Drugs for Rheumatoid Arthritis and Gout Flashcards
What are some of the drugs used to alleviate joint pain?
- NSAIDs
- Analgesics
- Glucocorticoids
What are the Disease-Modifying Anti-Rheumatic Drugs (DMARDS)?
- Methotrexate
- Hydroxychloroquine
- Sulfasalazine
- Leflunomide
Hydroxychloroquine Indication
Anti-malarial drug that is moderately effective for mild Rheumatoid Arthritis
Hydroxychloroquine MOA
a) inhibition of TLR signaling in dendritic/B cells
b) inhibition of antigen presentation to T cells
Hydroxychloroquine SE
Rare ocular toxicity
Hydroxychloroquine and Pregnancy
Safe during pregnancy and lactation
Sulfasalazine MOA
Thought to interfere with T and B cell immune responses - possibly inhibits activation of NF-B transcription factor
Sulfasalazine and Pregnancy
Safe during pregnancy
Sulfasalazine SE
- Agranulocytosis within 2 weeks - very rare
- Hepatotoxicity
Methotrexate MOA
Indirectly increases the production of adenosine which exhibits known immunosuppressive properties
• decreases the appearance of new bone erosions
• improves the long term clinical outcome.
Methotrexate Indications
Active rheumatoid arthritis that is moderate to severe
Methotrexate SE
- Dose related hepatotoxicity
- Bone marrow suppression
- Increased risk of lymphoma
- Pulmonary toxicity
Methotrxate Contraindications
- Pregnancy
- Renal Disease
- Liver Disease
Leflunomide Indications
- alternative for those unable to take, or non-responsive to MTX
- low cost alternative to TNF inhibitors, or those with a preference for oral medications
Leflunomide MOA
- Inhibits the enzyme dihydroorotate dehydrogenase - uridine synthesis (building block of RNA) - leads to G1 cell cycle arrest
- Inhibits both T cell proliferation and the production of autoantibodies by B cells
Leflunomide SE
- Hypertension - especially with concurrent NSAIDs
- Diarrhea, nausea and rash
- Hepatoxicity - more severe with concurrent methotrexate
Leflunomide Contraindications
- Pregnancy/Breast feeding
- Pre-existing liver disease
What are the TNF-alpha inhibitors?
- Etanercept
- Infliximab
- Adalimumab
Etanercept/Adlimumab/Infliximab MOA
Binds to TNF-alpha and prevents its interaction with its receptor
Etanercept/Adlimumab/Infliximab Indications
Active RA
Etanercept/Adlimumab/Infliximab SE
- Increased risk of infections
- Potential reactivation of latent tuberculosis and latent HBV
- RARE exacerbation of pre-existing congestive heart failure
- RARE development of demyelinating disorders
Etanercept/Adlimumab/Infliximab Contraindications
Treatment should be discontinued if a serious infection or sepsis develops - not for patients with acute or chronic infections
Abatacept Indications
Active RA - used in pts not responsive to TNF-alpha inhibitors
Abatacept MOA
Binds CD80/CD86 Blocks T cell co-stimulation via CD28
Abatacept SE
Increased risk of serious infections - screen for TB and HBV
Abatacept Contraindications
Should not be given in combination with a TNF- blocker or to patients with infection
Rituximab Indications
Active RA - Effective in patients not responsive to TNF-alpha inhibitors
Rituximab MOA
Binds to CD20 on B cells and leads to the depletion of B cells
Rituximab SE
- Increased risk of infection
- Progressive multifocal leukoencepalothapy (PML) -> RARE
- Reactivation of latent viruses
Effects not seen for 3 months, although effects may last 6 months - 2 yrs following a single infusion.
Rituximab
Anakinra MOA
IL-1 receptor antagonist
Anakinra Indications
Active RA
Anakinra SE
- Increased risk of neutropenia
- Increased risk of serious infections
- Increased risk of malignancy
Anakinra Contraindications
Should not be given to patients with acute/chronic infections
Tocilizumab Indications
Active RA in pots non-responsive to TNF inhibitors or in combination therapy with MTX (methotrexate)
Tocilizumab MOA
IL-6 receptor antagonist
Tocilizumab SE
- Increased risk of bone marrow suppression
- Increased risk of serious infections -> TB and HBV
- Hepatotoxicity
- Increased levels of cholesterol
- Increased risk of malignancy
Tocilizumab Contraindications
- Patients with acute/chronic infections
- Patients with pre-existing liver disease
- Patients with low blood counts
***Should not be combined with other Biologics - none of the biologics should be combined
Tofacitinib Indications
Active RA
Tofacitinib MOA
Small molecule inhibitor that inhibits JAK tyrosine kinases involved in immune cell cytokine signaling
Tofacitinib SE
- Lymphocytopenia, neutropenia and anemia
- Increased risk of serious infections including TB
- Increased cholesterol
- Increased liver enzymes
Tofacitinib Contraindications
Not for pts with acute/chronic infections
What are tophi?
Urate crystal deposits around the joint that promote inflammation and joint destruction
Indications of NSAIDs in Gout
Decreases pain and disability due to acute gouty attack
Colchicine Indications
Acute Gouty Attack
Colchicine MOA
Inhibits tubulin polymerization which blocks leukocyte migration/phagocytosis
Colchicine SE
Very narrow therapeutic window and almost always causes vomiting, nausea and diarrhea
Does colchicine have analgesic effects?
No
What type of drug is probenicid?
Uricosuric - increases uric acid excretion
Probenecid Indications
Chronic gout due to decreased uric acid excretion
Probenecid MOA
Weak organic acid inhibits anion transporters in the proximal renal tubules involved in the reabsorption of uric acid
Probenecid SE
Can cause kidney stones
Probenecid Contraindications
- Kidney stones
- Renal insufficiency
- Uric acid overproduction
When should probenecid NOT be given?
Should not be given until 2-3 weeks after the initial attack - drug can actually initiate and/or prolong the symptoms of an acute gouty attack
Why does probenecid have many DDIs?
It inhibits the URAT1 transporter, which many drugs (ex: indomethacin, naproxen, lorazepam, cephalosporins, methotrexate, captopril, AZT and ganciclovir) utilize for reabsorption.
What are the xanthine oxidase inhibitors?
- Allopurinol
- Feboxostat
Allopurinol/Feboxostat Indications
Used in the treatment of chronic gout to block overproduction of uric acid
- Good for patients with a history of uric acid kidney stones
Allopurinol/Feboxostat MOA
Inhibits xanthine oxidase
Allopurinol/Feboxostat SE
- Rash, leukopenia, thromobocytopenia & fever can occur in 3-5% of patients
- RARE SE is allopurinol hypersensitivity syndrome (only in allopurinol)
Allopurinol Hypersensitivity Syndrome
- potentially life threatening reaction (25% mortality rate)
- symptoms include: erythematous rash, fever, hepatitis, eosinophilia and acute renal failure
- most likely to occur in patients taking excessive doses of drug in the presence of pre-existing renal failure and/or use of diuretics
What ethnicities are at increased risk of allopurinol hypersensitivity syndrome?
Han Chinese, Korean and Thai
What are the main DDIs of allopurinol/feboxostat?
6-mercaptopurine and azathioprine - have increased toxicity as their metabolism is inhibited (xanthine oxidase is inhibited)
Pegloticase Indications
Advanced, actively symptomatic gout - uncontrolled with other uric acid lowering drugs
Pegloticase MOA
Porcine uricase linked to PEG (polyethylene glycol) and the pig uricase enzyme allows for conversion of uric acid to a soluble metabolite
Pegloticase SE
Generally well tolerated but generation of anti-drug antibodies limits treatment
What prophylaxis does pegloticase require?
Requires NSAID/Colchicine prophylaxis
