Arthritis Flashcards
Is Rheumatoid arthritis organ specific?
It’s Non-organ specific
What is osteoarthritis?
Caused by wear and tear of joints causing inflammation
Non-inflammatory disorder (use of synovial joints)
Characterised by cartilage loss
Affects knees, hips + small hand joints
Link to obesity
Describe the pain in osteoarthritis
Worsened by movement
Eased by rest
Worse at the end of the day
Commonly affects:
- hands
- knees
- spine
- hips
Unilateral (affect only one joint e.g. left hand only)
What are the treatment options for OA?
Steroid injections
NSAIDs / Cox-2 inhibitors
Surgery - knee replacement
Mechanism of NSAIDs
NSAIDs inhibit COX enzyme
NSAID use in Osteoarthritis treatment
In Arthritis, NSAIDs block cyclooxygenase enzymes (particularly COX-2) which reduces inflammation, pain + stiffness
COX enzymes convert arachidonic acid to prostaglandins
How + when do we take corticosteroids injections + what drugs are used
Intra-articular (into joints)
When pain is moderate to severe
Drugs:
- triamcinolone
- methylprednisolone
Can cause cartilage injury + loss
What is Rheumatoid Arthritis?
Autoimmune disease in which the body’s immune system attacks the joints causing chronic inflammation.
Signs of RA
Joint damage
Muscle wastage
Deformity
Symptoms of RA
Pain
Stiffness
Joint swelling
Joint deformity
Blood lab tests for RA
WBCs = INCREASED
Erythrocyte sedimentation rate (speed at which your red blood cells clump and fall together to the bottom of a glass tube within an hour) = INCREASED
Anaemia
Rheumatoid factor (group of proteins your body creates when your immune system attacks healthy tissue - Antibodies to IgG) = INCREASED
Risk factors of RA
Age
Gender - women developing premenopausal
Post-partum
Stress
Genetics - if one twin has, the other is 20% likely
Smoking
Describe the pain in Rhematoid Arthritis
Improves movement
Worse on waking
Affects small joints
Affects bilateral joints
What is Rheumatoid disease?
Systemic disease (affects many organs or body as a whole) that affects:
- Especially at the joints
- Eyes inflammed (50%)
- Skin
- Vasculitis - destroy group of blood vessels
- Lungs
- Salivary glands (reduced)
- Pericarditis (inflammation of pericardium)
What are the type of treatment options for RA?
Symptomatic relief
- Analgesia to reduce need for NSAIDs
- NSAIDs (+ PPI)
Slow progression
- DMARDs
- Steroids
- Biologicals
Monitor effectiveness
Function of DMARDs
(Disease modifying anti-rheumatic drugs)
Directly inhibits cell proliferation
(inhibit wide variety of cytokines including interleukins, interferons + TNFalpha)
Slow-acting (may take months for benefits to become apparent)
No analgesic activity
Used for rheumatic disorders + where inflammation does not respond to COX enzyme inhibitors
Slows course of disease
Treatment lines of DMARDs
1st LINE - Start w/ combination therapy (MTX + 1 other DMARD)
2nd LINE - Mono therapy w/ rapid dose titration
Slow onset of action - take up to 3 months
Used with glucocorticoids until effective (shouldn’t be used long term)
Counselling points when using DMARDS
Dose increased gradually
Improvement takes a few months
Monitoring is necessary
Nausea
Signs of:
- Blood dyscrasias (formed elements in blood) = sore throat, tiredness
- liver toxicity = jaundice
- lung toxicity
Bone toxicity
Perform LFTS, FBC + U+E before + during treatment
What are the drugs in DMARDs?
Methotrexate = 1st choice
Sulfasalazine
Leflunomide
IM gold
Function of Methotrexate
Dihydrofolate reductase inhibitor
(pyrimidine synthesis = inhibits DNA/RNA synthesis)
Immunosuppressant
Commonly used
Dose - 7.5-25 micrograms
Weekly dosing
What causes autoimmune diseases
Autoimmune diseases is when your immune system attacks its own cells
Leads to tissue damage
Genetic factors can influence it
Can be influenced by pregnancy, infection, diet + environment
When do you start on DMARDs?
Within 3 months
When do we reduce dose of DMARDs?
Reduce to a dose when symptom control has been achieved
What do patients need to take with Methotrexate
Folic acid
To prevent side effects
Folic acid does not prevent inflammatory effects of methotrexate
Name other mechanisms of methotrexate in rheumatoid arthritis
Folic acid antagonism
Cytokine alteration
Adenosine signalling
Generation of reactive oxygen species
Effects of eiocosanoids + matrix metalloproteases
Effects of methyl donors
Counselling points of MTX
WEEKLY DOSE
Take folic acid as directed = ONCE WEEKLY but not on the same day as MTX
Regular blood tests
Recognise + report signs of serious side effects
Contraception = avoid pregnancy due to birth defects
Patients given patient information book about MTX
Injectable methotrexate - cytotoxic, sharps bin, disposal etc
ADME of Methotrexate
Absorption unaffected w/ age
Decreased metabolism + excretion w/ age
Increased risk of toxic effects
NSAIDs interaction - avoid OTC - renal toxicity - reduced excretion of MTX
What is Sulfasalazine (SFZ)?
Immunosuppressant
500mg OD
Increased weekly - max. 2-3 grams per day in divided doses
Onset of action is 6 weeks
What are the side effects of Sulfasalazine?
GI intolerance - nausea + vomiting
Blood disorders - bruising + unexplained bleeding
Discolouration of urine + contact lenses (happen in the first 3-6 months)
Function of Leflunomide
Immunosuppressant
Metabolised to teriflunomide
Inhibits dihydroorotate dehydrogenase (involved in pyrimidine synthesis, inhibiting DNA synthesis)
What are the adverse effects of Leflunomide?
Diarrhoea
Nausea, rash, alopecia
Abnormal LFT
Teratogen
- contraception including male treatment
- additional 2 years post stopping treatment
- present in breast milk
Function of Hydroxychloroquine
Used in mild/moderate cases
Alternative 1st line drug
Inhibit lymphocyte function
Long half life
Function of Gold
Immunosuppressant
e. g. sodium aurothiomalate (deep intramuscular)
e. g. auranofin (oral)
2nd/3rd line treatment
Weekly until response
Rashes, blood disorders
Other types of DMARDs
Pencillamine - penicillin metabolite
Cyclosporine - T-cell function (severe RA)
Azathioprine - inhibit purine synthesis
Only relieve symptoms - do not modify disease progression so less used
Describe the use of Steroids in RA
Used orally for flare/exacerbations of RA
Bridging therapy = between starting/switching to reduce symptoms (rapid symptom control)
IM, IA, IV (IV can be toxic)
What are the oral steroids used in RA?
Prednisolone
Can’t be used long term
Side effects:
- osteoporosis = bone protection
- PPI`(for long-term therapy)
Anti-TNFalpha therapy in RA
Block TNFα which reduce inflammation and joint damage
Licensed for moderate-severe RA where response to other DMARDs is inadequate
Alone/w/MTX
MONOCLONAL ANTIBODIES
Adalimumab - 40mg SC alternate weeks
Infliximab - 3/mg/kg IV @2,6 then 8 weeks
Etanercepts - 25mg SC TWICE WEEKLY
Name a interleukin-1 inhibitor used for RA
Anakinra = IL-1RI antagonist
IL-1 = pro-inflammatory cytokine which mediates many cellular responses including synovial inflammation (joints)
Injection site reactions
NICE rejected due to weak efficacy
Name a new drug for use in RA
Tofacitinib
Janus Kinase inhibitor
Janus kinase involved in cytokine signalling + gene transcription
NICE accepts if price reduces
What is Abatacept?
Drug used to treat autoimmune diseases e.g. rheumatoid arthritis
This is by blocking B7 binding to CD28
NICE not recommended due to cost
