LOCO EOYS2 Flashcards
Pharmacological managementfor OA
COME BACK
- Start with oral analgesics &/ or topical NSAIDs
- Where paracetamol or topical NSAIDs are ineffective then substitute with oral NSAID/COX-2 inhibitor
- Intra-articular injections; Corticosteroid injections
OA
Why are only three intra-articular injections (corticosteroid injections) recomended?
If prescribe too much: softens cartilage which can cause further problems
State 6 surgical interventions for OA [6]
Arthroscopic lavage
Arthroscopic lavage plus debridement
Microfracture
Mosiacplasty (osteochondral transplant)
Chondrocyte grafts
Joint replacement
Explain mechanism of Arthroscopic washout and debridement plus microfracture [2]
Same mechanism as arthroscopic washout and debridement
After debridement: have area of exposed bone: drilling into subchondral bone and bone marrow pluripotent stem cells
Stimulates repair of articular cartilage
Cartilage recovers within 4-6 months
Explain the MoA of chondrocyte grafting
Take chondrocytes from other areas of the body (e.g. costochondral joint)
Grow chondrocytes in culture
Place in graft and get more hyaline cartilage
OA treatment
Explain MoA of mosaicplasty (osteochondral grafting) [1]
Take undamaged cartilage from less weight bearing regions plus the underlying bone and move to OA region
OA treatment
Adalimumab targets which cytokine? [1]
TNF inhibition
State three locations of chondrocytes for chondrocyte grafting [3]
Rib costochondral process
Non damaged part of joint
Also cartilage implants from young individuals available
Gout is a disorder of metabolising which substance? [1]
What does this mean has deposition in soft tissue? [1]
Uric acid metabolism disordered: causes monosodium urate crystals get deposited in soft tissues
What is a podagra? [1]
gout which affects the joint located between the foot and the big toe; metatarsophalangeal joint.
Explain a complication of gout in another organ [1]
Renal damage and kidney stones:
- Chronic urate nephropathy in patients with chronic tophaceous gout can result from the deposition of urate crystals in the medullary interstitium and pyramids, resulting in an inflammatory reaction that can lead to fibrotic changes.
How does synovial fluid gout appear? [1]
If did a smear of gout synovial fluid what cell type would be present? [1]
White & iridescent - although not always present like this if there arent enough crystals
There is also a predominance of polymorphonuclear neutrophils (PMNs).
Describe the pathophysiology of gout
Sudden increase in the number of crystals and the body isn’t able to respond by coating crystals with serum proteins
Uncoated crystals in the joint that triggers an attack.
Naked urate crystals are then believed to interact with intracellular and surface receptors of local dendritic cells and macrophages, serving as a danger signal to activate the innate immune system
This interaction may be enhanced by immunoglobulin G (IgG) binding.
(Triggering of these receptors, including Toll-like receptors, NALP3 inflammasomes, and the triggering receptors expressed on myeloid cells (TREMs) by MSU) results in the production of interleukin (IL)–1, which in turn initiates the production of a cascade of pro-inflammatory cytokines, including IL-6, IL-8, neutrophil chemotactic factors, and tumour necrosis factor (TNF)–alpha
Neutrophil phagocytosis leads to another burst of inflammatory mediator production
Describe the role of neutrophils in gout pathogenesis
- Sudden increase in MSU uncoated crystals cause neutrophils to enter synovial fluid
- Neutrophils phagocytose MSU crystals, and macrophages that detect crystals release IL-1
- .The structure of MSU crystals cause neutrophil to be pierced, lyse and die
- Contents of neutrophil released: proteins, etc which bring more white blood cells in, and production of pro-inflammatory cytokines
- Acid released from neutrophils lowers pH, makes crystals precipitate even more: attack will start of pain, etc
- This inflammation from neutrophil phagocytosis is also aided by massive release of IL-1 from original macrophages that come into contact with crystal, which initiates a cascade of release of other cytokines like TNF-alpha, IL-6, IL-8, etc.
Gout is common in patients with which syndrome? [1]
metabolic syndrome
presence of these associated disorders can lead to coronary artery disease, these problems should be sought and treated in patients diagnosed with gout.
Importantly, ask about a history of peptic ulcer disease, renal disease, or other conditions that may complicate the use of the medications used to treat gout.
Explain the three mechanisms of gout development [3]
Purine overproduction:
* This occurs when there is increased cell turnover or lysis of cells leading to release of purines and breakdown to uric acid.
* Causes include myelo- or lymphoproliferative disorders, psoriasis and use of chemotherapy agents.
Increase purine intake:
* There are several foods and beverages that are rich in purines and increase the risk of developing gout.
* These include seafood (i.e. anchovies, sardines), red meat, alcohol and fructose-rich beverages.
Decreased uric acid secretion:
* Uric acid is predominantly renal excreted so anything that affects the kidneys can increase the risk of developing gout.
* Causes include diuretics (i.e. furosemide), acute kidney injury, chronic kidney disease, ACE inhibitors and diabetes mellitus
State two drug classes that could cause decreased uric acid secretion [2]
Name a disease that could cause high turnover of cells and therefore increased purine production [1]
Diuretics: Loop and Thiazide like
psoriasis
How would you treat acute gout / gout attack? [4]
NSAIDs:
* Start with highest dose for 2-3 days & taper down over 2 weeks
Colchicine:
* 2nd line (narrow therapeutic window and risk of toxicity)
Corticosteroids
* For those that can’t use NSAID or colchicine
IL1 biologicals
* Rilonacept, canakinumab, anakinra
* Reduces length of attack and reoccurrences
* Used for patients who have severe and frequent flares
Which IL1 biologicals can be used to treat acute gout? [3]
Rilonacept, canakinumab, anakinra
Describe the pathogenesis of rat-bite erosions
rat-bite erosions are due to osteoclasts eroding the bone in joints with gout
TNF-alpha, IL-1, etc will convert synovial macrophages to osteoclasts
The crystals tend to get lodged in the deeper folds of the joint capsule, meaning the osteoclasts will attack the shaft of the bone
Describe how you treat chronic gout [5]
Allopurinol:
* Blocks xanthine oxidase, which is responsible from converting xanthine (which comes from purines in the diet) to urate
Febuxostat:
* non-purine selective inhibitor of xanthine oxidase
uricosuric:
* increases uric acid excretion
Probenecid:
* increases the secretion of uric acid
* fewer side effects than allopurinol.
Rasburicase:
* Catalyses conversion of uric acid to allantoin
Which ARB can be used to treat chronic gout? [1]
Losartan
Describe the pathogenesis of pseudogout [2]
Deposition of calcium pyrophosphate in and around joints onto the surface of the articular cartilage and the fibrocartilage:
- Release of calcium pyrophosphate crystals into the joint space
- followed by neutrophils, macrophages etc phagocytosing the crystals: cytokine release and inflammation.
- The crystals are not as shiny or sharp/needle like, meaning they don’t cause NETosis and the attack is much milder, with a slower onset.
Which is the most commonly affected joint by pseudogout? [1]
Knee is most commonly affected joint but can affect any joint
Describe how cholesterol crystals are made [1]
Defective drainage of synovial fliud back into the venous system due to synovitis, local destruction, increased permeability of synovial membrane to LDL and HDL & intraarticular bleeding
This sign is suggestive of
Osteoarthritis
Gout
Pseudogout
Rheumatoid arthritis
Osteoporosis
Rheumatoid arthritis: Bakers cyst
Name drug A used to treat osteoporosis [1]
Denosumab
Name drug A used to treat osteoporosis [1]
Teriparatide
Name two bones that are more likely to suffer from osteoporosis [2]
Vertebral bodies
Femoral neck
What is first line treatment for osteoporosis? [1]
Describe MoA [3]
Bisphosphonates:
- inhibits osteoclast activity
- promotes osteoclast apoptosis
- Decreases RANKL expression (so osteoblasts don’t turn into osteoclasts [?])
Describe complications of bisphosphonates
Kills off osteoclasts: don’t remove old bone: thickened bone
Get giant osteoclasts: poisoned osteoclasts
Osteonecrosis occurs
Descibe pathophysiology of Pagets disease [2]
Describe the three phases of Pagets disease [3]
(Theory) osteoclasts: may be infected with a virus that alters them AND genetics
Phases:
1. increased rate of bone resorption:
* large number of giant osteoclasts
2. Compensatory phase / proliferative:
* increased bone formation & accelerated depostion in disorganised manner
3. Burnt out phase: sclerotic:
* Hyper-vascular bone marrow; Bone hypercellularity may diminish leaving dense “Pagetic bone”
Which nerve is at risk here? [1]
median
SLE
Colchicine - inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
Draw a flow chart for diagnosis of joint pain
Describe three neuromuscular complications of RA [3]
Muscle wasting
Carpal tunnel syndrome
Atlanto-axial subluxation: odointal peg impinges on the spinal cord
Describe the symptoms of SLE
90% of patients have arthritis:
* symmetrical small joint polyarticular arthiritis (most common)
* jaccoud arthropathy (rare)
* avascular necrosis
Fatigue
Weight loss
arthralgia
myalgia
fever
butterfly rash: gets worse with sunlight
shortness of breath
hair loss
