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Tacrine efficacy in Lewy body dementia.

BACKGROUND: Response to tacrine varies among patients with Alzheimer's disease (AD). Lewy body dementia (LBD) could be a high responder subtype of AD. The aim of the study was to compare the effects of tacrine in LBD and AD. METHODS: Seventy-five consecutive outpatients with mild or moderate AD were screened. Tacrine was given at a dose of 40 mg/day during 6 weeks. During the next 6 weeks, the patients were treated with 80 mg/day and afterwards with 120 mg/day. Patients were assessed at baseline and treated with a dose of 120 mg/day tacrine for 2 weeks. RESULTS: Analysis was performed on 39 patients (AD, N = 20; LBD, N = 19). Eight patients were lost to follow-up, eight patients manifested with side-effects, six suffered from an intercurrent somatic disease during the study and 14 patients had poor compliance or were treated with incompatible drugs. Twenty-two patients (11 AD/11 LBD) increased their cognitive performances with tacrine. Among the 22 patients, the improvement differed between the AD and the LBD groups. In AD, conceptualization improved; in LBD, the improvements occurred in verbal initiation and digit span. CONCLUSION: This study emphasizes the importance of using appropriate tests to determine the positive effects of pharmacological treatments.

Aged↗

Stabilizing effect of inorganic phosphate salts on antibiotic-steroid ophthalmic preparations.

Drocinonide phosphate potassium forms an insoluble complex with neomycin sulfate in aqueous solution. Dibasic sodium phosphate can be employed in an ophthalmic formulation to prevent the formation of this precipitate without affecting the stability of the steroid or the bioactivity of the antibiotic. Other phosphate steroid salts behaved in a like manner.

Chemistry, Pharmaceutical↗

Solid-state decomposition of alkoxyfuroic acids in the presence of microcrystalline cellulose.

A solid-solid interaction between alkoxyfuroic acids and microcrystalline cellulose has been studied. The decomposition of the mixture differs from that of the drug(s) alone, in that carbon monoxide (not carbon dioxide) is the high-temperature decomposition product. A model is proposed in which interaction occurs at contact points. A liquid decomposition product, dissolving part of the alkoxyfuroic acid (to the extent of its solubility) serves as a carrier, so that the number of contact points increases, thus accelerating the reaction. Both the main and ancillary parameters have calculated values that are consistent with the model.

Cellulose↗

Bisantrene solubility and skin toxicity studies: efficacy of sodium bicarbonate as a local ulceration antidote.

Bisantrene solubility and skin toxicity were studied in mice given intraperitoneal (IP) and intradermal (ID) drug respectively. Bisantrene (1 mg/ml) in 5% dextrose readily precipitated in the mouse peritoneum. The admixture of bisantrene into various lipophilic solvents did not reduce drug precipitation in vivo in the mouse or in vitro in human plasma at 37 degrees C. Drug stability studies using high performance liquid chromatography (HPLC) showed markedly reduced bisantrene stability at alkaline pH. Bisantrene skin toxicity in BALB/c mice was characterized by ulceration which persisted for up to four months after ID injection. Skin toxicity was consistently reduced by dilute sodium bicarbonate injection into the bisantrene extravasation site. Three clinical extravasation cases treated with sodium bicarbonate showed no bisantrene ulceration. Ineffective local antidotes included sodium cromolyn, N-acetylcysteine, hydrocortisone, and heat (which appeared to increase toxicity).

Aged↗

Effect of glucose 5% solution and bupivacaine hydrochloride on absorption of sufentanil citrate in a portable pump reservoir during storage and simulated infusion by an epidural catheter.

The stability of sufentanil (5 micrograms/ml as citrate) in admixtures with glucose 5% or bupivacaine hydrochloride (2 mg/ml) in 100 ml polyvinyl chloride portable pump reservoirs was investigated during simulated infusion by an epidural catheter at 32 degrees C for 48 h and during storage at 4 degrees C and 32 degrees C for 30 days. During both experiments a small decrease (< 5%) in concentration of sufentanil and bupivacaine was observed. No loss of sufentanil or bupivacaine could be detected (in both experiments) in the portable pump reservoirs when stored at 4 degrees C for 30 days. A significant decrease of sufentanil was observed when stored at 32 degrees C after 30 days when diluted with glucose (9.2%) or in combination with bupivacaine (8.9%); also, the bupivacaine concentration decreased significantly (4.1%). It is concluded that sufentanil in portable pump reservoirs can be used under patient conditions at 32 degrees C for 7 days when diluted with glucose 5% or 3 days in combination with bupivacaine hydrochloride.

Absorption↗

Compatibility of bupivacaine and iohexol in two mixtures for paediatric regional anaesthesia.

The compatibility of bupivacaine (0.25% and 0.125% wt/vol) with iohexol 300 mg I/ml was investigated. At room temperature bupivacaine does not decompose in these mixtures over a period of 24 h. pH Values (7.10 and 7.33), clarity, osmolality (370 and 379 mOsm/kg) and buffer capacity (0.035 ml and 0.010 ml 0.1000 mol/l NaOH per 10 ml) meet requirements for epidural injection. Both mixtures are suitable for epidurography.

Anesthesia, Conduction↗

[Drug interactions and the anesthesiologist].

Modern anesthesiology employs the combined administration of several drugs belonging to different pharmacological classes. Additionally, anesthesiologists are facing the challenge of polypharmacy regimens utilized by patients considered for surgical treatment When drugs are combined, the pharmacological effect may considerably differ from the individually expected properties. This may be beneficial or potentially lead to adverse drug reactions harming the patient. The incidence of drug interaction increases exponentially with the number of drugs administered. Depending on the mechanism involved, drug interactions can be classified as pharmaceutical, pharmacodynamic, or pharmacokinetic. Although there are enormous possibilities for adverse drug reactions nd the complexity is hard to identify, prediction of drug interaction is possible. Besides recognizing the general risk factors, fundamental knowledge of basic and clinical pharmacology is important to prevent serious or fatal drug interactions before they occur.

Anesthetics↗

In vitro polyvinylformaldehyde particle compatibility with chemotherapeutic drugs used for chemoembolization therapy.

PURPOSE: Because the effects of pirarubicin and carboplatin on the physical structure of particles made from polyvinylformaldehyde are not well known, we describe an experiment to test the in vitro polyvinylformaldehyde particle compatibility with these drugs used for chemoembolization of bone metastases. MATERIALS AND METHODS: Polyvinylformaldehyde particles (Ultra-Drivalon) were mixed in vitro with either pirarubicin or carboplatin as experimental samples, and with distilled water as control samples, and left for 24 h at 37 degrees C. The particles used measured 150-250 microm and 600-1000 microm in diameter. Particle morphology, including appearance, overall shape, and surface characteristics were examined using a microscope equipped with a videocamera. Particle size was measured by granulometry. Qualitative and quantitative variables were analyzed using, respectively, the two-sided Fisher's exact test and the Wilcoxon signed rank test for paired values, with a significance level of 0.05. RESULTS: No broken particles or microscopic degradations in the appearance, overall shape, or surface characteristics of any particles were observed. The particle size distribution was not significantly different between the experimental samples containing pirarubicin or carboplatin and the control sample of particles with diameters in the same range. CONCLUSION: Particles made from polyvinylformaldehyde can be mixed with pirarubicin or carboplatin without any risk of damaging their physical properties.

Antineoplastic Agents↗

Drug interactions in the treatment of Parkinson's disease.

In recent years, the antiparkinsonian drug regime has become increasingly complicated. A wide range of antiparkinson agents is meanwhile available. Combination therapies may unfortunately induce interactions up to the point of life-threatening events. The potential of drug-drug interactions must be taken into account before starting a patient on combination treatment. Moreover, the frequent multimorbidity of patients with Parkinson's disease necessitates the application of additional drugs. A general overview is difficult to maintain because of the countless number of possible interactions. Cautious proceeding is certainly indicated in particular cases. The most common interactions will be discussed below. We should bear in mind that many of the interactions related to drug combinations are unknown yet.

Antiparkinson Agents↗

Prescription errors with cytotoxic drugs and the inadequacy of existing classifications.

OBJECTIVE: To quantify the amount of potential prescription errors for anticancer drugs in order to improve the quality of care. SETTING: The cytotoxic reconstitution unit at the Laennec Hospital in Paris, France during 6 months in the year 2000. METHOD: Pharmacist carried out a systematic analysis (e.g. dose, protocol, physicochemical properties) of the prescriptions for anticancer drugs (ACDs) before the compounding and handling at the cytotoxic unit of the pharmacy took place. The detected errors and potential errors were documented and analysed. MAIN OUTCOME MEASURE: Numbers and kinds of medication errors. RESULTS: Documenting data was difficult because of the inadequacy of existing classifications that usually do not include potential errors in prescriptions for with ACDs. Despite the presence of a formulary on the clinical wards, 349 errors were detected and documented, mainly concerning pharmaceutical aspects. Physicians were not aware of this type of errors due to lack of studies about their impact. Teaching aids such as a computer program for prescribing and production of ACDs could help in minimising these errors. CONCLUSION: The 349 detected errors involved mainly the physicochemical properties of preparations. A computerised prescription network could possibly reduce the number of such errors. Furthermore, a redefinition of the classifications of errors for cytotoxic preparations seems desirable, and such classifications should include typical pharmaceutical problems, and potential errors that do not reach the patient.

Antineoplastic Agents↗

Effect of nystatin and chlorhexidine digluconate on Candida albicans.

Polyene antibiotics such as nystatin and amphotericin B are among the most widely recommended drugs for use against oral candidiasis. It is also generally accepted that chlorhexidine gluconate is an appropriate adjunct or an alternative to specific antimycotic drugs. The aim of the present study was to examine the effect of the combination of nystatin and chlorhexidine digluconate on Candida albicans in vitro. The minimum inhibitory concentration (MIC) value for the combination of the two drugs was found to be significantly higher than the values for each of the drugs alone, approximately 33 times the MIC value for the nystatin solution and 4 times the value for chlorhexidine digluconate. The results of the MIC study and the presence of a precipitate in all combinations of nystatin and chlorhexidine digluconate showed that the combination of the drugs is not effective in vitro against Candida albicans. The most likely reason is that a low solubility chlorhexidine-nystatin salt is formed, thus rendering the combined drug complex ineffective as an antibiotic agent.

Candida albicans↗

Stability and compatibility of a mixture of the anti-cancer drugs etoposide, cytarabine and daunorubicine for infusion.

We evaluated (i) the stability of a mixture of the three anti-cancer agents used for the treatment of leukemia, namely etoposide, cytarabine and daunorubicine, in 5% glucose, and (ii) its compatibility towards various materials during an infusion protocol as performed for therapeutic purposes in hospital practice. Etoposide and cytarabine were assayed by high-performance liquid chromatography with a C18 type column and UV detection. Daunorubicine was assayed by visible spectrophotometry. The stability study showed all three anti-cancer drugs to be stable in 5% glucose solution, both alone and mixed. Best conservation was obtained by keeping bottles containing the mixture in the dark at room temperature. During the infusion protocol used in clinical practice, etoposide, cytarabine and daunorubicine were stable and compatible with the various materials present in the infusion sets and extension tubing (polyvinyl chloride, polyethylene) and catheters (silicone). Observed variations in concentration did not exceed 10% of initial concentrations of each drug, though we would advocate changing infusion sets and extension tubing daily.

Antineoplastic Combined Chemotherapy Protocols↗