Disease-Modifying anti-rheumatic drugs

(DMARDS)

Uses and MOA

v  slow down destruction of the collagen and bone so will slow down the progression of the disease

• Azathrionprine (Imuran)
• Cyclosporin
• Gold containing compounds
• Hydroxychloroquine (Plaquenil)
• Leflunomide (Arava)
• Methotrexate
• Penicillamine
• Sulfasalazine

LG      MASH    PC

Methotrexate

MOA and Uses

DMARD - "Anti-neoplastic" - commonly used first before any other DMARDS

• MOA: inhibit dihydrofolate reductase, leading to reduced DNA synthesis thus reduces lymphocyte activity and proliferation
• Given once per week

Methotrexate

ADR

• Hepatoxicitiy
• myelosuppression
• pulmonary toxicity
• teratongenic

"Tera    Myelo"

HP Toxicity

ADR are lessened by co-administration of Folic acid

*SHould monitor Albumin, LFTs, creatinine, CBC

Leflunomide (Arava)

Use and MOA

DMARD - "used in pts intolerant or non-responsive to MTX"

• MOA: inhibits an enzyme required for pyrimidine synthesis thus leads to reduced DNA synthesis and reduced lymphocyte proliferation
• This is a prodrug and requires a loading dose

Leflunomide (Arava)

ADR

• loss of body weight
• reversible increase in liver enzymes, can lead to fatal hepatoxicity
• teratogenic: child-bearing age must have negative pregnancy test and use contraceptives

"DMARD"

• MOA: when it is cleaved to 50aminosalicyclic acaid and sulfapyridine, the sulfapyridine may inhibit cytokine produciton
• ADR: photosensitivity, orange discoloration of skin and urine, neutropenia, and rash

OR PN

*Co-administer with folic acid to prevent anemia

"DMARD"

Less effective than other DMARDS thus only for mild RA

• MOA: may inhibit interleukin-1 release
• Maximal effect not seen for several months, D/C if no benefits after 6 months
• ADR: dose-dependent irreversible retinopahty leading to vision loss

"DMARD"

• MOA: UNK

• Oral gold: Auranofin
  • Low efficacy, poor GI tolerance
  • maximal effects not seen for 6 months
•  Injectible gold: Solganol
  • intramuscular
  • more effective than oral
•  ADR: dose- dependent
  • agranulocytosis
  • dermatitis (rash-aviod sun)
  • proteinuria

D R A P    A S

DMARD- also used as chelator in heavy metal toxicity

• MOA: UNK
• slow onset, must titrate dose upward q 3months

• ADR:
• agranulocytosis
• Lupus
• Myasthenia Gravis
• proteinuria
• skin lesion

P A L M     S A

"Reserved for severe RA or resistant to other drugs"

Azathioprine (Imuran)

• MOA: inhibits an enzyme required for purine syn
• ADR: hepatoxicity,  BMS : bone marrow suppression

Cyclosporin

• MOA: inhibits T cell activity
• ADR: HTN, renal dysfunction
• this drug has alot of D-D interaxn

                    D R   HTN

• Enbrel (etanercept)
• Humira (adalimumab)
• Kineret (anakinra)
• Orencia (abatacept)
• Remicade (infliximab)

HERO K

• These may be added to traditional DMARDS
• may replace traditional DMARDs if poor response, ADR intolerable, or response has faded
• rapid response seen in days
• after one year, their efficacy is equal to MTX
• very EXPENSIVE!!

"Biological DMARDs" 

MOA: Bind to CD80 and CD86 on antigen presenting cells and this prevents their interaction with Tcells. So net effect is reduced T cell activation

ADR: infections and malignancies

Biological DMARDs with anti-TNF activity

MOA and Regimens

"Tumore necrosis factor-alpha is a cytokine that is found in high concentration in synovial fluid of RA pts leading to bone and joint damage" 

• Enbrel : recombinant soluble TNF receptor
  • SQ twice a week
•  Remicade: monoclonal Ab against TNF
  • IV q 8 weeks
•  Humira: monoclonal Ab against TNF
  • SQ q 2 weeks

Biological DMARDs with Anti-TNF activity

ADR

• ADR:
  • itching and swelling at injeciton site
  • IV Remicade: fever and hypotension
  • severe infections: sepsis, TB
•  Avoid use in pts with or prone to infections
• aviod using live vaccines in pts taking this drug
• aviod in pts with HF
  • Remicade increases mortality in HF pts
•  DO NOT USE with Orencia

"Interleukin-1 is a cytokine that is foud in high conc in synovial fluid of RA pts leading to bone and joint damage"

Kineret: a recombinant IL-1 recceptor antag

• SQ INJ daily
• ADR:
  • itchiness at injection site
  • severe infections: pneumonia
•  has synergistic effects with anti-TNF drugs but do not combine due to inc risk of developing severe infection and neutropenia