MSK Pharmacology Flashcards
Two methods of managing inflammatory arthritis?
Symptom relief: Paracetamol Opiate compounds NSAIDs Atypical analgesics
Disease modifiers:
DMARDs - methotrexate, sulphasalazine, hydroxychloroquine
Biologics - anti-TNF (rituximab, tocilizumab)
What are pure analgesics?
E.g: paracetamol (pure analgesic with little anti-inflammatory action); it is a component of many compound analgesics, like co-codamol
Adverse effects are rare in therapeutic doses but they are very dangerous in overdose
Types of analgesics?
Co-codamol
Dihydrocodeine
Tramadol
Add-on drugs:
Amitriptyline
Gabapentin
Steps in pain treatment ladder?
Step 1:
Non-opioid (e.g: aspirin, paracetamol, NSAID) +/- adjuvant
Step 2:
Weak opioid for mild to moderate pain, e.g: codeine, +/- non-opioid +/e adjuvant
Step 3:
Strong opioid for moderate to severe pain, e.g: morphine, +/- non-opioid +/- adjuvant
Examples of NSAIDs?
Ibuprofen Naproxen (first in Tayside) Diclofenac Indometacin Etodolac Celecoxib (cox-2 inhibitor)
Indications for NSAID use?
Inflammatory arthritis
Mechanical MSK pain
Pleuritic/pericardial chest pain
Other painful conditions
Adverse effects of NSAIDs?
Dyspepsia
Oeosphagitis and gastritis
Peptic and small/large bowel ulceration
Renal impairment
Increased risk of CV events (esp. with cox-2 inhibitors)
Fluid retention
Wheeze
Rash
What are Cox-2 inhibitors?
NSAIDs which selectively target cyclooxygenase-2, an enzyme responsible for inflammation and pain
Targeting COX-2 selectively reduces the risk of peptic ulceration
Action of DMARDs?
Purely anti-inflammatory with no direct analgesic effect; they reduce the rate of joint damage but are SLOW-ACTING (takes weeks to months)
Indications for DMARDs?
Active inflammatory disease where the benefit > risk (usually always)
Almost all patient will new onset RA; aim to start a DMARD within 3 months of symptoms onset
Commonly used DMARDs?
Methotrexate (1st line)
Sulphasalazine
Leflunomide
Hydroxychloroquine
Steps in DMARD therapy for RA, according to SIGN guideliness?
- Methotrexate and sulphasalazine are DMARDs of choice
- Therapy should be sustained in patient with early RA to control symptoms and signs
- Combination DMARD strategy, rather than monotherapy, if patients have an inadequate response, i.e: add another DMARD to the initial
Steroids and NSAIDs are used as bridging therapy, until the DMARD provides relief
How is methotrexate used in RA?
Unknown mode of action
1st CHOICE DMARD and can be given orally/subcutaneously; it is often used in combination with another DMARD
It is a folate antagonist, so folic acid supplementation
Conditions in which methotrexate is used?
RA, psoriatic arthritic, CTD and vasculitis
Adverse effects of methotrexate?
Leucopenia/thrombocytopenia
Hepatitis/cirrhosis (alcohol intake must be limited)
Pneumonitis
Rash/mouth ulcers
Nausea/diarrhoea
Teratogenic (must be stopped in males and females at least 3 months before conception)
Monitoring with methotrexate use?
FBC and LFTs regularly
Use of sulphasalazine?
Often used in combo with methotrexate in early inflammatory arthritis
Adverse effects of sulphasalazine?
Nausea
Severe rash and mouth ulcers
Neutropenia
Hepatitis
Reversible oligozoospermia (semen with a low conc. of sperm)
Monitoring sulphasalazine use?
FBC and LFTs
Use of leflunomide?
Similar efficacy to methotrexate and similar side effects (also teratogenic)
It has a very long half-life so patients must not become pregnancy for 2 years after stopping
It can be a 2nd line drug, in compe with sulphasalazine, for RA if, e.g: the patient cannot tolerate methotrexate
Use of hydroxychloroquine in RA?
NO EFFECT on joint damage but used in connective tissue disease, such as SLE, Sjogren’s syndrome and RA (as an add-on therapy)
Adverse effects of hydroxychloroquine?
Rarely, retinopathy
What are biologics?
Target specific components of the immune system that are implicated in inflammatory arthritis, e.g: TNF, IL-6, etc
Use of biologics?
Currently licensed for RA, psoriatic arthritis and ankylosing spondylitis
More effective in combo with DMARDs and are mostly administered via sub-cutaneous injection
Examples of anti-TNF drugs?
Etanercept, Adalimumab, Certolizumab, Infliximab, Golimumab
Biosimilars: Benepali
Conditions to be met before qualifying for biologic prescription?
High DAS 28 score (> 5.1)
Must have tried 2 DMARDs, inc. methotrexate
Adverse effects of anti-TNF drugs?
Risk of infection
REACTIVATION OF LATENT TB (if a patient comes with fever, night sweats, weight loss, etc, be suspicious of this)
Slightly increased risk of skin cancer
Contraindicated in pulmonary fibrosis and heart failure
Other biologic agents?
Rituximab (B-cell depletor)
Tocilizumab (inhibits IL-6), Ustekinumab (inhibitts IL-12 and 23), Secukinimab (inhibits IL-12 and 23)
Abatacept (blocks full activation of T cells)
Summary of the biologics used in different MSK disorders?
PICTURE 10
Treatment of an acute episode of gout?
- NSAIDs + PPI
- If NSAIDs are contraindicated, Colchicine (commonly causes diarrhoea)
- If both of the above are contraindicated, steroids (oral/IM)
These suppress pain and inflammation until the acute flare ends
Also, advise an ice pack
Testing in an acute flare of gout?
Serum uric acid (may be low during an acute flare, as uric acid precipitates)
Drugs used for gout prophylaxis?
Started a few weeks after an acute flare, as it can sometimes worse a flare
- Allopurinol
- If contraindicated, febuxostat
- Uricosurics, e.g: probenecid, azapropazone
How do urate-lowering drugs, like allopurinol/febuxostat, work?
Xanthine oxdiase (converts xanthine to uric acid) inhibitors
Adverse effects of allopurinol?
Rash (vasculitis) commoner in elderly and in renal impairment, therefore use lower doses
Rarely, irreversible bone marrow aplasia
Contraindications with allopurinol?
Azathioprine interaction can cause irreversible bone marrow aplasia
Adverse effects of febuxostat?
Renal impairment
Use in caution in patients with ischaemic heart disease
How to decide if gout prophylaxis is required?
Follow-up 6 weeks later and measure serum uric acid
If above 360 micromoles/L, or if they have had previous episodes, prescribe
Aim of gout prophylaxis?
Uric acid < 360 micromoles/L makes it very unlikely that they will have any more episodes
Indications for steroid use?
CTDs, polymyalgia rheumatica/giant cell arteritis, vasculitis, RA
Adverse effects of corticosteroids?
Centripetal obesity
Muscle wasting
Skin atrophy
Osteoporosis (lower bone density)
Diabetes
Hypertension
Cataract and glaucoma
Adrenal suppression
Immunosuppression
Avascular necrosis of the femoral head
How are steroids used for these conditions?
Tend to be given as short, low doses but there are exceptions; consider steroid-sparing agents and osteoporosis prophylaxis
Monitor CV risk factors
