Pharmacology of Arthritis

Question 1

What is the first step of arthritis treatment?

Answer 1

Non-opioid (e.g aspirin, paracetamol, NSAID) +/- adjuvant

Question 2

What is the second step of arthritis treatment?

Answer 2

Weak opioid for mild to moderate pain (e.g codeine) +/- non-opioid +/- adjuvant

Question 3

What is the third step of arthritis treatment?

Answer 3

Strong opioid for moderate to severe pain (e.g morphine) +/- non-opioid +/- adjuvant

Question 4

What does NSAID stand for?

Answer 4

Non-steroidal anti-inflammatory

Question 5

What properties do NSAIDs have?

Answer 5

Anti-inflammatory and analgesic

Question 6

What are some examples of NSAIDs?

Answer 6

Ibuprofen, naproxen, diclofenac, indometacin, etodolac, celecoxib

Question 7

What are some indications for NSAID use?

Answer 7

Inflammatory arthritis, mechanical MSK pain, pleuritic/pericardial pain

Question 8

What are some adverse effects of NSAIDs?

Answer 8

Dyspepsia, oesophagitis, gastritis, peptic ulcer, small/large bowel ulceration, renal impairment, increased CV events, fluid retention, wheeze, rash

Question 9

What does DMARD stand for?

Answer 9

Disease-modifying anti-rheumatic drugs

Question 10

How should DMARDs be used to treat inflammatory arthritis?

Answer 10

Early aggressive DMARD therapy, start treatment within 3 months of symptom onset

Question 11

What are some features of DMARDs?

Answer 11

Slow acting (weeks-months), pure anti-inflammatory action with no analgesic effect, reduce rate of joint damage, most need regular monitoring for side effects

Question 12

What are some examples of DMARDs?

Answer 12

Methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, penicillamine, sodium aurothiomalate (gold)

Question 13

What are some features of methotrexate?

Answer 13

Mode of action unknown, folate antagonist, 1st choice DMARD in many patients, given orally or subcutaneously, often used in combination

Question 14

What are some indications for methotrexate use?

Answer 14

Rheumatoid arthritis, psoriatic arthritis, connective tissue disease, vasculitis

Question 15

What needs to be monitored in patients on methotrexate and sulfasalazine?

Answer 15

FBC and LFTs

Question 16

What are some adverse effects of methotrexate?

Answer 16

Leucopenia/thrombocytopenia, hepatitis/cirrhosis (must limit alcohol intake), pneumonitis, rash, mouth ulcers, nausea, diarrhoea

Question 17

What are some teratogenic DMARDs?

Answer 17

Methotrexate and leflunomide = must be stopped at least three months before conception in male and females

Question 18

What are some features of leflunomide?

Answer 18

Similar efficacy and side effects to methotrexate, very long half life so requires wash out

Question 19

What is sulfasalazine used to treat?

Answer 19

Often used in combination with methotrexate to treat inflammatory arthritis

Question 20

What are some adverse effects of sulfasalazine?

Answer 20

Nausea, rash, mouth ulcers, neutropenia, hepatitis, reversible oligozoospermia

Question 21

What are some features of hydroxychloroquine?

Answer 21

No effect on joint damage, can cause retinopathy

Question 22

What is hydroxychloroquine used to treat?

Answer 22

Used in connective tissue diseases = SLE (helps skin, joints and with general malaise), Sjogren’s syndrome, rheumatoid arthritis

Question 23

What are some features of penicillamine?

Answer 23

Oral, has same adverse effects as IM sodium aurothiomalate (gold)

Question 24

How is sodium aurothiomalate (gold) given?

Answer 24

Intramuscularly (IM)

Question 25

What are some adverse effects of sodium aurothiomalate (gold)?

Answer 25

Bone marrow suppression, glomerulonephritis, rash, mouth ulcers (monitor FBC plus urine for proteinuria)

Question 26

What are biologics?

Answer 26

Drugs designed to target specific aspects of immune system found to be impacted in inflammatory arthritis (e.g anti-TNF drugs)

Question 27

What is anti-TNF therapy licenced to treat?

Answer 27

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

Question 28

How effective is anti-TNF therapy?

Answer 28

About 1.5 times as effective as standard DMARDs, more effective in combination with DMARDs

Question 29

How are most anti-TNF agents delivered?

Answer 29

By subcutaneous injection

Question 30

What are some examples of anti-TNF agents?

Answer 30

Etanercept, adalimumab, certolizumab, infliximab, golimumab

Question 31

What is an example of a biosimilar to anti-TNF agents?

Answer 31

Benepali

Question 32

What are the criteria for prescribing anti-TNF therapy?

Answer 32

High disease activity score, use of previous standard DMARDs

Question 33

What are the adverse effects of anti-TNF agents?

Answer 33

Risk of infection (especially TB), possible risk of cancer (especially skin)

Question 34

When are anti-TNF agents contra-indicated?

Answer 34

In patients with pulmonary fibrosis or heart failure

Question 35

What are some other biologic agents?

Answer 35

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

Question 36

What agents are used to treat acute gout?

Answer 36

Colchicine (causes diarrhoea), NSAIDs, steroids (oral, IM)

Question 37

What are some agents used in the prophylactic treatment of gout?

Answer 37

Allopurinol, febuxostat, uricosurics

Question 38

What is allopurinol and what are some of its adverse effects?

Answer 38

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

Question 39

What is febuxostat and what are some of its side effects?

Answer 39

Xanthine oxidase inhibitor prescribed for patients who can't tolerate allopurinol; renal impairment, use cautiously in patients with ischaemic heart disease

Question 40

What are some examples of uricosurics?

Answer 40

Probenecid, sulphinpyrazone, azapropazone, benzbromarone

Question 41

When are corticosteroids indicated?

Answer 41

Connective tissue diseases, polymyalgia rheumatica/giant cell arteritis, vasculitis, rheumatoid arthritis

Question 42

How can corticosteroids be administered?

Answer 42

Oral, intra-articular, soft tissue injection, IV, IM

Question 43

What are some side effects of corticosteroids?

Answer 43

Weight gain (centripetal obesity), muscle wasting, skin atrophy, osteoporosis, diabetes, hypertension, cataract, glaucoma, fluid retention, adrenal suppression, immunosuppression, avascular necrosis of femoral head

Question 44

How can corticosteroid toxicity be reduced?

Answer 44

Use lowest possible dose for as short a time as possible Consider steroid-sparing agents Osteoporosis prophylaxis Watch CV risk factors

Question 45

What are the considerations that must be made for patients on drugs that may impact conception?

Answer 45

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