4B. Arthritis and Gout Flashcards
Monoclonal Antibody Antagonists: infliximab and adalimumab
• These biologics are large proteinaceous compounds that have to be administered through ____, either
subQ or IV infusion
◦ In targeting TNF (cytokine released by activated macrophages, which then affect T cells)
‣ TNF diffuses through cells -> bind to TNF receptor on the target cell
◦ The approach used in development of infliximab and adalimumab -> develop a ____
that can bind TNF -> it worked!
‣ Inject adalimumab ____ every 2 weeks and it leads to a dramatic improvement in ____
‣ For infliximab the ____ version is administered every 4-8 weeks and works well
injection monoclonal antibody subQ RA IV
TNF-α Receptor-based Antagonist: etanercept
In addition to there being membrane bound TNF receptors, there are also soluble receptors In the development of etarnercept…
◦ Took the ____ portion of an antibody and covalently bound two of the ____ TNF receptors to generate etanercept -> can bind TNF
◦ Administered ____ once a week
Fc
soluble
subQ
TNF-α antagonists
IV: ____ (Remicade, Inflectra, Remsima) [every 4-8 weeks] golimumab (Simponi Aria) [every 8 weeks]
Subcutaneous: \_\_\_\_ (Enbrel) [every week] adalimumab (Humira) [every other week] golimumab (Simponi) [every 4 weeks] certolizumab pegol (Cimzia) [every 2 or every 4 weeks]
Adverse reactions: ____ infections (TB, fungal), risk of severe infections, upper respiratory tract infection, Lupus-like syndrome, demyelinating central nervous system disorder, worsening congestive heart failure, ____ cancer, liver injury, Hepatitis B reactivation, injection site or infusion reactions (erythema, itching, swelling)
Monitor: ____, CBC, (check for TB before starting)
infliximab etarnercept opportunistic skin LFTs
tofacitinib (Xeljanz)
- “small molecule” inhibitor of ____. Inhibition of JAK disrupts ____ signaling, interfering with gene transcription and cytokine production
- For use in moderate to severe ____ in people who had an inadequate response to ____. Can be used a mono therapy or with non biologic DMARDs
Route: by ____
Dosage: 5 mg PO twice daily or 11 mg PO once daily
Metabolism: 70% hepatic ____ and 30% renal excretion of parent drug
Adverse Reactions: ____, liver enzyme elevation, ____, anemia, thrombocytopenia, cholesterol increase, serious: opportunistic infection (TB, fungal), GI perforation, malignancy
Monitor: ____, LFTs, cholesterol levels
janus kinase
intracellular
RA
MTX
mouth
metabolism
infection
neutropenia
CBC
Corticosteroid and DMARD Conclusions
1. DMARDs are started early in an attempt to prevent ____ destruction in RA.
- Most DMARDs require ____ before their effects are seen. NSAIDs and corticosteroids are used as a ____ therapy.
- DMARDs with different mechanisms of action are sometimes combined. However, ____ toxicities can occur (typically to the bone marrow, liver and kidneys) and these must be considered and monitored.
- ____ now is often the initial drug of choice for RA. Leflunomide, hydroxychloroquine, sulfasalazine are also commonly used.
- ____ are biologics that are generally very effective and well tolerated in the treatment of RA.
- Many DMARDs cause ____ and predispose to infection. Prior to any major surgical interventions, communication between the oral surgeon and rheumatologist is indicated to discuss the role of withholding the DMARD at the time of surgery. The use of additional ____ may also be considered.
- Corticosteroids should rarely be stopped abruptly as this can lead to ____ insufficiency. For major surgical interventions, patients may actually need more ____ at the time of surgery (“stress dose steroids”) to prevent the symptoms of adrenal insufficiency.
joint
months
bridge
additive
methotrexate
TNF-alpha
immunosuppression
antibiotics
adrenal
steroids
Osteoarthritis (OA)
The most common arthritis. It is ____.
noninflammatory
OA
- Most ____ form of arthritis
- Two thirds of those over 65 have radiographic evidence of OA
- May be ____ or generalized
- A leading cause of ____ and pain in the elderly
- Accounts for one in eight days of ____ activity in elderly
common
localized
disability
restricted
OA
- Typically ____ arthritis on exam (usually no warmth or redness)
- ____ response occurs during injury but is not the primary pathogenic mechanism in OA
- Inflammation is the result of ____ breakdown rather than the cause
non-inflammatory
inflammatory
cartilage
• Prevalence of OA as a function of age -> OA increases with ____
age
Joint distribution
Where does OA occur?
Common in hands, but it tends to spare the joints where RA goes
◦ RA: ____ and ____ joints
◦ OA: ____ (farthest out on your finger) and the bottom of the thumb where it
attaches to the wrist
‣ Can involve the ____ as well, can lead to a little confusion when trying to figure if the patient is developing just OA, or RA (and you can have both at the same time) The spine (cervical and lower spine) are typical areas
◦ Over the age of ____ will find OA here
Hips, knees can be locations
Also where the big toe attaches to the foot -> the ____
MCP
PIP
DIP
PIP
50
first metatorsophalangeal joint
OA Pathophysiology
- Gradual loss of ____ cartilage
- Thickening of ____ bone
- Bony outgrowths at ____ margins
- Mild, chronic ____ synovial inflammation
articular
subchondral
joint
nonspecific
Joint Anatomy
- In RA it was the ____ was the problem
- In OA it’s the wearing out of the ____ cartilage
synovium
articular
One of these knees is not like the other…
• Knees -> one is swollen, and just looking at it you wouldn’t be able to tell it’s due to OA or an inflammatory arthritis unless you felt it, took fluid out or took an ____
x-ray
Normal Knee
• X-ray of a normal knee -> the bones come together and you have a gap -> ____ (doesn’t show up on the x-ray)
articular cartilage
OA: Medial and Lateral Cartilage Degeneration
• In OA, we have two different knees
• Knee on the right (we have cartilage on the left, but on the right side it’s dramatically reduced), the bone is
____ on the right side -> goes along w increased density of the bone on this side
◦ Can see ____ developing at the joint margin (points along this side)
• Knee on the left: the medial joint space has been lost with what appears to be an ____ density of bone on this side with some ____ developing
◦ Same example of the knee on the right…
brighter
spurs
increased
spurs
OA: Cartilage Defect on Arthroscopy
• Take a look in that joint with an arposcope -> can see cartilage that should be smooth is actually ____, and you might be able to see ____ the cartilage to the bone
not
through
