Combined use of an ACE-inhibitor and spironolactone in patients with heart insufficiency. / Risikoreiche Kombination oder leitliniengerechte Verordnung? ACE-Hemmer und Spironolacton: Bei Herzinsuffizienz indiziert.

A patient with cardiac insufficiency takes the ACE-Inhibitor Enalapril as well as Spironolactone regularly. In the interaction monographs of the German ABDA-database there is a note that combined use of these substances should be avoided due to an increased risk of hyperkalemia ­ is there a medication related problem? There is evidence from clinical studies, that combined use of ACE-inhibitors and potassium-sparing agents indeed increases the risk of severe hyperkalemia. The risk seems to be related to the dose of the potassium-sparing agent. However, in patients with cardiac insufficiency NYHA-class II-IV and an ejection fraction of ≤ 35%, the addition of spironolactone to an ACE-inhibitor and betablocking agent reduces mortality and hospitalization for cardiovascular problems. Therefore the combination is indicated in these patients. To minimize the risk for severe adverse events close monitoring of serum potassium and renal function is mandatory. Moreover, additional risk factors for hyperkalemia such as intake of potassium supplements or NSAID should be avoided.

[Medication reviews in community pharmacies: An approach to external quality assessment]. / Medikationsanalysen in öffentlichen Apotheken: Konzept zur externen Qualitätsüberprüfung.

BACKGROUND: A medication review aims at the optimization of medication use, the detection of drug-related problems (DRPs) and the recommendation of interventions. As part of the pilot project "Arzneimittelinitiative Sachsen-Thüringen" (ARMIN) and caused by the introduction of several training programs, numerous public pharmacies in Germany currently offer medication reviews for patients. However, a standardized method for external quality control has so far not been established. METHODS: A round robin test for medication reviews was designed in written form by five pharmacists with expertise in different areas (Drug information service ARMIN, Saxonian Chamber of pharmacists, public pharmacy, hospital pharmacy), based on the recommendations of the guideline for medication reviews of the German Federal Chamber of Pharmacists (Bundesapothekerkammer). On the basis of a fictitious case study the participants were asked to check a patient's medication data for the presence of DRPs, propose possible solutions and generate a medication plan. The solutions were assessed by two pharmacists of the drug information service ARMIN on the basis of a best practice solution that had been consented in the study group beforehand. RESULTS: 102 pharmacists and 13 pharmacy students in internship took part in the round robin test. On average, participants achieved a score of 7,62 out of 9 for recognizing DRPs and recommending solutions and a score of 0,79 out of 1 for generating a correct medication plan. 106 participants (92%) met the requirements for successful participation (recognizing the three most relevant DRPs and at least one further DRP as well as generating an adequate medication plan). The implementation of the approach described here proved to be practicable The State Directorate of Saxony accepted the round robin test as a measure for external quality assessment in accordance with legal requirements. CONCLUSIONS: Due to the nationwide introduction of medication reviews as a pharmaceutical service in June 2022, medication reviews performed by German community pharmacies will gain in importance in the coming years. This is why quality assurance is necessary. Since the participants' performance in medication analysis becomes comparable by completing the round robin test, this instrument appears to be potentially suitable for the external quality assessment of medications reviews nationwide.

Effects of the Light/Dark Phase and Constant Light on Spatial Working Memory and Spine Plasticity in the Mouse Hippocampus.

Circadian rhythms in behavior and physiology such as rest/activity and hormones are driven by an internal clock and persist in the absence of rhythmic environmental cues. However, the period and phase of the internal clock are entrained by the environmental light/dark cycle. Consequently, aberrant lighting conditions, which are increasing in modern society, have a strong impact on rhythmic body and brain functions. Mice were exposed to three different lighting conditions, 12 h light/12 h dark cycle (LD), constant darkness (DD), and constant light (LL), to study the effects of the light/dark cycle and aberrant lighting on the hippocampus, a critical structure for temporal and spatial memory formation and navigation. Locomotor activity and plasma corticosterone levels were analyzed as readouts for circadian rhythms. Spatial working memory via Y-maze, spine morphology of Golgi-Cox-stained hippocampi, and plasticity of excitatory synapses, measured by number and size of synaptopodin and GluR1-immunreactive clusters, were analyzed. Our results indicate that the light/dark cycle drives diurnal differences in synaptic plasticity in hippocampus. Moreover, spatial working memory, spine density, and size and number of synaptopodin and GluR1 clusters were reduced in LL, while corticosterone levels were increased. This indicates that acute constant light affects hippocampal function and synaptic plasticity.

Analysis of secondary care data to evaluate the clinical relevance of the drug-drug interaction between amlodipine and simvastatin.

BACKGROUND: Pharmacokinetic analyses revealed an increase in the bioavailability of simvastatin when co-administered with amlodipine [Nishio S et al. Hypertensin research 2005; Son H et al. Drug metabolism and pharmacokinetics 2014]. This may induce an increased risk of muscle toxicity for patients who receive this combination. So far, no in vivo data on the clinical relevance of this interaction exist. The objective of the present analysis was to determine the number of patients with concomitant treatment of amlodipine and simvastatin. Subsequently, the data was analyzed for the indication of muscular discomfort. Patients with combined prescription of amlodipine and another hydroxymethylglutaryl-CoA-reductase inhibitor except simvastatin or patients receiving simvastatin without amlodipine served as control groups. METHODS: The present analysis used secondary data from the health insurance company AOK PLUS including information regarding diagnosis and drug prescriptions. RESULTS: In total, 67.081 patients corresponding to 4.93% of the analyzed collective received a combined prescription of amlodipine and simvastatin. The absolute frequency increased continuously over time. Muscular discomfort was detected in a) 6.20% of the patients receiving amlodipine and simvastatin, b) 6.60% of the patients receiving amlodipine and another hydroxymethylglutaryl-CoA- reductase inhibitor and c) 8.04% of the patients with simvastatin only. CONCLUSIONS: The present analysis shows an increasing trend of combined prescriptions of amlodipine and simvastatin. Evidence for simvastatin dose adaptation or therapy switch to another hydroxymethylglutaryl-CoA-reductase inhibitor, however, was not found. Muscular discomfort does not occur more often in patients with amlodipine and simvastatin compared to the two control groups. The results of the present analysis reveal no evidence for a clinically relevant interaction between amlodipine and simvastatin.

[Medication management: Simvastatin and Amlodipin - a clinically relevant drug-interaction?] / Medikationsmanagement: Simvastatin und Amlodipin: Eine klinisch relevante Wechselwirkung?

The clinical relevance of the drug-drug interaction simvastatin and amlodipine is appraised controversially by german simvastatin Summary of Product Characteristics (SPCs) and different drug interaction databases. Results of clinical trials have shown that simultaneous administration of simvastatin and amlodipine can increase simvastatin bioavailability. However, it is unclear whether this increase is associated with a higher risk for adverse drug events. So far there is no evidence that the combination might increase cases of myopathy or rhabdomyolysis. Therefore combined treatment with amlodipine and up to 40 mg simvastatin daily seems clinically justifiable if the patient does not report adverse events. If myopathy or muscle weakness occur, simvastatin dose should be reduced to 20 mg daily or the patient should be switched to pravastatin, fluvastatin or rosuvastatin. The highest approved dose of simvastatin (80 mg) is generally not recommended in new patients because of increased risk of muscle damage.