Pharmacology of Arthritis Flashcards
What is the first step of arthritis treatment?
Non-opioid (e.g aspirin, paracetamol, NSAID) +/- adjuvant
What is the second step of arthritis treatment?
Weak opioid for mild to moderate pain (e.g codeine) +/- non-opioid +/- adjuvant
What is the third step of arthritis treatment?
Strong opioid for moderate to severe pain (e.g morphine) +/- non-opioid +/- adjuvant
What does NSAID stand for?
Non-steroidal anti-inflammatory
What properties do NSAIDs have?
Anti-inflammatory and analgesic
What are some examples of NSAIDs?
Ibuprofen, naproxen, diclofenac, indometacin, etodolac, celecoxib
What are some indications for NSAID use?
Inflammatory arthritis, mechanical MSK pain, pleuritic/pericardial pain
What are some adverse effects of NSAIDs?
Dyspepsia, oesophagitis, gastritis, peptic ulcer, small/large bowel ulceration, renal impairment, increased CV events, fluid retention, wheeze, rash
What does DMARD stand for?
Disease-modifying anti-rheumatic drugs
How should DMARDs be used to treat inflammatory arthritis?
Early aggressive DMARD therapy, start treatment within 3 months of symptom onset
What are some features of DMARDs?
Slow acting (weeks-months), pure anti-inflammatory action with no analgesic effect, reduce rate of joint damage, most need regular monitoring for side effects
What are some examples of DMARDs?
Methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, penicillamine, sodium aurothiomalate (gold)
What are some features of methotrexate?
Mode of action unknown, folate antagonist, 1st choice DMARD in many patients, given orally or subcutaneously, often used in combination
What are some indications for methotrexate use?
Rheumatoid arthritis, psoriatic arthritis, connective tissue disease, vasculitis
What needs to be monitored in patients on methotrexate and sulfasalazine?
FBC and LFTs
What are some adverse effects of methotrexate?
Leucopenia/thrombocytopenia, hepatitis/cirrhosis (must limit alcohol intake), pneumonitis, rash, mouth ulcers, nausea, diarrhoea
What are some teratogenic DMARDs?
Methotrexate and leflunomide = must be stopped at least three months before conception in male and females
What are some features of leflunomide?
Similar efficacy and side effects to methotrexate, very long half life so requires wash out
What is sulfasalazine used to treat?
Often used in combination with methotrexate to treat inflammatory arthritis
What are some adverse effects of sulfasalazine?
Nausea, rash, mouth ulcers, neutropenia, hepatitis, reversible oligozoospermia
What are some features of hydroxychloroquine?
No effect on joint damage, can cause retinopathy
What is hydroxychloroquine used to treat?
Used in connective tissue diseases = SLE (helps skin, joints and with general malaise), Sjogren’s syndrome, rheumatoid arthritis
What are some features of penicillamine?
Oral, has same adverse effects as IM sodium aurothiomalate (gold)
How is sodium aurothiomalate (gold) given?
Intramuscularly (IM)
What are some adverse effects of sodium aurothiomalate (gold)?
Bone marrow suppression, glomerulonephritis, rash, mouth ulcers (monitor FBC plus urine for proteinuria)
What are biologics?
Drugs designed to target specific aspects of immune system found to be impacted in inflammatory arthritis (e.g anti-TNF drugs)
What is anti-TNF therapy licenced to treat?
Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis
How effective is anti-TNF therapy?
About 1.5 times as effective as standard DMARDs, more effective in combination with DMARDs
How are most anti-TNF agents delivered?
By subcutaneous injection
What are some examples of anti-TNF agents?
Etanercept, adalimumab, certolizumab, infliximab, golimumab
What is an example of a biosimilar to anti-TNF agents?
Benepali
What are the criteria for prescribing anti-TNF therapy?
High disease activity score, use of previous standard DMARDs
What are the adverse effects of anti-TNF agents?
Risk of infection (especially TB), possible risk of cancer (especially skin)
When are anti-TNF agents contra-indicated?
In patients with pulmonary fibrosis or heart failure
What are some other biologic agents?
Rituximab = monoclonal antibody against B (CD20) lymphocytes
Tocilizumab = inhibits IL-6
Abatacept = CTLA-4 Ig blocks full activation of T cells
Ustekimimab = inhibits IL-12 and IL-23
Secukinimab = inhibits IL-17
Tofacitinib and Baricitinib = janus kinase inhibitors
What agents are used to treat acute gout?
Colchicine (causes diarrhoea), NSAIDs, steroids (oral, IM)
What are some agents used in the prophylactic treatment of gout?
Allopurinol, febuxostat, uricosurics
What is allopurinol and what are some of its adverse effects?
Xanthine oxidase inhibitor; rapid reduction in uric acid may exacerbate gout, rash (vasculitis) more common in elderly and renal impairment, azathioprine interaction, rarely marrow aplasia
What is febuxostat and what are some of its side effects?
Xanthine oxidase inhibitor prescribed for patients who can’t tolerate allopurinol; renal impairment, use cautiously in patients with ischaemic heart disease
What are some examples of uricosurics?
Probenecid, sulphinpyrazone, azapropazone, benzbromarone
When are corticosteroids indicated?
Connective tissue diseases, polymyalgia rheumatica/giant cell arteritis, vasculitis, rheumatoid arthritis
How can corticosteroids be administered?
Oral, intra-articular, soft tissue injection, IV, IM
What are some side effects of corticosteroids?
Weight gain (centripetal obesity), muscle wasting, skin atrophy, osteoporosis, diabetes, hypertension, cataract, glaucoma, fluid retention, adrenal suppression, immunosuppression, avascular necrosis of femoral head
How can corticosteroid toxicity be reduced?
Use lowest possible dose for as short a time as possible
Consider steroid-sparing agents
Osteoporosis prophylaxis
Watch CV risk factors
What are the considerations that must be made for patients on drugs that may impact conception?
Some drugs may alter fertility and others can have an effect on foetal development (e.g methotrexate), important to discuss implications with patients before starting treatment and when planning a family
