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CPT Summaries > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

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1
Q

What effect have DMARDs been shown to have in RA?

A

Slow course of disease
Induce remission
Prevent further destruction of joints and involved tissues

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2
Q

What treatment should be given when a patient is diagnosed with RA?

A

Initiation of DMARDs within 3 months, in addition to NSAIDs, low-dose corticosteroids, physical therapy, and occupational therapy

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3
Q

Why is therapy with DMARDs initiated rapidly in RA?

A

To stop the progression of the disease at earlier stage

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4
Q

Is methotrexate used alone or in combination therapy in rheumatoid arthritis?

A

Either

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5
Q

What kind of arthritis is methotrexate the mainstay treatment in?

A

Rheumatoid or psoriatic

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6
Q

What is the effect of methotrexate on the radiograph?

A

It slows the appearance of new erosions with involved joints

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7
Q

When does response to methotrexate occur?

A

Within 3 to 6 months of starting treatment

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8
Q

What kind of drug is methotrexate?

A

Immunosuppressant

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9
Q

What can be done when there is a partial or no response to methotrexate?

A

Other DMARDs can be added

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10
Q

How are the adverse effects of methotrexate minimised?

A

The doses required for treatment are much lower, and given once a week

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11
Q

What are the most common side effects of methotrexate therapy in the treatment of RA?

A

Mucosal ulceration and nausea

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12
Q

What side effects might be seen with chronic administration of methotrexate in RA?

A

Cytopenias, particularly depression of WBC count, cirrhosis of the liver, and acute pneumonia-like syndrome

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13
Q

What monitoring is required with methotrexate?

A

Signs of infection
Complete blood count
Liver enzyme tests

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14
Q

What are the serious side effects of methotrexate?

A 
Mucositis 
Bone marrow suppression
Hepatitis
Cirrhosis
Infection risk
Teratogenic abortifactant
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15
Q

What is the oral bioavailability of methotrexate?

A

Very variable dependant on dose, but when given IV, about 50%

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16
Q

What is the half life of methotrexate?

A

Dependant on dose, but in high doses, about 8-10 hours

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17
Q

How is methotrexate metabolised?

A

Undergoes intracellular/hepatic metabolism to polyglutamates

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18
Q

How is methotrexate eliminated?

A

90% renal, through glomerular active and tubular secretion

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19
Q

What therapeutic DDIs does methotrexate have?

A

Other immunosuppressants, anti-cancer drugs, and in auto-immune conditions

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20
Q

What adverse DDIs does methotrexate have?

A

Drugs affecting renal blood flow, renal elimination, and drugs affecting plasma protein binding, phenytoin, tetracyclines, pencillin.
In combination with these, increased risk of myelosupression

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21
Q

What is sulfasalazine made up of?

A

5-aminosalicylate and sulfapyridine

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22
Q

Describe the absorption of sulfasalazine

A

It has unique pharmacokinetics in the gut, and travels through the length of the upper GI tract until it reaches the colon. Then, in the colon, bacterialaction causes the breakdown of sulfasalazine into 5-ASA and sulfapyridine.

23
Q

What is the mechanism of action of sulfasalazine in RA?

A

Unclear, not to do with COX-2 inhibition.
Appears to inhibit T-cell proliferation and IL-2 production, and may cause T-cell apoptosis. In neutrophils, it reduces chemotaxis and degranulation

24
Q

What component of sulfasalazine causes ADRs?

A

Sulfapyridine

25
Q

What % of patients on sulfapyridine (sulfasalazine) experience ADRs?

A

10-45%

26
Q

What are the common ADRs of sulfapyridine (sulfasalazine)?

A

Nausea, fatigue, headache

27
Q

What are the serious ADRs of sulfapyridine (sulfasalazine)?

A

Myelosuppression, hepatitis, allergic rash

28
Q

Is sulfasalazine safe in pregnancy?

A

Yes

29
Q

What are the DDIs with sulfasalazine

A

Few

30
Q

What is the onset of action of sulfasalazine treatment in RA?

A

1-3 months

31
Q

What are IL-1 and TNF-alpha?

A

Pro-inflammatory cytokines involved in the pathogenesis of RA

32
Q

What secretes IL-1 and TNF-alpha?

A

Synovial macrophages

33
Q

What happens when synovial macrophages secrete IL-1 and TNF-alpha?

A

It stimulates synovial cells to proliferate and synthesise collagenase, thereby degrading cartilage, stimulating bone reabsorption, and inhibiting proteoglycan synthesis

34
Q

What effect do TNF-alpha inhibitors have on RA?

A

Shown to decrease signs and symptoms of RA, reduce progression of structural damage, and improve physical function

35
Q

What is the onset of response with TNF-alpha inhibitors in RA?

A

Within 2 weeks

36
Q

What are patients receiving TNF-alpha inhibitors at increased risk of?

A

Tuberculosis, sepsis, fungal opportunistic infections, pancytopenia

37
Q

What rare but serious ADRs can occur with TNF-alpha inhibitors?

A

Demyelinating disorders and bone marrow suppression

38
Q

What conditions should TNF-alpha inhibitors be caused cautiously with?

A

Heart failure

39
Q

Why should TNF-alpha inhibitors be caused cautiously with heart failure?

A

Because they can cause or worsen pre-existing heart failure

40
Q

Give 3 examples of TNF-alpha inhibitors

A

Infliximab, adalimumab, rituximab

41
Q

What is the mechanism of action of infliximab?

A

It is a monoclonal antibody that binds specifically to human TNF-alpha, and inhibits binding with its receptors

42
Q

Where is infliximab approved for use?

A

Patients with RA who have had inadequate response to methotrexate monotherapy

43
Q

How is infliximab administered?

A

It is infused IV over at least 2 hours

44
Q

What is the half life of infliximab?

A

9.5 days

45
Q

What are the adverse effects of infliximab

A

Infusion site reactions, e.g. fever, chills, pruritus, and utricaria
Infections leading to pneumonia, cellulitis, and other conditions
Leukopenia, neutropenia, thrombocytopenia, and pancytopenia

46
Q

What is the mechanism of action of adalimumab?

A

A recombinant monoclonal antibody that binds to TNF-alpha, thereby interfering with endogenous TNF-alpha activity by blocking its binding to surface receptors

47
Q

What are the indications for adalimumab?

A

Severe RA, either as monotherapy or in combination with methotrexate

48
Q

How is adalimumab administered?

A

Subcutaneously weekly, or every other week

49
Q

What are the adverse effects of adalimumab?

A

Headache, nausea, agranulocytosis, rash, reaction at injection site, increased risk of infection

50
Q

What is the role of B lymphocytes in RA?

A

B lymphocytes can perpetuate the inflammatory process in the synvoium by activating T lymphocytes, producing autoantibodies, and producing pro-inflammatory cytokines such as TNF-alpha and IL-1

51
Q

What is the mechanism of action of rituximab in RA?

A

It is a monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes, resulting in B-cell depletion

52
Q

What is the indication for use of rituximab?

A

In combination with methotrexate, to reduce signs and symptoms of severe RA in adult patients who have inadequate response to one or more TNF-inhibitors

53
Q

How is rituximab adminstered?

A

2 IV infusions separated by 2 weeks

54
Q

What are the adverse effects of rituximab?

A

Infusion reactions are most common

CPT Summaries (8 decks)

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