General Pharmacology

DMARDs Pharmacology!

Nov 22nd, 2020
dmards pharmacology

DMARDs Pharmacology

DMARDs are disease-modifying anti-rheumatic drugs used to treat autoimmune conditions such as rheumatoid arthritis. Here, we review DMARDs pharmacology – the primary members, how they work, and what other, more specific indications they are used to treat.

Even though DMARDs share a common indication – rheumatoid arthritis – individual DMARDs are used to treat a variety of other inflammatory and auto-immune diseases.

The purpose of DMARDs is to slow the progression of rheumatoid arthritis. In contrast, NSAIDs (non-steroidal anti-inflammatory drugs) are used to treat symptoms of these conditions – such as inflammation – but do not seek to address any underlying cause.

DMARDs are used to address these cause and therefore slow disease progression. DMARDs also differ from steroid drugs. Whereas steroids dampen the immune response, DMARDs address the underlying cause.

Before we learn more about how to choose the right DMARD and how specific drugs achieve their therapeutic effects, let’s first learn about DMARDs classification and what indications they are used to treat.

DMARDs Classification

DMARDs are classified as:

  • Synthetic DMARDs (sDMARD)
  • Conventional synthetic (csDMARD): hydroxychloroquine, methotrexate; the traditional examples of DMARDs.
  • Targeted synthetic (tsDMARD): drugs developed with the purpose of targeting a specific molecular structure.
  • Biological DMARDs: modern drugs developed through genetic engineering.

Synthetic DMARDs are traditional, small molecular mass drugs in contrast to the heavier molecular mass biologic agents.

Due to their mechanism of action, DMARDs are effective in the treatment of other inflammatory-autoimmune states. Examples include:

  • Crohn’s disease
  • Ankylosing spondylitis
  • Psoriatic arthritis
  • Systemic lupus erythematosus (SLE)
  • Sarcoidosis
  • Immune thrombocytopenic purpura (ITP)
  • Sjögren syndrome

The function of DMARDs is to:

  • Reduce pain and inflammation
  • Prevent long-term joint damage
  • Preserve the structure and function of bone/joints

However, treating autoimmune conditions such as these can take many weeks/months to take effect. The precise time depends on the drug, the patient, their condition or any underlying conditions, and disease progression to date.

Typical treatment regimens include:

  • Methotrexate: 6-8 weeks
  • Hydroxychloroquine: 2-4 months
  • Leflunomide: 4-8 weeks
  • Sulfasalazine: 6 weeks to 3 months
  • Abatacept: 3 months
  • Rituximab: 3 months
  • Tocilizumab: 4-8 weeks

DMARDs are not administered to provide immediate symptomatic relief. Other drugs, such as NSAIDs or analgesics, are instead given for this purpose. For this reason, DMARDs are sometimes referred to as “remission inducing drugs”.

Choosing the Right DMARD

When choosing a DMARD, there are a variety of factors to consider.

  • First, the autoimmune/inflammatory state and its severity. These same factors also influence what dosage regimen may be adopted, and what monitoring program the patient can expect to undertake.
  • Second, patient preference. Patients may have responded favorably to some DMARD over another. Side effect profiles must be considered, too. Patients should understand the likely side effects of each drug and how it may impact their day-to-day life.
  • Third, likely clinical benefits. The ratio of clinical benefit versus adverse effect profile must be considered. Patients should be informed of expected results and the capacity to which the drug can improve their lives.
  • Fourth, elimination of risk factors. Patients may be tested for past exposure to specific infections. These blood tests are a necessary component that may rule out what DMARD may be prescribed to the patient.
  • Fifth, patient response. One DMARD may prove effective, whilst another proves to be somewhat ineffective or whose side effects have become too burdensome. In some cases, more than one DMARD is needed. Often, it comes down to trial and error to determine the optimum DMARD(s) to treat the specific needs of the patient.

These are not the only clinical factors to consider, but they place into focus how and why one DMARD may be chosen over another.

Pharmacology of DMARDs

Here, you can learn more about how specific DMARDs achieve their therapeutic effects. The mechanism of action of DMARDs varies considerably, as tabled here:

DMARD Mechanism of Action
Methotrexate Purine metabolism inhibitor
Hydroxychloroquine Induces apoptosis of inflammatory cells; decreases chemotaxis; targets TNF-alpha
Leflunomide Pyrimidine synthesis inhibitor via inhibition of the enzyme dihydroorotate dehydrogenase
Cyclosporine Calcineurin inhibitor
Chloroquine Suppression of IL-1; apoptosis of inflammatory cells
Azathioprine Purine synthesis inhibitor
Infliximab TNF inhibitor
Anakinra Antagonist of IL-1
Adalimumab TNF inhibitor
Abatacept Binds to CD80 and CD86, preventing T-cell activation
Golimumab TNF inhibitor
Rituximab Acts against CD20 protein on B-cell surface, triggering cell death
Sulfasalazine Suppression of IL-1 and TNF-alpha
Tocilizumab IL-6 receptor antagonist
Tofacitinib Inhibitor of the kinases JAK1 and JAK3, which transmit extracellular data to the cell nucleus – influencing DNA transcription
Certolizumab pegol TNF inhibitor

That concludes our review of DMARDs pharmacology. Check back to our pharmacy blog soon for more exclusive content to help you master the science behind drugs and medicines.