Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Apr 2015
Improved anti-emetic efficacy of 5-HT3 receptor antagonists in cancer patients with genetic polymorphisms of ABCB1 (MDR1) drug transporter.
Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect decreasing quality of life in patients with cancer. Genetic variations among patients may be responsible for part of the lack of efficacy of anti-emetic drugs. The aim of this study was to investigate how the genetic variants of the drug transporter ABCB1 (MDR1) gene affect anti-emetic treatment with 5-HT3 receptor antagonists. ⋯ No significant change was found between the total control rates among genotypes in the delayed phase. Each of three 3435TT, C1236TT, 2677TT genotypes of ABCB1 and their combination was associated with about 50% higher anti-emetic response to 5-HT3 receptor antagonists in the acute phase of chemotherapy in patients with cancer receiving moderately or highly emetogenic chemotherapy. ABCB1 (MDR1) genotypes may contribute to predict the anti-emetic efficacy of 5-HT3 antagonists.
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Basic Clin. Pharmacol. Toxicol. · Apr 2015
Comparative StudyA comparison of the reactivating and therapeutic efficacy of two newly developed oximes (k727 and k733) with oxime k203 and trimedoxime in tabun-poisoned rats and mice.
The reactivating and therapeutic efficacy of three original bispyridinium oximes (K727, K733 and K203) and one currently available oxime (trimedoxime) was evaluated in tabun-poisoned rats and mice. The oxime-induced reactivation of tabun-inhibited acetylcholinesterase was measured in diaphragm and brain of tabun-poisoned rats. The results showed that the reactivating efficacy of two recently developed oximes (K727 and K733) does not achieve the level of the reactivation of tabun-inhibited acetylcholinesterase induced by oxime K203 and trimedoxime. ⋯ The therapeutic efficacy of all oximes studied roughly corresponds to their reactivating efficacy. While both recently developed oximes were able to reduce acute toxicity of tabun less than 1.5-fold, another original oxime K203 and commonly used trimedoxime reduced the acute toxicity of tabun almost two times. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of oxime K203 and trimedoxime, and therefore, they are not suitable for their replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning.
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Basic Clin. Pharmacol. Toxicol. · Apr 2015
Randomized Controlled TrialIntravenous lipid emulsion given to volunteers does not affect symptoms of lidocaine brain toxicity.
Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject-blinded and two-phase cross-over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid(®) (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. ⋯ There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un-entrapped lidocaine area under concentration-time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.
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Basic Clin. Pharmacol. Toxicol. · Apr 2015
ReviewDiagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines.
The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. ⋯ Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2 -agonist or anticholinergic or both).