Pharmacology - Arthritis Flashcards
Automimmune disease causes
-antibodies against self (loss of self-tolerance)
-lead to tissue damage
-genetic factors
-can be precipitated by:
pregnancy, infection, diet, env?
Osteoarthritis characteristics
- cartilage loss
- most commonly affects knees, hips and small hand joints
- link to overweight/obesity
Pain in OA
- worsened by movement
- eased by rest
- worse at the end of the day
- knees, hands, spine, hips
OA treatment
Painkillers
Steroid injections
NSAID/COX2 inhibitors
Surgery
COX1 vs. COX 2
COX1: PG production in GIT
COX2: involved in inflammation
Intra-articular
- corticosteroid injection into joints
- when pain is moderate to severe
- can casue cartilage loss and injury –> do NOT use long-term
Rheumatoid Arthritis
-chronic inflammatory disorder
Rheumatoid Arthritis signs and symptoms
joint damage/swelling muscle wastage joint deformity pain stiffness
RA lab results
- elevated WBCs
- faster erythrocyte sedimentation rate (ESR)
- anemia
- rheumatoid factor (antibodies to lgG)
Epidemiological risk factors
- age (peak at 65-75)
- gender (before menopause age, more females)
- post-partum
- stress
- genetic
- smoking
Pain in RA
- improves with movement
- worse on waking
- affect small joints
- affect both sides of body (bilateral joints)
Rheumatoid disease
- systemic disease
- eyes (50%)
- skin nodules
- vasculitis
- lungs
- salivary glands (reduced)
- pericarditis (inflammation of pericardium)
RA treatment
symptomatic relief:
- analgesia to reduce need for NSAIDs
- NSAIDs + PPI
slow progression:
- DMARD
- Steroids
- Biologicals
DMARDs stand for?
Disease Modifying Anti Rheumatic Drugs
DMARDs for RA
- ideally start within 3 months
- toxic: increase gradually then reduce cautiously when symptoms are controlled
- no analgesic effect but ease pain due to less inflammation
DMARDa therapy
first line:
- combination therapy (methotrexate + 1 other)
- monotherapy with rapid dose titration
slow onset of action
used with glucocorticoids until effetive
DMARDs counselling
- improvement may take a few months
- measue LFTs, FBC and U&E levels before treatment
- continue to monitor
- toxicity: lower dose
- inflammation: increase dose
DMARDs examples
methotrexate
sulfasalazine
leflunomide
IM gold
Methotrexate mechanism and side effects
- dihydrofolate reductase inhibitor
- immunosuppressant
- dose individual to patient
- take weekly NOT daily
- folic acid supplements (does not negate methotrexate anti-inflammatory effect)
- pregnant no
- GIT effects
- post-dose ‘flu’ (more common with oral)
MTX Counselling
- weekly dose
- folic acid not same day as MTX
- regular blood tests
- report side effects
- contraception
- patient information book about MTX
- injection: sharps bins, disposal
MTX ADME
- dec. metabolism andexcretion with age
- ADR with NSAIDs
Sulphasalazine
- immunosuppressant
- onset: 6 weeks
- initially 500mg/day, inc daily, max 2-3g/day in divided doses
- GI intolerance (nausea)
- discolouration of urine and contact lenses
Leflunomide
-immunosuppressant
Leflunomide ADR
- GI side effects
- teratogenic (male also) +2 years after stopping, present in breast milk
Steroids in RA
- im, ia, iv
- bridge between starting/switching DMARDs
- rapid symptom control compared with DMARDs
Biologicals
TNFα-Blockers
- licensed for moderate to severe RA
- can be in combination with MTX
TNFα-Blocker examples
- adalimumab (40 mg sc)
- infliximab (3 mg/kg iv at 2, 6 then 8 weeks)
- etanercept (25 mg sc twice weekly)
Rituximab
- monoclonal antibody against CD20 on B-cells (removes them)
- high risk of allergy –> give pre-medication (ex: steroid, antihistamine) before each infusion)
Sarilumab
monoclonal antibody against IL-6 receptor
inadequate response / intolerance to 1 or more DMARDs
Abatacept
-prevent binding B7 protein and CD28 –> activation of T cells
not cost-effective –> not recommended by NICE
Anakinra
Interleukin-1 inhibitors
low efficacy–> rejected by NICE
Tofacitinib
Janus Kinase inhibitor
Janus kinase involved in cytokine signalling and gene transcription
rejected by NICE unless company reduce price
