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[Drug interactions in dermatological systemic treatment].

ABSTRACT: Severe pharmacological side effects have an occurrence of 5-7% and represent a frequent reason for hospital admission. The prevalence of undesired pharmacological side effects during hospitalization is even higher with approximately 11.5%. The causes are often interactions between drugs due to the polypharmacy of multimorbid older patients. On average, a 65-year-old male patient will simultaneously be taking 5 medications. Due to the increasing use of systemic drugs in dermatology and the simultaneously increasing polypharmacy, knowledge of interactions between medications is essential for dermatologists in order to avoid severe side effects of drugs. This article provides assistance in order to identify patients and medications with a high risk for severe interactions and, therefore, to avoid the occurrence of undesired effects or the reduction of the therapeutic effects of active substances. We would like to point out that this article deals with individual aspects and does not mean that the testing of individual drug interactions with interaction programs can be omitted. It should also not be neglected that in addition to prescription-only drugs, foodstuffs, dietary supplements and herbs can also lead to interactions with medications.

SUBMITTER: Krause K

PROVIDER: S-EPMC7803714 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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[Drug interactions in dermatological systemic treatment].

Krause Kristina K Jahn Katharina K Homey Bernhard B

Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 20210101 1

Severe pharmacological side effects have an occurrence of 5-7% and represent a frequent reason for hospital admission. The prevalence of undesired pharmacological side effects during hospitalization is even higher with approximately 11.5%. The causes are often interactions between drugs due to the polypharmacy of multimorbid older patients. On average, a 65-year-old male patient will simultaneously be taking 5 medications. Due to the increasing use of systemic drugs in dermatology and the simult ...[more]

PMID: 33242135

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Project description:Methotrexate (MTX) is widely used as disease modifying treatment for psoriasis and psoriatic arthritis (PsA). Rheumatological and dermatological guidelines to prevent MTX-induced adverse events diverge in the number and frequency of blood tests. These differences are not based on evidence indicating a higher risk for patients with psoriasis compared to PsA or rheumatic arthritis (RA). This raises the question if multiple testing increases safety, or results in false positive signals potentially leading to early withdrawal of an effective treatment.Compare the effects of MTX monitoring strategies by rheumatologists and dermatologists regarding drug survival, reasons for withdrawal and safety.Retrospective follow-up of all patients diagnosed with psoriasis by dermatologists or PsA by rheumatologists. Included were consecutive patients who started methotrexate (MTX) between 2006 and 2012 and had a scheduled follow-up by dermatologist or rheumatologist. Exclusions were: drug not started after the first prescription or incomplete availability of lab data. Data were extracted from electronic records: start and stop dates and dosing of MTX; treatment with folic acid and dose; reasons for withdrawal of MTX; numbers of blood sampling and types of laboratory tests performed for MTX safety; number of abnormal tests; occurrence of any serious adverse event (SAE).190 Psoriasis and 196 PsA patients starting methotrexate (MTX) were included. Age and sex were comparable. PsA patients used higher initial and maximum doses of MTX and folic acid, but psoriasis patients had a higher frequency of abnormal laboratory results (0.14 vs 0.03 per treatment month, p<0.001), resulting in a striking difference in withdrawal of MTX for abnormal liver enzymes (15.8% vs 3.6%, p<0.001). In PsA patients MTX was withdrawn less frequently for ineffectiveness (15.8 vs 24.2%, p<0.05) leading to longer drug survival in the first course of treatment (37.4±30 vs 18.8±19.1 months). Repeated courses of MTX were more often prescribed by rheumatologists than by dermatologists. There were no significant differences in the occurrence of SAE (psoriasis 0.0041 vs PsA 0.0038 per treatment month) or death (1.6% vs 2.0%) between these groups. Hospital admissions related to infection were recorded in 6 (3.1%) PsA vs 4 (2.1%) psoriasis patients.Strict monitoring by dermatologists resulted in more abnormal findings, which reduced drug survival of MTX. The limited monitoring strategy by rheumatologists was not associated with more SAEs. Further research in other populations is needed to confirm whether reduced intensity of monitoring can optimize the use of MTX with sufficient long-term safety.

Project description:Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and migration occurs, along with limited differentiation of oligodendrocytes and oligodendrocyte death. From one day to five days after injury, a shift in dendrimer co-localization occurred. Initially, dendrimer predominantly co-localized with astrocytes, with a subsequent shift towards microglia. Co-localization with oligodendrocytes reduced over the same time period, demonstrating a region-specific uptake based on the progression of the injury. We further show that systemic administration of a single dose of dendrimer-N-acetyl cysteine conjugate (D-NAC) at either sub-acute or delayed time points after injury results in sustained attenuation of the 'detrimental' pro-inflammatory response up to 9days after injury, while not impacting the 'favorable' anti-inflammatory response. The D-NAC therapy also led to improvement in myelination, suggesting reduced white matter injury. Demonstration of treatment efficacy at later time points in the postnatal period provides a greater understanding of how microglial activation and chronic inflammation can be targeted to treat neonatal brain injury. Importantly, it may also provide a longer therapeutic window.

Dataset Information

[Drug interactions in dermatological systemic treatment].

Publications

[Drug interactions in dermatological systemic treatment].

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