Arthritis Flashcards
(38 cards)
1
Q
Is rheumatoid arthritis an organ-specific or non-organ specific autoimmune disease and where does it affect?
A
Non-organ specific; systemic disease affecting:
- joints (emphasis)
- eyes (50% of the time; inflammation)
- skin (nodules)
- vasculitis
- lungs
- salivary glands (reduced secretion)
- pericardium (inflammation of lining of the heart)
2
Q
What causes RA?
A
- Antibodies against “self”; own proteins targeted
- Genetic factors
Can be precipitated by:
- Pregnancy
- Infection
- Diet(?)
- Environment(?)
Leads to tissue damage.
3
Q
How does autoimmune disease develop?
A
- Autoantigens present in everyone
- But self-tolerance prevents autoantigens activating the immune system (immune system recognises own antigens being targeted so allows it)
- Thus not everyone develops autoantibodies to autoantigens; and of those that do, not everyone develops autoimmune disease from autoantibody production
- In autoimmune disease, self-tolerance is lost leading to attack of “self”
4
Q
What is osteoarthritis and how is it characterised?
A
- Primarily non-inflammatory disorder (synovial joints being worn)
- Characterised by cartilage loss
- Thus grinding of bone; prostaglandin release as a result resulting in pain (can bring about inflammation)
5
Q
Where does OA most commonly affect and what is it linked to?
A
- The knees/hips/small hand joints/spine
- Linked to being overweight/obese (more weight = more risk)
6
Q
What aggravates/eases pain in OA?
A
- Worsened by movement
- Eased by rest
- Worse at the end of the day (with use of joints throughout)
- Usually unilateral
7
Q
What are the treatment options for OA?
A
- Pain (treat)
- Steroid injections (reduces PGA)
- NSAIDs/COX-2 inhibitors (reduces PGA)
- Surgery
8
Q
Which COX pathway(s) do NSAIDs block and what are the consequences?
A
- NSAID for inflammation
- COX-1 involved in PG production in GIT
- COX-2 involved in inflammation
BUT NSAIDs block both COX-1 and COX-2 pathways (selective COX-2 would treat pain w/less GI disturbances but alas less protective effective of PGAs seen with NSAIDs)
9
Q
When are corticosteroids injections used for SA and how do they work?
A
- When pain is moderate to severe
- Inhibits PLA-2 (phospholipase A2) thus reducing PGA production
10
Q
Where are corticosteroid injections administered and why?
What are their possible side effects?
A
- Injected directly to book the as blood flow to joints is poor
- Possibly caused further cartilage injury and loss though
11
Q
What is rheumatoid arthritis and how is it characterised?
A
- Chronic inflammatory disorder
- Autoimmune disease
- Characterised by joint damage, muscle wastage, deformity (stiffness from not using joints as much)
12
Q
What are the symptoms of RA?
A
- Pain
- Stiffness
- Joint swelling
- Joint deformity
13
Q
How would WBC count, ESR (erythrocyte sedimentation rate) or rheumatoid factor be affected in RA?
A
- WBC; increased
- ESR; increased (in chronic inflammation erythrocytes stick together more thus becoming heavier and sinking; high ESR indicates inflammation)
- Rheumatoid factor present (an autoantibody against the tail portion of the antibody IgG)
14
Q
What aggravates/eases pain in RA?
A
- Pain improves with movement (opposite of OA)
- Worse on waking (opposite of OA)
15
Q
What type of joints does RA affect?
A
- Small joints
- Bilateral joints (affecting both sides of the body thus both wrists etc)
16
Q
What are the aims of RA treatment?
A
- Relieve pain
- Modify/slow down the disease process
(Prevent joint destruction)
(Preserve/improve functional ability) - Multidisciplinary approach
- Treat promptly and introduce DMARDs early
17
Q
What treatment options are available for RA?
A
- Symptomatic relief
(analgesia to decrease need for NSAIDs; use PPI w/NSAIDs if needs be) - Slow progression of disease
(DMARD/steroids/biologicals)
18
Q
What are DMARDs?
When would they be started?
A
Disease Modifying Anti Rheumatic Drugs
- Ideally start within 3 months (start slowing disease progression ASAP)
- Reduce dose (CYTOTOXIC) cautiously when symptom control achieved (if flare-up return to previous established dose)
- Monitoring
- Counselling
19
Q
How do DMARDs work and how long does it take?
A
- Directly inhibits cell proliferation; inhibiting immune cell production (and thus fewer inflammatory mediators)
- Inhibitions of a wide variety of cytokines (signalling/mediators) including: interleukins, interferons and TNF-alpha.
- Slow-acting; may take up to 3/12 (a few months) for benefits to become apparent
- No analgesic activity
20
Q
When are DMARDs used?
A
- Primarily for rheumatic disorders and where inflammation does not respond to COX-inhibition
- Slows course of disease
21
Q
What are DMARDs role in RA therapy?
A
- First line treatment
(combination therapy; methotrexate + 1 other DMARD)
(monotherapy with rapid dose titration; if combination therapy not possible start with MTX and increase dose quickly) - Use with glucocorticoids until effective (type of corticosteroid; start off w/steroid treatment to reduce inflammation and then titrate down dose to zero when DMARD starts working)
22
Q
What are the counselling points for DMARDs?
A
- Dose increased gradually
- Improvement may take some months (patient needs to be aware effect is not immediate)
- Monitoring necessary
- Nausea
- Report signs of blood dyscrasias, liver or lung toxicity.
23
Q
What DMARDs are available for treatment?
A
- ) Methotrexate
- ) Sulfasalazine (Crohn’s)
- ) Leflunomide
- ) IM gold (intramuscular)
24
Q
What is methotrexate and how does it work?
A
- Dihydrofolate reductase inhibitor
- Inhibits pyrimidine synthesis (and thus DNA/RNA)
- Immunosuppressant
- Dose individual to patient; made up each time, titrate to lower dose when effects shown
- Weekly dosing (same day each week, once a week)
25
How does MTX inhibit dihydrofolate reductase (DHFR) and what are the consequences?
- MTX competitively inhibits DHFR (which essential for thymine synthesis)
- MTX 1000x affinity to DHFR than folate
- DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate; thus MTX prevents this conversion leading to less Methylene THF for DNA synthesis
- Affects cells with lots of proliferation; particularly where inflamed thus less inflammation
26
What are the issues with methotrexate toxicity?
- Nausea
- Post dose 'flu'
- Bone marrow toxicity (uncommon)
- Hepatotoxicity
- Teratogenic (affects cell turnover in foetus; contra-indicated in pregnancy)
- GIT effects
- Renal toxicity
- Blood disorders (bruising/unexplained bleeding)
27
Why is taking folic acid with MTX beneficial?
- Folic acid is the synthetic version of folate; what MTX is side-manning
- Rather than being counter-productive taking folic acid when not taking MTX (avoid competitiveness) can reduce other systemic side effects w/o inhibiting the therapeutic effect of MTX
28
What are the counselling points of MTX?
- Weekly dose
- Take folic acid as directed (once weekly or daily but not the same day as MTX)
- Regular blood tests (monitor hepatotoxicity etc)
- Recognise and report signs of serious side effects
- Contraception (teratogenic effects)
- Patient information book for MTX given
- Sharps bin (purple lid for cytotoxicity) and its disposal
29
What are the concerns of MTX and ADME?
- Absorption unaffected with age
- Decreased metabolism and excretion with age
> Thus increased risk of toxic effects
- Interaction with NSAIDs; avoid OTC (do not self-prescribe)
> Renal toxicity
> Reduced excretion of MTX; potentially toxic plasma levels of MTX
30
How does the pro-drug sulfasalazine (SFZ) work in RA and how long does it take?
- Immune suppressant
- Metabolised to 5-ASA inhibiting leukotriene & prostanoid synthesis, scavenges free radicals and decreases neutrophil chemotaxis
- Initially 500mg/day (increased weekly/max 2-3g a day in divided doses)
- Onset of action; 6 weeks
31
How should sulfasalazine be monitored/ADRs to look out for?
- GI intolerance (nausea)
- Blood disorders (bruising/unexplained bleeding - similar to MTX)
- Discolouration of urine & contact lenses (counselling point; advise to wear glasses instead for duration of treatment)
32
How does the immunosuppressant leflunomide work?
- Inhibits dihydroorotate dehydrogenase
- Is itself metabolised to teriflunomide
- Impairs cell proliferation akin to MTX, dampening down immune response
33
What adverse effects are associated with leflunomide?
- Diarrhoea (20%)
- Nausea/rash/alopecia (10%)
- Abnormal LFT (liver function test; 5%)
- Teratogenic
> Contraception, INC. male treatment
> +2 years post-stopping (can't have child for)
> Present in breast milk (use bottled)
34
How does gold work for RA treatment and what adminstration methods are available?
- Immune suppressant
- Sodium aurothiomalate deep IM
- Auranofin (oral); less toxic but less efficacy
- 2nd or 3rd line treatment
- Weekly regimen until response (then extend interval at which it is given)
- Possible rashes/blood disorders
35
When is hydroxychloroquine given and how does it work?
- Used in mild/moderate cases
- Add-on to MTX etc
- Inhibits lymphocyte function
- Long half-life
36
What other DMARDs are available and how do they work?
| Why are they not used as much?
- Penicillamine; metabolite of penicillin (only used by experimental clinicians; toxicity)
- Ciclosporin; severe RA (T-cells affected; usually used in tissue transplantation)
- Azathioprine; inhibits purine synthesis (as seen in Crohn's) thus DNA synthesis
Relieves symptoms but does not modify disease progression so less used.
37
How are steroids used in RA and when/how are they administered?
- Bridge therapy between starting new DMARD/switching to reduce inflammation by blunting immune response
- Rapid symptom control
- IM/IA/IV (better than oral; GI side effects, PGA reduction - PPI would be required)
- IV possibly more toxic
38
What oral steroid can be used/what precautions should be made?
- Prednisolone
- Conflicting evidence; long term use is discourages
- Side effects present:
> Increases risk of osteoporosis (calcium supplements to prevent bone degradation)
> PPI needs to be given to protect stomach as PGA is reduced
