Pharmacology of inhibitors of Janus kinases – Part 2: Pharmacodynamics
Summary As small molecules, the Janus kinase inhibitors have different, dose‐dependent pharmacological binding selectivities, which, however, do not allow reliable statements about the clinical specificity of desired or side effects. It is therefore of particular importance to recognize that the pha...
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| Published in: | Journal der Deutschen Dermatologischen Gesellschaft Vol. 20; no. 12; pp. 1621 - 1631 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Germany
Wiley Subscription Services, Inc
01-12-2022
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Summary
As small molecules, the Janus kinase inhibitors have different, dose‐dependent pharmacological binding selectivities, which, however, do not allow reliable statements about the clinical specificity of desired or side effects. It is therefore of particular importance to recognize that the pharmacodynamics of the individual Janus kinase inhibitors as a function of the treated indication is essentially determined by variable levels of regulation of the JAK/STAT signaling pathway and the pharmacokinetic conditions. Against this background, it becomes clear that only clinical trial data in defined indications are suitable for evaluating the efficacy and safety of Janus kinase inhibitors. An uncritical extrapolation of observations regarding efficacy and safety from studies of other indications should therefore only be made with due caution. |
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| Bibliography: | JAK inhibitors are contraindicated during pregnancy and lactation. The re‐synthesis time of JAK isoforms is approximately 2–4 hours. Evidence‐based counseling of patients on potential adverse effects is only possible on an individual basis with reference to treatment indication, substance used, dosage, and patient‐specific factors. JAK inhibitors of the alpha group have a purine‐like backbone. Before and during therapy, the function of the relevant organs of elimination should be monitored by laboratory chemistry. The structure of beta‐group JAK inhibitors was specifically synthesized by “chemical modeling” to optimize binding. Active viral hepatitis, HIV infection, and latent or active tuberculosis should be excluded prior to initiation of therapy. Patterns of effects and side effects of JAK inhibitors are substance ‐specific and should not be evaluated as group effects. Inhibition of JAKs increases the risk of infections or the reactivation of persistent infections (especially herpes zoster). The relevance of an increased risk of thromboembolic events can only be assessed individually with reference to treatment indication, age, sex, JAK inhibitor, dosage and anamnesis. An increased risk of malignancy cannot be excluded with certainty for any JAK inhibitor at present. JAK inhibitors have a different structure‐effect relationship. The JAK inhibitors represent a chemically inhomogeneous group of drugs with different pharmacodynamic patterns of action and side effects. Section Editor Prof. Dr. Trautinger, St. Pölten Due to the pharmacodynamics of JAK inhibitors, dose‐dependent undesirable effects can occur. Except for baricitinib and delgocitinib, coapplied agents that are eliminated via the cytochrome P450 complex or affect its activity should be considered. Data on pharmacological binding selectivity are not indicative of clinical specificity of effects. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1610-0379 1610-0387 |
| DOI: | 10.1111/ddg.14885 |