Despite the fact that biological treatments are very promising, classical immunosuppressants, antimalarial drugs and glucocorticosteroids are still very important and widely used in practice. Although drug interactions can have fatal consequences, few studies have reviewed drug interactions of these classical drugs used in rheumatology, and very few guidelines are available on this subject. Therefore, this report summarizes important interactions of immunosuppressants, antimalarial drugs and glucocorticosteroids with drugs commonly used in internal medicine. In the present study, more than 300 interactions were retrieved from the Micromedex ® database. The selection was reduced to the interactions rated as moderate, major or contraindicated. The selected interactions were further checked against PubMed ®, MEDLINE ®, InfoPharm Compendium of Drug Interactions and Summaries of Product Characteristics. For each interaction, its nature, mechanism, onset and clinical severity were indicated, documentation quality was rated and recommendations for clinical practice were formulated. Twenty significant interactions that we rated as moderate, severe and very severe were identified. Interacting drugs were warfarin, fluoroquinolones, azole antifungals, co-trimoxazole, proton pump inhibitors, amiodarone, cholestyramine, activated carbon, allopurinol, angiotensin-converting enzyme inhibitors, statins, digoxin, iron, aluminium and magnesium salts, and hepatotoxic and nephrotoxic agents.

• MeSH
• antimalarika škodlivé účinky   terapeutické užití   MeSH
• glukokortikoidy škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• lékové interakce MeSH
• lidé MeSH
• revmatické nemoci farmakoterapie   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antimalarika MeSH
• glukokortikoidy MeSH
• imunosupresiva MeSH

Results are presented on the effect of immunosuppressive substances such as chlorambucil, cyclophosphamide, azathioprine, amethopterine and a cortizone derivate of betamethasone, on the development of Fasciola hepatica in the rat. The suppression of the immune response of the host to immunosuppressants was reflected in an earlier start of migration of the flukes to the common bile duct, and in an earlier onset of egg production as compared with that in the controls. Of the substances employed, cyclophosphamide and betamethasone were the most effective ones within the period from week 2--6 p.i., which is the time during which the migration of the flukes in the liver parenchyma is highest. Pathological changes in the liver of the animals were less marked than those of the infected controls. Evidence was obtained on an increased pathogenicity of infective larval flukes causing a higher mortality of the hosts in comparison with that of the control animals. On the other hand, the administration of immunosuppressants did neither influence the total number of developed flukes nor the appearance of eosinophilia in the peripheral blood of the treated animals.

• MeSH
• betamethason farmakologie   MeSH
• cyklofosfamid farmakologie   MeSH
• fasciolóza imunologie   parazitologie   MeSH
• imunosupresiva farmakologie   MeSH
• játra parazitologie   MeSH
• krysa rodu Rattus MeSH
• methotrexát farmakologie   MeSH
• žlučové cesty parazitologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• betamethason MeSH
• cyklofosfamid MeSH
• imunosupresiva MeSH
• methotrexát MeSH

BACKGROUND: The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations. OBJECTIVE: To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022. METHODS: Treatment outcomes were compared using inverse probability of treatment weighting (IPTW) Cox regression. Outcomes were annualized relapse rates (ARRs), time to discontinuation, time to first relapse (TTFR) and time to 24-week confirmed disability progression (CDP) or 24-week confirmed disability improvement (CDI; in patients with baseline Expanded Disability Status Scale [EDSS] score ≥2). RESULTS: After IPTW, ARR was similar for DMF (0.13) and NSIS (0.16; p = 0.29). There was no difference in TTFR between cohorts (hazard ratio [HR]: 0.98; p = 0.84). The DMF cohort experienced longer times to discontinuation (HR: 0.75; p = 0.001) and CDP (HR: 0.53; p = 0.001), and shorter time to CDI (HR: 1.99; p < 0.008), versus the NSIS cohort. CONCLUSION: This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS.

• Klíčová slova
• Dimethyl fumarate, effectiveness, non-specific immunosuppressants, real-world, relapsing-remitting multiple sclerosis,
• Publikační typ
• časopisecké články MeSH

PURPOSE: The main aim was to evaluate the changes in beliefs about immunosuppressants over a 3-year period in patients after kidney transplantation. The second aim was to investigate the relationship between beliefs, medication adherence, and selected clinical outcomes such as graft functioning. PATIENTS AND METHODS: This observational follow-up study was conducted in the outpatient post-transplant clinic at the University Hospital Hradec Kralove in the Czech Republic. Adult patients, at least 4 weeks after kidney transplantation, were invited for the structured interview, which was followed by a self-administered questionnaire survey during their regularly scheduled visits at the clinic. Appropriate paired tests were used to compare two measurements of beliefs about immunosuppressants by BMQ-CZ© in 2016 (baseline) and in 2019 (follow-up). Self-reported adherence was measured by two validated tools (MARS-CZ© and BAASIS©) capturing implementation and discontinuation phases. A generalized linear model was used to investigate the relation between beliefs and the consecutive estimated glomerular filtration rate. RESULTS: The study involved 134 patients. Over time, their perceived treatment necessity beliefs of immunosuppressants decreased, while their treatment-related concerns increased. Overall self-reported non-adherence (ie, taking, dosing and discontinuation of immunosuppressants) was reported by 12% of the patients in both observation periods. In the follow-up period, timing non-adherence was reported by 52 (38.8%) patients. Higher baseline treatment concerns were associated with poor adherence whereas higher baseline treatment necessity beliefs corresponded with better kidney functioning, even after adjusting for age. CONCLUSION: Higher treatment necessity beliefs corresponded with better kidney functioning, whereas higher treatment concerns were related to non-adherence to immunosuppressants at the beginning of the observed period. Still, most patients accepted their medicines that do not come without risk. Nevertheless, decreasing treatment necessity beliefs on one hand, and increasing treatment concerns on the other, should be considered in clinical practice.

• Klíčová slova
• immunosuppressants, kidney transplantation, medication adherence, treatment concerns, treatment necessity beliefs,
• Publikační typ
• časopisecké články MeSH

• MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• pooperační péče * MeSH
• transferin analýza   MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH
• transferin MeSH

The aim of our study was to evaluate the efficacy of FK506, mycophenolate mofetil (MM) and aminoguanidine (AMG) on infiltration of macrophages (MPHs), neutrophils (NPHs) and dendritic cells (DC) into corneal grafts during the early phases after transplantation (Tx). Tx was performed in mice (C57BL/10 to BALB/c). Therapy included FK506 (0.2 mg/kg), MM (30 mg/kg) or AMG (0.1 g/kg), started at the day of Tx and was injected i.p. daily. Corneas were excised on the third and seventh day after Tx. Immunohistological evaluation using antibodies against MPHs, NPHs and DC was performed and corneal grafts were assessed in the periphery and in central part of the cornea separately. On the third day after Tx, a massive infiltration of MPHs and NPHs into corneal grafts was revealed; the DC infiltration was lower in all treated groups. Treatment with FK506 and MM led to a significant reduction of NPHs in the centers of the grafts, but not of MPHs. In contrast, AMG significantly reduced MPHs migration into allografts on the third day after Tx, whereas NPHs infiltration has not been attenuated. However, immunosuppressants had no influence on the infiltration of DC during early phases after Tx.

• MeSH
• časové faktory MeSH
• dendritické buňky účinky léků   MeSH
• guanidiny farmakologie   terapeutické užití   MeSH
• imunosupresiva farmakologie   terapeutické užití   MeSH
• infiltrace neutrofily účinky léků   MeSH
• kyselina mykofenolová analogy a deriváty   farmakologie   terapeutické užití   MeSH
• makrofágy účinky léků   MeSH
• modely u zvířat MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neutrofily účinky léků   MeSH
• počet buněk MeSH
• rejekce štěpu imunologie   prevence a kontrola   MeSH
• rohovka účinky léků   imunologie   chirurgie   MeSH
• takrolimus farmakologie   terapeutické užití   MeSH
• transplantace rohovky * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• guanidiny MeSH
• imunosupresiva MeSH
• kyselina mykofenolová MeSH
• pimagedine MeSH Prohlížeč
• takrolimus MeSH

Several candidate genes have been proposed as potential biomarkers for altered pharmacodynamics or pharmacokinetics of immunosuppressive drugs. However, there is usually only limited clinical evidence substantiating the implementation of biomarkers into clinical practice. Testing for thiopurine-S-methyltransferase polymorphisms has been put into routine clinical use quite widely, while the other pharmacogenetic tests are much less frequently used. Relatively good evidence appeared for tacrolimus-related biomarkers; thus, their utilization may be envisaged in the near future. Although the biomarkers related to mycophenolate, sirolimus or other drugs in the therapeutic class may be promising, further research is necessary to provide more robust evidence. The present review focuses on immunosuppressive drugs, excluding biological treatment.

• Klíčová slova
• donor, immunosuppressants, pharmacodynamics, pharmacogenomics, pharmacokinetics, recipient,
• MeSH
• farmakogenetika metody   MeSH
• genetické markery * MeSH
• imunosupresiva farmakokinetika   farmakologie   MeSH
• lidé MeSH
• methyltransferasy genetika   MeSH
• polymorfismus genetický MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• genetické markery * MeSH
• imunosupresiva MeSH
• methyltransferasy MeSH
• thiopurine methyltransferase MeSH Prohlížeč

Changes in the immune system induced by exogenous or endogenous factors may be accompanied with modifications of the activity of the drug metabolising enzymes in the liver. Some immunostimulatory agents are known to suppress the oxidative metabolism mediated by cytochromes P450. Possible effects of substances which suppress the immune responses of the organism have not been fully understood yet. The present study was undertaken to investigate the influence of immunosuppressants cyclophosphamide and dexamethasone on the CYP2D 1-dependent metabolism of dextromethorphan (DEM) in the isolated perfused liver from male rat donors (Wistar albino, 250-310 g). Recirculatory perfusion system was used with Williams' medium E (Sigma Chemicals Co.) as a perfusion medium (120 mL). DEM was administered as a 1 mg bolus into the perfusion solution at the start of each experiment after 20 min preperfusion. Samples of perfusate for HPLC determination of DEM and its O-demethylated metabolite dextrorphan (DOR) were taken at 15 min intervals for 120 min. The results have shown a rapid conversion of DEM to DOR in the isolated rat liver preparations. Pharmacokinetic parameters in the livers from intact rats were as follows: t1/2 DEM = 19.1+/-4.10 min, k(m) = 0.035+/-0.008 min(-1), Cl(m) = 4.21+/-0.97 mL x min(-1), AUC(DOR) = 2160+/-201 microg x min x L(-1). Pretreatment of rats with dexamethasone (4 mg/kg/day, iv, x 3 days) led to a significant increase in the concentration of dextrorphan in the recirculating solution, but it did not substantially change the kinetic constants of DOR formation (km = 0.036+/-0.004 min(-1), Cl(m) = 4.27+/-0.43 mL x min(-1)). Cyclophosphamide (100 mg/kg, ip, 1 dose on day 5 before perfusion) induced nearly twofold increase in the DOR concentrations in perfusate and thus highly significant (p < 0.01) changes of the kinetic parameters characterizing the increased rate of conversion of DEM to DOR (t1/2 DEM = 12.1+/-0.90 min, km = 0.055+/-0.004 min(-1), Cl(m) = 7.09+/-1.37 mL x min(-1), AUC(DOR) = 3602+/-154 microg x min x L(-1)). Considering that both cyclophosphamide and dexamethasone belong to the most widely used immunosuppressive drugs, their potential to promote the CYP2D-mediated metabolism might have a clinical impact in combined therapy of autoimmune or other diseases.

• MeSH
• alkoholoxidoreduktasy MeSH
• aromatické hydroxylasy * MeSH
• cyklofosfamid farmakologie   MeSH
• dexamethason farmakologie   MeSH
• dextromethorfan metabolismus   MeSH
• dextrorfan metabolismus   MeSH
• imunosupresiva farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• kinetika MeSH
• krysa rodu Rattus MeSH
• metylace MeSH
• potkani Wistar MeSH
• rodina 2 cytochromů P450 MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkoholoxidoreduktasy MeSH
• aromatické hydroxylasy * MeSH
• cyklofosfamid MeSH
• Cyp2d1 protein, rat MeSH Prohlížeč
• dexamethason MeSH
• dextromethorfan MeSH
• dextrorfan MeSH
• imunosupresiva MeSH
• rodina 2 cytochromů P450 MeSH
• systém (enzymů) cytochromů P-450 MeSH

• MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH

Immunosuppressive agents represent a class of drugs that inhibits activity of the immune system. They are mostly used in autoimmune diseases and other inflammatory conditions treatment and in prevention of recipient´s immune response to donors antigens in transplantations. There is a broad spectrum of different immunosuppressive drugs with various mechanisms of action. This article provides an overview of drugs currently registered as immunosuppressive agents in the Czech Republic and provides some insights what we might expect regarding this group of drugs in the future.

• Klíčová slova
• biologic treatment, fusion proteins, immunosuppression, kinase inhibitors, monoclonal antibodies, tolerance,
• MeSH
• autoimunitní nemoci * farmakoterapie   MeSH
• imunitní systém MeSH
• imunosupresiva * terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• imunosupresiva * MeSH