Polypharmacy-an Upward Trend with Unpredictable Effects.

BACKGROUND: Guideline-oriented treatments can lead to polypharmacy, i.e., the simultaneous long-term use of multiple drugs. Polypharmacy mainly affects elderly patients. The goal of this review is to survey the current scientific evidence about polypharmacy, focusing on clinical endpoints, and to point out implications for medical practice and research. METHODS: This selective literature review is based on pertinent publications that were retrieved by a selective search in PubMed employing the terms "polypharmacy AND general practice." Selected references were considered as well. RESULTS: In Germany, polypharmacy currently affects approximately 42% of persons over age 65, with an ongoing upward trend. 20-25% of these patients receive potentially inappropriate drugs. Approximately 86% of the daily doses of drugs taken by persons over age 65 are prescribed by general practitioners. There is inconsistent evidence on the question whether polypharmacy affects clinical endpoints such as mortality. It cannot be determined with certainty whether polypharmacy itself, or the underlying multimorbidity, is the reason for worse clinical outcomes. Lists, instruments, and guidelines such as PRISCUS (a list of potentially inappropriate drugs for elderly patients), FORTA (Fit fOR The Aged), MAI (the Medication Appropriateness Index), and the Hausärztliche Leitlinie Multimedikation (a German-language guideline on polypharmacy for general practitioners) can help physicians take care of patients who are taking multiple drugs. It has not yet been proven, however, that their use has any effect on clinical outcomes. CONCLUSION: The decision whether to keep giving a drug or to discontinue it must always be made individually on the basis of current treatment goals; drug lists and a pertinent general practitioners' guideline can be useful aids in decision-making. Efforts to pay more attention to multimorbidity and polypharmacy in future studies and guidelines are deserving of support.

Achieving the World Health Organization's vision for clinical pharmacology.

Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need.

[Rare cause for severe hypertriglyceridemia - case 9/2013]. / Seltene Ursache einer schweren Hypertriglyzeridämie - Fall 9/2013.

HISTORY AND ADMISSION FINDINGS: We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. INVESTIGATIONS: Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. DIAGNOSIS, TREATMENT AND COURSE: Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. CONCLUSIONS: Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment.

[Difficulties in adressing purging behaviour in the treatment of a patient with anorexia nervosa]. / Purging-Verhalten einer Anorexiepatientin: eine besondere Herausforderung.

HISTORY AND CLINICAL FINDINGS: We report on a 24-year-old patient with secondary amenorrhoea, underweight (BMI 15,0 kg/m²), and a fear of weight gain, who used laxatives, diuretics, excessive sport and human chorionic gonadotropin (hCG) for weight regulation. EXAMINATIONS: On physical examination, cachexia, bradycardia, lanugo hair on face and back, and cyanosis of hands and feet were observed. In the laboratory findings, leukopenia, recurrent low potassium and an elevated mean corpuscular volume (MCV) were remarkable. DIAGNOSIS, TREATMENT AND COURSE: We diagnosed anorexia nervosa, binge/purging type (AN-BP). We treated the patient for seven weeks in a multimodal setting specific for patients with eating disorders. She gained 3.9 kg (11% of her initial weight). Special challenges included the complications of her laxative abuse as well as her distinct body image disturbance. With knowledge of her background, we understood this misuse of hCG. CONCLUSION: Purging behaviour should be questioned in detail in patients with eating disorders, because purging methods are not always reported right away and are accompanied with great shame. However, purging behaviour can be very dangerous to one's health. Using a hCG diet (Hollywood diet) is a rare purging method in patients with anorexia nervosa.

[Hypothyroidism due to pseudo-malabsorption of levothyroxine--Case 12/2009]. / Hypothyreose infolge einer Pseudomalabsorption von L-Thyroxin--Fall 12/2009.

BACKGROUND: Hypothyroidism is a common endocrine disorder which is easily treatable by an appropriate thyroid hormone replacement therapy in the majority of patients. In some patients, hypothyroidism is refractory to oral levothyroxine substitution. Common causes of lack of response to levothyroxine replacement comprise non-compliance and impaired absorption. HISTORY: We report on a 32-year-old women who presented with persistent clinical and biochemical signs of hypothyroidism after thyroid surgery for Graves' disease despite high doses of levothyroxine replacement therapy. TREATMENT AND COURSE: An extensive evaluation for malabsorption syndromes proofed negative. Supervised absorption tests of two different levothyroxine preparations were normal. Pseudomalabsorption was presumed, though the patient continued to deny noncompliance. Supervised once weekly oral levothyroxine was advised. CONCLUSION: Non-compliance with medical therapy should be considered in patients with treatment-refractory hypothyroidism prior to initiation of an extensive evaluation for malabsorption syndromes. Supervised levothyroxine absorption test is a useful tool in the diagnostic workup for supposed pseudomalabsorption. In non-compliant patients, supervised once weekly levothyroxine replacement appears to be a safe and well-tolerated treatment option.

Pharmacogenetics of antimalarial drugs: effect on metabolism and transport.

The prevention and management of malaria is primarily based on the use of drugs. Clinical trials have however revealed that between individuals there is large variability in the pharmacokinetic profiles of many antimalarial drugs. The resulting variations in concentrations of the drug within plasma might lead to either suboptimum effectiveness or drug toxicity in some patients. The evidence is increasing that polymorphically expressed drug-metabolising enzymes, predominantly various cytochrome P450 isozymes but also drug transporters, might contribute to the variability in drug response (incomplete cure, relapse, or resistance) or toxicity experienced with antimalarial drugs. For example, there is a clear association between concentrations of proguanil within plasma and certain genetic polymorphisms of CYP2C19, and genetically established levels of CYP2C8 might have important clinical implications in the toxicity of amodiaquine. Variation in the expression of drug-metabolising enzymes and transport proteins affects the pharmacology of antimalarial drugs. Exploration of pharmacogenetics might help to optimise the use of antimalarial drugs.

The clinical implications of ageing for rational drug therapy.

INTRODUCTION: The proportion of the elderly is constantly increasing and by the year 2025 20% of the population will be above 65 years of age. With advanced age, subjects will develop multiple diseases and often need to take several drugs. DISCUSSION: This polypharmacy increases the risk for drug interactions and adverse effects. In addition, age-related physiological changes affect different biological systems and can contribute to alterations in pharmacokinetics and pharmacodynamics in older patients, which are more often seen in the frail than in the fit elderly. These features will complicate drug therapy in the elderly, and a careful dose titration is advisable. Furthermore, inappropriate drug prescription and non-adherence to medication represent common therapeutic challenges in elderly subjects. To date, there is no evidence of any effective antiageing agent. CONCLUSION: This review summarizes present knowledge of age-related problems in drug action and their clinical implications for an increasingly important population.

[Quality of antithrombotic therapy in patients with chronic atrial fibrillation: the AFib Trial]. / Qualität der antithrombotischen Therapie bei chronischem Vorhofflimmern: AFib-Studie.

BACKGROUND: Large randomised studies have definitely shown that oral anticoagulation effectively reduces thromboembolic complications, e.g. stroke, in patients with chronic non-valvular atrial fibrillation (AFib). However, less than 50% of the eligible AFib patients receive anticoagulation, although their risk of thromboembolic disease is increased 5-7 fold as compared to individuals who have a regular sinus rhythm. This is the reason why undertreatment needs to be evaluated and addressed. In Germany, data on the antithrombotic therapy of these patients are sparse, national guidelines are lacking. AIM OF THE STUDY: This prospective cohort study is the first one to evaluate the quality of antithrombotic prevention in two groups of AFib outpatients in two different, socio-demographically comparable regions of Germany (Südbaden and Südwürttemberg) over a period of several years. Quality of care is defined as the percentage of AFib patients in a certain region treated according to international guidelines. If the percentage in both cohorts does not exceed 80%, guidelines are to be developed and implemented in Südwürttemberg on consideration of the specific treatment conditions in this region; their applicability is to be evaluated later. METHODS: Office-based specialists of internal and general medicine are currently recruiting 200 AFib patients in each study region for documentation of their clinical data. Besides the quality of antithrombotic chemoprevention, relevant problems emerging in antithrombotic therapy in an ambulant setting will be identified. In the area of intervention (Südwürttemberg) experts and office-based physicians will exclusively develop evidence-based guidelines and disseminate them among doctors. Six months after the implementation of these guidelines in Südwürttemberg, their influence on prescribing patterns will be determined by comparing the proportion of anticoagulated AFib patients in Südwürttemberg to that of the control cohort (Südbaden). In addition, secondary outcomes of interest include deaths, days of hospitalisation, and incidence of stroke or bleeding episodes for different antithrombotic treatments.