpatient prescriptions is consistent with findings in the literature. Analysis of interactions is conducted on a pairwise basis. It is thus difficult to envisage the consequences of the association of 5 or more drugs in patients with complex illnesses and diminished physiological and metabolic capacity. Patient files kept by the pharmacist could provide information about individual combinations ofthe prescription and over-the-counter drugs.

Stability of doxorubicin combined with Radioselectan, a contrast agent, for chemoembolization.

OBJECTIVE: To assess the stability of doxorubicin combined with Radioselectan. METHODS: Solutions of doxorubicin 5 mg/mL were prepared from commercially available 50 mg powder with 10 mL of Radioselectan. They were stored in glass syringes at 4, 25 and 45 degrees C. The concentrations of doxorubicin were determined using a stability-indicating high-performance liquid chromatography method. The initial and final pHs of solutions were compared. The times (t90) needed for doxorubicin to fall to 90% of its initial concentration were calculated by a linear regression analysis. RESULTS: The t90 [95% confidence limits] were 79 [75-83], 56 [53-59] and 22 [21-23] hours for the solutions stored at 4, 25 and 40 degrees C respectively. The initial pH of the solutions stored at 4, 25 and 40 degrees C were 6.52, 6.50 and 6.51 respectively. The final pH of solutions stored at 25 and 40 degrees C decreased significantly by 0.3 and 0.9 respectively. No change of pH solution stored at 4 degrees C was observed. CONCLUSION: Doxorubicin combined with Radioselectan stored at room temperature is stable for 48 h.

Fenoverine-induced rhabdomyolysis.

Fenoverine is a spasmolytic drug that inhibits calcium channel currents. We describe the clinicopathologic findings in two patients with fenoverine-induced rhabdomyolysis, of whom one died. A transient left-bundle-branch block was observed in both patients. In one case, pre-existing hepatic dysfunction may have induced accumulation of the drug. Concurrent treatment by fibrates, as observed in the second patient, may have been a predisposing factor for fenoverine-induced rhabdomyolysis. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of the drug in patients with hepatopathy or those being treated with cholesterol-lowering agents. Physicians should be aware of life-threatening adverse effects of apparently innocuous drugs.

Optimal handling of blood samples for routine measurement of lactate and pyruvate.

Blood lactate and pyruvate are of critical importance for the diagnosis of mitochondrial diseases. To determine guidelines for adequate blood pyruvate and lactate determinations, intraindividual studies were carried out on 10 subjects, and the influences of venostasis, delay before deproteinization, and pH in the pyruvate assay were analyzed. Delays of 1 hour or more before deproteinization of samples induced major elevations of lactate-pyruvate ratios. The lactate-pyruvate ratio correlated positively with pH in the pyruvate assay, and inadequate pH appeared as a largely underestimated cause of misleading results, while venostasis was a minor source of errors.

Determination of fenoverine in tissue samples by high-performance liquid chromatography.

Fenoverine is a spasmolytic, non-anticholinergic phenothiazine derivative that inhibits calcium channel currents. We describe a high-performance liquid chromatographic method for the determination of fenoverine in striated muscle, smooth muscle, myocardium, and liver tissue. Reversed-phase liquid chromatography was performed on a 5 microns Nucleosil C18 column with acetonitrile-0.015 M phosphate buffer (28:72, v/v) as a mobile phase and detection with ultraviolet at 214 nm. The limit of quantitation of fenoverine in tissue samples was 25 ng injected. This method is well suited for the determination of fenoverine in various organs in animal experiments.

Open trial of tacrine therapy in 70 HIV-infected patients.

The purpose of this study consisted in following-up the biological and clinical parameters in HIV infected patients treated with tacrine (THA). THA (150-300 mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty-five were treated after discontinuation of AZT treatment and 35 as a first intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell count by more than 50% relative to pretreatment levels and fifteen (21%) showed an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight of the twenty-seven patients who were initially positive, and decreased by 25 and 50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80% of the patients. From a clinical point of view, there were two deaths (3%) and five opportunistic infections (7%). The treatment with THA was stopped in five patients because of side effects (nausea, rash). Neither hepatotoxicity, hematotoxicity, nor pancreatitis was observed during the THA treatment. In group II and III only two patients (6%) developed an opportunistic infection.