The Rheumatologist
COVID-19 NewsACR Convergence
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Axial Spondyloarthritis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Interprofessional Perspective
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Gout Resource Center
      • Axial Spondyloarthritis Resource Center
      • Psoriatic Arthritis
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Chronotherapy with Glucorticoids in Rheumatoid Arthritis

Chronotherapy with Glucorticoids in Rheumatoid Arthritis

January 17, 2011 • By Frank Buttgereit, MD

  • Tweet
  • Email
Print-Friendly Version / Save PDF

In 1950, Philip S. Hench and his co-workers Edward Kendall and Tadeus Reichstein received the Nobel Prize for medicine for their landmark discovery of glucocorticoids and the beneficial effects in rheumatoid arthritis (RA). Since that time, glucocorticoids have become one of the most commonly prescribed classes of drugs in all of medicine, although many issues about optimal use remain surprisingly unknown. This article summarizes the current knowledge on the mode of action of glucocorticoids and highlights approaches to improve the risk–benefit ratio of these important drugs, as well as the development of novel glucocorticoids or glucocorticoid receptor ligands. In this regard, the focus of this discussion will be on a new concept in drug administration termed chronotherapy with modified-release (MR) prednisone for the treatment of RA.

You Might Also Like
  • Glucocorticoid Use for Rheumatoid Arthritis Still Sparks Debate
  • Glucocorticoid Use in Rheumatoid Arthritis Management Focus of Ongoing Debate
  • Prednisone Might be the Missing Ingredient in the American College of Rheumatology’s Recommendations for Treating Patients with Rheumatoid Arthritis
Explore This Issue
January 2011

Glucocorticoids’ Mode of Action

As shown in extensive studies in vivo and in vitro, glucocorticoids mediate their antiinflammatory and immunosuppressive effects by four different mechanisms that, unfortunately, also produce their serious adverse effects. These mechanisms include:

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE
  1. The classical genomic mechanism resulting from activation of the cytosolic glucocorticoid receptor (cGCR);
  2. Secondary nongenomic effects initiated by the cGCR;
  3. Membrane-bound glucocorticoid receptor (mGCR)– mediated nongenomic effects; and
  4. Nonspecific, nongenomic effects caused by interactions with cellular membranes.1-3
Arthritis specialists (left to right) Dr. C. H. Slocumb, Dr. Edward C. Kendall, Dr. Philip S. Hench, and Dr. H. F. Polley examining a patient at the Mayo Clinic.
Arthritis specialists (left to right) Dr. C. H. Slocumb, Dr. Edward C. Kendall, Dr. Philip S. Hench, and Dr. H. F. Polley examining a patient at the Mayo Clinic.

Each of these mechanisms will be considered in turn.

Glucocorticoid Mechanisms of Action

Classical genomic mechanism: The term classical genomic refers to the most important mechanism of glucocorticoid action that results in changes in gene expression via transactivation and transrepression. This mechanism involves passage of glucocorticoid molecules through the plasma membrane, high-affinity binding of these molecules to the inactive cGCR, formation of the activated glucocorticoid/cGCR complex, and translocation of the complex into the nucleus. The term transactivation refers to transcriptional transactivation by binding of a dimerized glucocorticoid receptor (GR) protein complex to the promoter of glucocorticoid-regulated genes, ultimately leading to upregulated synthesis of certain regulatory proteins. The interference with the activity of (proinflammatory) transcription factors (such AP1, NF-қB, or IRF-3) by GR monomers is called transrepression and leads to the down-regulation of (proinflammatory) protein synthesis. It should be stressed that these processes require time to occur—30 minutes or more pass before significant changes are recognized in regulator protein concentrations. It usually takes hours or days before changes on a cell, tissue, or organ level become evident. In contrast, nongenomic effects occur rapidly, within seconds or minutes.

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

Pages: 1 2 3 4 5 6 7 | Single Page

Filed Under: Conditions, Rheumatoid Arthritis Tagged With: Drugs, glucocorticoid, Pathogenesis, Research, Rheumatoid arthritis, TreatmentIssue: January 2011

You Might Also Like:
  • Glucocorticoid Use for Rheumatoid Arthritis Still Sparks Debate
  • Glucocorticoid Use in Rheumatoid Arthritis Management Focus of Ongoing Debate
  • Prednisone Might be the Missing Ingredient in the American College of Rheumatology’s Recommendations for Treating Patients with Rheumatoid Arthritis
  • New Research into Rheumatoid Arthritis, Gout Includes Updates on Methotrexate, Biologics, Ultrasound

Meeting Abstracts

Browse and search abstracts from the ACR Convergence and ACR/ARP Annual Meetings going back to 2012.

Visit the Abstracts site »

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

Simple Tasks

Learn more about the ACR’s public awareness campaign and how you can get involved. Help increase visibility of rheumatic diseases and decrease the number of people left untreated.

Visit the Simple Tasks site »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use / Cookie Preferences

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2023 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)