[Plasma levels of anti-arrhythmic drugs and clinical effectiveness in the treatment of ventricular arrhythmias].
D BracchettiF NaccarellaGuaragna RfM PalmieriAngelo BartolettiGaetano BarbatoMalini PlB. MarchesiniE Ambrosioni
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Abstract:
In spite of the ratio between plasmatic concentration and antiarrhythmic effects of a drug many factors can be influenced by many factors, the plasma level monitoring plays an important clinical role. The efficacy of the antiarrhythmic therapy should be evaluated not only by means of ECG-Holter monitoring and/or electrophysiological study but also by the means of determination of plasmatic and tissular concentration of a drug and metabolites. This latter is indispensable in the evaluation of new antiarrhythmic drugs and of a dose/effect relationship during acute and chronic therapy.Keywords:
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Anti-Arrhythmia Agents
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Unerwünschte Arzneimittelwirkungen (UAWs) gehören zu den wichtigsten Problemen einer Pharmakotherapie. UAWs können zu einer Erhöhung der Morbidität wie auch Mortalität beitragen, die Compliance vermindern, so den Therapieerfolg gefährden, und führen damit zu beträchtlichen direkten und indirekten medizinischen Folgekosten. Das frühzeitige Erkennen potentieller UAWs kann einen entscheidenden Einfluss auf den Schweregrad einer Reaktion haben. Dabei ist es wichtig zu differenzieren, ob die Reaktion im Rahmen des pharmakologischen Wirkprofils eines Arzneimittels erklärbar ist oder andere, z.B. immunologische oder genetische Faktoren, pathogenetisch eine Rolle spielen. Solche Überlegungen und die Etablierung eines kausalen Zusammenhanges mit der Medikation können bei der Planung der Weiterführung einer Therapie mitentscheidend sein. In der Mehrzahl der Fälle stehen UAWs im Zusammenhang mit den pharmakologischen Eigenschaften des Arzneimittels und sind damit zumindest potentiell vermeidbar. Eine auf die individuellen Bedürfnisse des einzelnen Patienten maßgeschneiderte Pharmakotherapie kann einen wichtigen Beitrag zur Verhinderung von UAWs leisten.
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Summary: Five commonly used antiarrhythmic agents are examined with regard to their pharmacokinetics, pharmacology, electrophysiology, and clinical utility. The effective, nontoxic plasma levels are noted, and important drug-drug interactions with these agents are noted. Monitoring plasma levels of these agents serves a useful function in that it identifies patients who are not compliant, who are taking too little drug, or who are taking too much drug. Current techniques do not allow rapid, reproducible, and inexpensive measurements of free (vs. bound) drug in the plasma, a quantity that is likely to be substantially more valuable in determining drug effect than total plasma concentration. Previous studies on drug effectiveness may not have taken into account natural fluctuations in arrhythmia frequencies that mimic drug effect.
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The irrational use of medication, by which we understand the administration of drugs for indications where their effectiveness has not been confirmed, the disregard of restrictions and warnings against their use, and the use of drug combinations which do not increase the therapeutic effect but to the contrary increase the risk of adverse drug reactions, is a serious problem encountered in paediatric pharmacotherapy. Each year the centres for monitoring of adverse drug reactions receive many reports, the analysis of which show that the reasons of occurrence of adverse drug reactions after drug administration, are specifically due to irrational use of medications. In order to prevent in an active way the occurrence, of adverse drug reactions following drug administration it is worthwhile to bring to attention the reasons for their occurrence which not infrequently bring about pathological effects. Our work which is based on reports received by the Regional Centre for Adverse Drug Reactions Monitoring in Krakow concerning the occurrence of adverse drug reactions in an attempt to bring to attention in our view important problems in current pharmacotherapy.
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Drug related problems represent an important problem in geriatric patients, and contribute to hospitalization in 15 to 30% of the admissions. In most cases this concerns adverse drug reactions (normal dose and overdose) but also drug therapy failures (e.g. undertreatment) are common. The main pharmacological classes involved are cardiovascular drugs and drugs for the central nervous system. Drug related problems can be prevented by regular medication review to decide if all drugs have to be continued, and to check for adverse drug reactions. Clinical pharmacists in hospitals can detect drug related problems (over-, under- and misuse using a systematic approach) and recommend changes to improve pharmacotherapy. The community pharmacist can help by elaborating drug schemes, by screening for medication interactions, and by resolving practical problems.
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