[Pharmacogenomics in routine medical care]. / Pharmakogenomik in der Praxis.

Pharmacogenomics investigates inherited differences in drug responses including beneficial and adverse reactions. While a considerable amount of evidence for genetic influences on drug responses has been accumulated within the last decade, predominantly in small studies, its value in routine therapy is still a matter of debate. The aim of this review is to discuss well established examples where pharmacogenomic techniques can improve routine treatment. Examples include genotyping of CYP2D6 in the context of antidepressant therapy, analysis of TPMT variants for the prediction of mercaptopurine-induced bone marrow depression, VKORC1 and CYP2C9 analyses for a better control of anticoagulant administration and the SLCO1B1 variant in the context of statin-induced myopathies.

[Risks associated with drug therapy. What do patients need to know? What can they do]. / Risiken in der Arzneimitteltherapie: Was müssen Patientinnen und Patienten wissen? Was können sie tun?

BACKGROUND: Errors can occur at any time during drug therapy. A not inconsiderable percentage of hospital admissions to internal medicine departments are caused by adverse drug events (ADEs), many of which could be avoided. Avoidable ADEs mainly result from suboptimal procedures in the medication process. In order to recognize and minimize these risks, cooperative interaction of all those involved in the medication process is required. This also includes involving patients. A plan of action to improve safety of drug therapy in Germany has recently been completed under the aegis of the Federal Ministry of Health. In a concerted effort, structures and procedures of pharmacotherapy are to be systematically analyzed and improved. The plan of action is focused on measures that can be achieved in the short term, with particular emphasis on the reduction of risks. PURPOSE: The purpose of this paper is to make a contribution to increasing the patients' awareness for the risks associated with drug therapy and to provide suggestions of what they can do to improve the safety of their own therapy. CONCLUSION: With relatively simple means, patients can make an important contribution to improving the safety of drug therapy. However, only a collective increased sensitization for potential medication errors can lead to a sustainable risk reduction.

Fatal intoxications by acenocoumarol, phenprocoumon and warfarin: method validation in blood using the total error approach.

A simple high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection has been developed and validated for simultaneous identification and quantification of three antivitamin K drugs (acenocoumarol, warfarin and phenprocoumon) in whole blood. The aim of this development was to propose an analytical technique adapted to the situations of forensic toxicology, i.e. intoxication with massive anticoagulant doses, when the usual coagulation tests could not be used. The blood sample, after spiked with prazepam as an internal standard (IS), was submitted to a liquid-liquid extraction (LLE) prior to HPLC analysis. A chromatographic separation was achieved on a C8 Symmetry column with a mobile phase consisting of an acetonitrile and phosphate buffer (pH 3.8) mixture in a gradient mode. Detection was carried out at a wavelength between 200 and 400 nm. This method has been validated with the concept of total error as decision criterion. Trueness ranged from 99.1% to 105.0% and precision was good with RSD between 1.3% and 6.7%. Consequently, this rapid and simple chromatographic technique is well adapted to focus intoxications with most important coumarinic drugs available on pharmaceutical market and is now routinely used in our laboratory for forensic "general unknown" screening.

[Off-label use in long-term anticoagulation after liver transplantation due to phenprocoumon-induced hepatic failure]. / Off-Label-Use in der Langzeitantikoagulation nach Lebertransplantation wegen phenprocoumoninduzierten Leberversagens.

BACKGROUND: Drug therapy should be individualized according to criteria of efficacy, adverse effects, and treatment adherence. This is particularly important at the interface of inpatient and ambulatory care. Aspects of drug approval (labeling) and individual refunding by health care insurance should also be taken into account. CASE REPORT: A patient (male, 61 years, painter) showed elevated transaminases after treatment with phenprocoumon because of a deep vein thrombosis in 1999. Transaminases normalized completely after discontinuation of phenprocoumon. Other reasons for the elevated transaminases could be excluded. After a recurrent thrombosis in 2003 phenprocoumon was prescribed again followed by recurrent elevation of transaminases and subsequent cholestatic hepatitis progressing to fulminant hepatic failure that required liver transplantation. After transplantation the patient's general state of health was good and liver function nearly normal. Anticoagulation was indicated beyond the postoperative phase because of recurrent deep vein thrombosis and atrial fibrillation. A low-molecular-weight heparin was chosen for long-term treatment. CONCLUSION: A low-molecular-weight heparin appears to be the most appropriate way to maintain effective and safe anticoagulation in this patient. Coumarins carry a residual risk of an extrahepatic, immunologically mediated cross-sensitization. Long-term use of ximelagatran may also cause liver damage. For heparinoids, hirudins, and other drugs affecting coagulation like platelet aggregation inhibitors, therapeutic evidence is not sufficient. Though subcutaneous application of heparin is a disadvantage for the patient, therapeutic alternatives do not have better documented efficacy or less hepatotoxic potential. The low-molecular-weight heparin fulfills the criteria for refunding set by federal jurisdiction.