Presentation on Present status of DMARDS in the treatment of RA

Objective

• To highlight the present status of disease modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis

Introduction

• DMARDs (disease modifying antirheumatic drugs) are drugs which can suppress the rheumatoid process and bring about a remission, but do not have nonspecific anti-inflammatory or analgesic action.

Classification of Anti-rheumatic drugs

A. DMARDs:

• Immunosuppressants: Methotrexate, Cyclosporine, Azathioprine
• Sulfasalazine
• Chloroquine or hydroxychloroquine
• Leflunomide
• Gold salts
• d-Penicillamine

B. Biological response modifiers(BRMs):

• TNF-α inhibitors: Etanercept, Infliximab
• IL-1 antagonist: Anakinra

C. Adjuvant drugs

• Corticosteroids: Prednisolone

Immunosuppressants

Methotrexate:

• First choice and standard drug for rheumatoid arthritis.
• Acts by inhibiting an enzyme dihydrofolate reductase
• Also inhibits other enzyme involve in protein synthesis as well as anti-inflammatory and cytokines modulating effect.
• Initially low dose(7.5-15 mg/week)
• Best tolerated among other DMARDs

Adverse drug effects

1. Nausea and mouth ulcer
2. Pancytopenia (low blood cells)
3. Liver cirrhosis
4. Acute pneumonitis

Contraindications
• Pregnancy
• Lactating mother
• Liver disease
• Leucopenia
• Peptic ulcer

Sulfasalazine

• It is a compound of sulfapyridine and 5-amino salicyclic acid (5-ASA)
• Useful in both RA and ulcerative colitis
• Much more safer than gold salts
• Second line drugs for milder cases
• Mode of action is unknown

Adverse drug effects:

1. Neutropenia, hemolytic anemia
2. Thrombocytopenia

Gold Salts

• Water soluble gold preparation like sodium aurothiomalate
• Gets deposited in the synovial macrophages in actively inflammed joints and inhibits their function.

Adverse drug effects:

• Dermatitis, nephropathy, bone marrow depression and liver damage.

Etanercept

• It is a recombinant fusion protein of TNF-receptor and Fc portion of human IgG
• Reserved for the patients who have failed to respond to adequate trials of atleast two DMARDs

Adverse drug reaction:

1. Pain, redness, itching, swelling at the infection site
2. Chest infection may be increasedd-Penicillamine
3. Splits the rheumatoid factor and also selectively reduces the serum levels of calcium immunoglobin
4. Adverse drug reactions incidences are high so not commonly used

Gold salts and d-penicillamine should not be combined for the treatment of RA (because of severe ADRs). Gold salts and d-penicillamine are not used in the present context because of severe adverse reactions i.e.

• Bone marrow depression
• Kidney and liver damage
• Ulceration

Presented by Students of KistMCTH 1st year students

1. Hemu Chaurasia(Roll no-36)
2. Jemesh Singh Maharjan (Roll no-37)
3. Jeni Thapa(Roll no-38)
4. Keshav KC (Roll no-39)
5. Manisha Bohara (Roll no-40)
6. Manisha Dhakal (Roll no-41)
7. Manisha Maharjan (Roll no-42)

Reference

1. Text book of Pharmacology- K D Tripathi
2. Text book of Pharmacology- Bennett and Brown