Pharmazie
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Review Meta Analysis
Duration of dual antiplatelet therapy after percutaneous coronary intervention with implantation of second-generation drug-eluting stent: A meta-analysis of randomized controlled trials.
Objective: The optimal duration of dual antiplatelet therapy (DAPT) in patients after PCI with implantation of a drugeluting stent is still controversial. We conducted a meta-analysis to compare the efficacy and safety of short term DAPT (≤ 3 months) followed by P2Y12 inhibitor monotherapy and standard DAPT (12 months) after PCI. Method: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until November 2019. ⋯ There were no significant differences in all-cause death [OR=0.91, 95%CI:0.71-1.16, P =0.45], major adverse cardiac and cerebrovascular event [OR=1.01, 95%CI:0.87-1.17, P =0.91] and stent thrombosis [OR=0.97, 95%CI:0.61-1.54, P =0.91] between with the short term DAPT group and the standard DAPT group. Conclusions: Short term DAPT followed by P2Y12 monotherapy could reduce the risk of bleeding without increasing the incidence of ischemic events after PCI with implantation of second-generation DES compared with standard DAPT. Therefore, short term DAPT may be a promising strategy to balance ischemic events and bleeding complications in patients after PCI.
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This paper summarizes recent developments in the field of soft drug development as collected and reviewed for the 9th Retrometabolism-Based Drug Design and Targeting Conference. Soft drugs are still often confused with prodrugs because they both require metabolic transformations; however, they are conceptual opposites: whereas, prodrugs are pharmacologically inactive and are converted by a predictable mechanism to the active drug, soft drugs are active therapeutic agents as such and are designed to undergo a predictable and controllable metabolic deactivation after exerting their desired therapeutic effect. Several rationally designed soft drug examples including clinically approved ones (e.g., clevidipine, esmolol, landiolol, loteprednol etabonate, and remifentanil) as well as others that have reached clinical investigations within different therapeutic areas (e.g., budiodarone, naronapride, remimazolam, tecarfarine) are briefly summarized. ⋯ Several new initiatives (e.g., MOC-etomidate, AZD3043) are focused in this area; they are also briefly reviewed. Finally, just as there are many 'accidental' prodrugs, there are 'accidental' soft drugs too: i.e., therapeutics that were not intentionally designed to be soft drugs, but turned out to be essentially soft drugs. Some examples, such as articaine or methylphenidate, are briefly reviewed.
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Review
Allergic rhinitis: meaningful and less meaningful combination treatments including reminiscences.
Allergic rhinitis (AR) results from a complex allergen-driven mucosal inflammation in the nasal cavity. Current guideline-based therapy for allergic rhinitis include oral and nasal antihistamines, topical and systemic glucocorticoids, decongestants, antimuscarinic agents, mast cell stabilizing drugs, leukotriene-receptor antagonists, and others. In spite of guideline recommendations, most patients are using multiple therapies in an attempt to achieve symptom control. ⋯ Recently, a novel fixed dose combination containing azelastine and fluticasone propionate has successfully been introduced. At present, it represents the only meaningful topical drug combination. Perhaps, it will be followed by others.
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Substituting generic formulations of the same chemical agent is a common practice in German health care on the basis of so called rebate contracts. The substitution of a medication may affect the patients' adherence or result in adverse events. While adverse events which may be caused by the pharmacological activity of the agent itself can be explained, some non-specific side effects cannot be substantiated referring to pharmacological factors. ⋯ But up to 34% of patients being treated for psychological diseases confronted with a change of their medication had additional adverse events. On the basis of the studies analysed, the conclusion can be drawn that the nocebo effect can play a crucial role in the treatment of psychological diseases. Therefore, physicians and pharmacists should be responsible to prevent the nocebo effect through adequately educating the patients.
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Microdialysis (MD) has become one of the major tools to sample endogenous and exogenous substances in extracellular spaces. It is more suitable for pharmacokinetic-pharmacodynamic (PK-PD) studies than other techniques. ⋯ It can be concluded that MD offers an unique opportunity, to study simultaneously pharmacokinetic (PK) behavior of a drug and its effect on the extracellular levels of endogenous compounds, which may facilitate proof-of-concept demonstrations for target modulation, enhance the rational selection of an optimal drug dose and schedule. In addition, MD/PK-PD can also minimize uncertainties associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development.