Overview of drug treatments of RA

Question 1

What are the 3 therapeutic targets of drugs for inflammatory arthritis?

Answer 1

Relieve symptoms

Avoid permanent joint damage

Reduce systemic complications of chronic inflammation

Question 2

Give 4 symptoms of inflammatory arthritis?

Answer 2

Pain, swelling, fatigue, EMS

Question 3

Give 2 systemic complications of chronic inflammation?

Answer 3

Anemia: lack of healthy RBCs

Amyloidosis: excess antibody buildup in form of amyloid (protein)

Question 4

Why should physiotherapy be considered for systemic pain relief of RA?

Answer 4

Best to stay as active as possible, especially if there is severe joint damage

Question 5

Why should occupational therapy be considered for systemic pain relief of RA?

Answer 5

Modifications can help when patient suffers from EMS, severe joint damage

Question 6

What are the 2 main medications used when there is localised joint problems caused by RA?

Answer 6

NSAIDs, paracetamol

Question 7

Give 3 organs that can suffer from harmful long-term side effects of NSAIDs?

Answer 7

Heart, kidney, GI tract

Question 8

When can a local corticosteroid injection be administered for RA?

Answer 8

For one large joint only

Question 9

Is local corticosteroid injection suitable for repeated use?

Answer 9

No, as this can cause toxicity

Question 10

When is surgery appropriate for localised joint problems due to RA?

Answer 10

Very severe joint damage to extent that joint replacement is needed

Question 11

What is the therapeutic effect of NSAIDs?

Answer 11

Decreases prostaglandin E2 and prostacylins

Question 12

What is the analgesic effect of NSAIDs?

Answer 12

Decrease of prostaglandins makes nerves less sensitive to inflammatory mediators

Question 13

What is the anti-pyretic effect of NSAIDs?

Answer 13

Decrease of IL-1

Question 14

Why are NSAIDs described as imprecise targets?

Answer 14

They block COX enzymes which reduces too many prostaglandins, so causes ‘off-target’ bystander damage (side effects) as well as ‘on-target’ pain relief

Question 15

How is decreased clotting a side effect of NSAIDs?

Answer 15

Platelet activity is decreased

Question 16

How are peptic ulcers a side effect of NSAIDs?

Answer 16

Peptic ulcers form due to direct erosion of stomach lining and less protective mucus is produced due to decreased prostaglandins

Question 17

How long does it take for local corticosteroids to start therapeutic effects after injection?

Answer 17

Few days

Question 18

What is the condition caused as a side effect of long-term use of corticosteroids?

Answer 18

Osteoporosis

Question 19

What are DMARDs?

Answer 19

Disease Modifying Anti Rheumatic Drugs

Question 20

What is the main therapeutic effect of DMARDs?

Answer 20

Immunosuppressant drugs that suppress inflammation to prevent permanent joint damage and cartilage erosion

Question 21

Why is bridging therapy used for DMARDs?

Answer 21

Bridging therapy provides rapid, effective inflammation suppression whilst waiting for administered DMARDs to take effect

Question 22

Give one example of a bridging therapy used for DMARDs?

Answer 22

Corticosteroids

Question 23

What DMARD are patients usually started on until RA progresses?

Answer 23

Methotrexate with steroids

Question 24

Why is methotrexate the first-line drug for RA?

Answer 24

Very good efficacy and is the most established DMARD

Question 25

What 4 factors are can be affected by methotrexate when considering drug safety?

Answer 25

Increased infection susceptibility Liver toxicity Folic acid antagonist Lung damage

Question 26

What bridging therapy is used for methotrexate?

Answer 26

Folic acid

Question 27

When are folic acid and methotrexate administered?

Answer 27

Different days

Question 28

Does the patient need to be monitored regularly when they are taking methotrexate?

Answer 28

Yes, need to regularly do full blood count, test renal and liver function

Question 29

What makes patients suitable to take methotrexate?

Answer 29

No susceptibility/current/past liver or renal problems

Question 30

What drug does methotrexate interact with?

Answer 30

Trimethoprim

Question 31

Why can't methotrexate be used with trimethoprim?

Answer 31

They both act on folic acid pathway and cause folate deficiency

Question 32

How can trimethoprim and methotrexate affect bone marrow when they are used at the same time?

Answer 32

Folate deficiency anaemia: Folate deficiency causes bone marrow to produce abnormally large RBCs, which are too big to enter bloodstream and those that do enter aren't healthy

Question 33

What are the usual starting doses for methotrexate and folic acid, and when should they be administered?

Answer 33

Methotrexate: 7.5 mg on monday orally/subcutaneous injection Folic acid: 5 mg on friday

Question 34

If the starting dose of methotrexate doesn't provide adequate health benefits, how can the dosage be adjusted?

Answer 34

Titrate up to 20 mg over months

Question 35

What is the guideline for when to start use of TNF-alpha blocker agents?

Answer 35

At least 2 DMARDs (including methotrexate) were tried and ineffective for more than 6 months

Question 36

What drug is TNF-alpha inhibitor usually administered with for active RA?

Answer 36

Methotrexate

Question 37

How efficacious are TNF-alpha blocker agents?

Answer 37

Very good efficacy

Question 38

What 2 effects of TNF-alpha blocker agents should be considered in terms of safety?

Answer 38

Causes immunosuppression, reaction to injections

Question 39

What patients are suitable to take TNF-alpha blocker agents?

Answer 39

Patients who don't have reactions to injections or infusions It is also an expensive treatment

Question 40

What is the mechanism of infliximab?

Answer 40

Human-mouse monoclonal antibody that targets TNF-alpha, inhibiting inflammation

Question 41

Other than RA, what can infliximab be used to treat?

Answer 41

Psoriatic arthritis

Question 42

What is etanercept, and what is its mechanism of action?

Answer 42

Recombinant human TNF-alpha p75 Fc region fusion protein (produced from recombinant DNA) Binds to TNF-alpha and inhibits it

Question 43

What 3 conditions can etanercept be used to treat, other than RA?

Answer 43

Ankylosing spondylitis Juvenile idiopathic arthritis Psoriatic arthritis

Question 44

What is the mechanism of action of adalimumab?

Answer 44

Human monoclonal antibody that binds to TNF-alpha

Question 45

What 2 conditions are treated with adalimumab, other than RA?

Answer 45

Ankylosing spondylitis Psoriatic arthritis

Question 46

What type of drugs are used if TNF-alpha blocker agents fail?

Answer 46

Drugs that have other targets

Question 47

Give 5 examples of drugs used to treat RA after TNF-alpha blocker agents fail?

Answer 47

rituximab: acts on CD20 tocilizumab: acts on IL-6 golimumab belimumab: inhibits B-cell activating factor Janus Kinase (JAK) inhibitors: tofacitinib, baricitinib

Question 48

What does rituximab act on to treat RA?

Answer 48

CD20

Question 49

What does tocilizumab act on to treat RA?

Answer 49

IL-6

Question 50

What 2 drugs do patients usually try before taking belimumab?

Answer 50

Hydroquinone, corticosteroids

Question 51

What other condition is belimumab used to treat, other than RA?

Answer 51

SLE

Question 52

Give 2 examples of JAK inhibitors that are used to treat RA?

Answer 52

Tofacitinib, baricitinib

Question 53

Why are JAK inhibitors more convenient than other biologics in terms of administration?

Answer 53

Most biologics are administered by IV or IM, but JAK inhibitors can be given orally

Question 54

Why are corticosteroids very good and efficacious immunosuppressants?

Answer 54

They have multiple target sites

Question 55

How does Cushing's disease occur?

Answer 55

Cortisol excess due to very slow tapering/withdrawal of corticosteroids

Question 56

What are the symptoms of Cushing's disease?

Answer 56

Osteoporosis, obesity, moon face, buffalo hump, hypertension, hyperglycemia, striae, myopathy, psychiatric, hypokalemia

Question 57

What is the buffalo hump, seen in Cushing's disease?

Answer 57

Excess fat buildup behind neck, which is the dorsal cervical fat pad

Question 58

What is the moon face, seen in Cushing's disease?

Answer 58

Extra fat buildup on sides of face so that face looks round

Question 59

In Cushing's disease, where does obesity typically present in the body?

Answer 59

Truncal obesity (concentrated in center of body rather than extremities)

Question 60

How does Addison's disease occur?

Answer 60

Cortisol deficiency due to very fast tapering/withdrawal of corticosteroids

Question 61

What are the symptoms of Addison's disease?

Answer 61

Nausea, vomiting, headache, joint pain, fever, hypoglycemia, hypotension, hyperkalemia

Question 62

Which 2 corticosteroids are injected into a single painful joint?

Answer 62

Triamcinolone, methylprednisolone

Question 63

Which corticosteroid is given orally in acute flare ups, and what is the dosage and duration?

Answer 63

30mg prednisolone given orally daily for 2 weeks

Question 64

What 2 corticosteroids are given in severe flare ups, and what is the route of administration?

Answer 64

Hydrocortisone, methylprednisolone given intravenously

Question 65

Can corticosteroids be administered as topical formulations?

Answer 65

Yes, different formulations have different strengths