Antirheumatics

Question 0

DMARDs (Disease Modifying AntiRheumatic Drugs)

Answer 0

Can reduce joint inflammation, reduce or prevent joint damage, and maintain joint function and integrity
Should be employed early in treatment
Are slow acting drugs- effects may take weeks to months

Question 1

Initial treatment of rheumatoid arthritis

Answer 1

Start on DMARDs & use NSAIDs w/ or w/o corticosteroid to control symptoms
Once effective DMARD regimen is established the use of NSAIDs and corticosteroids can be minimized
Inadequate response to single agents combination therapies are often effective especially methotrexate & TNF inhibitor

Question 2

Traditional DMARDs

Answer 2

Methotrexate
Sulfasalazine
Have immunosuppressive and anti inflammatory effects

Question 3

Biological DMARDs

Answer 3

Adalimumab
Anakinra
Etanercept
Infliximab
Target proinflammatory cytokines which seem to be key inflammatory mediators in rheumatoid arthritis

Question 4

COX inhibitors & steroids used for rheumatoid arthritis

Answer 4

Aspirin
Celecoxib
Ibuprofen
Naproxen
Prednisone

Question 5

Methotrexate

Answer 5

DMARD of choice for rheumatoid arthritis
Induces an increase in adenosine release from injured cells
Adenosine acts on cell surface receptors to inhibit production of inflammatory cytokines (TNF-alpha, IFN-gamma) and other cellular functions

Question 6

Methotrexate adverse effects

Answer 6

GI mucositis, vomiting, diarrhea
Thrombocytopenia
Nephrotoxicity 
Long term use as in treatment for rheumatoid arthritis is assoc. with development of hepatotoxicity and pneumonitis
Teratogenic

Adverse effects can be prevented or managed with leucovorin or folic acid (cheaper & maybe better choice)

Question 7

Methotrexate contraindications

Answer 7

Pregnancy
Renal disease (drug is excreted in urine)
Lung disease (can cause pneumonitis)
Chronic liver disease (can cause hepatotoxicity)

Question 8

Sulfasalazine

Answer 8

Safer DMARD than Methotrexate for milder cases of rheumatoid arthritis 
Prodrug- converted by colonic bacteria to sulfapyridine (sulfonamide antibiotic) and 5-aminosalicylic acid (mesalamine, an antiinflammatory drug)- complete mechanism not clear
The drug (probably 5-aminosalicylic acid) increases adenosine levels, decreases IL-1 and TNF-alpha release, and inhibits NF-kappaB

Question 9

Sulfasalazine adverse effects

Answer 9

Nausea, vomiting, abdominal pain, diarrhea, anorexia

Hypersensitivity to drug is manifested as fever, exfoliative dermatitis, others

Question 10

Sulfasalazine contraindications

Answer 10

Allergy to sulfa drugs

Question 11

TNF-alpha inhibitors

Answer 11

Adalimumab
Infliximab
Etanercept
Appear more effective than Methotrexate & other DMARDs in halting joint destruction and are being used as first line therapy even though long term safety is unclear

Question 12

TNF-alpha inhibitor adverse effects

Answer 12

Increased risk of infection- latent tuberculosis can become activated (tuberculin skin testing recommended before treatment starts)
Injection reactions:
Etanercept & Adalimumab are injected subcutaneously & can cause erythema, pain, and pruritus at site
Infliximab is administered intravenously & can cause an infusion reaction manifested as fever & chills

Question 13

TNF-alpha contraindications

Answer 13

Active infections, history of recurring infections or conditions predisposing to infections
Severe heart failure- increased mortality

Question 14

TNF-alpha drug interactions

Answer 14

Anakinra- combination can cause serious increase in the risk of infections

Question 15

Adalimumab

Answer 15

TNF-alpha inhibitor

Human IgG antibody to TNF-alpha; binds to TNF-alpha such that it cannot bind to its receptor- does not bind to TNF-beta

Question 15

Infliximab

Answer 15

TNF-alpha inhibitor
Chimeric monoclonal antibody combining portions mouse and human IgG directed against TNF-alpha; binds to TNF-alpha such that it cannot bind to its receptor- does not bind to TNF-beta
Increases risk of lymphoma

Question 17

Etanercept

Answer 17

TNF-alpha & beta inhibitor
Fusion protein containing the ligand-binding portion of the p75 TNF receptor linked to the Fc portion of human IgG
Binds to TNF-alpha & beta forming inactive complexes and preventing it from interacting with cell-surface TNF receptors and thereby activating cells

Question 18

Anakinra MOA

Answer 18

Human IL-1 receptor antagonist (IL-1ra)

Question 19

Anakinra adverse effects

Answer 19

Injected subcutaneously- can cause erythema, pain, and pruritus at site
Increased infection risk

Question 20

Anakinra drug interactions

Answer 20

TNF-alpha inhibitors

Question 21

Anakinra contraindications

Answer 21

Active infections, history of recurring infections or conditions predisposing to infections

Question 23

Prednisone in rheumatoid arthritis

Answer 23

Glucocorticoid
In rheumatoid arthritis they rapidly relieve the symptoms and slow bone erosions
Used as bridging therapy (while classic DMARDs are taking effect)
Continuous low dose therapy
In short term high dose burst to control flares
Locally (intraarticular injection) when flares involve only a few joints