NSAIDs 2 - Rheumatoid arthritis Flashcards

1
Q

What population is mostly affected by Rheumatoid arthritis? What part of the body is usually affected?

A

It’s more common in women (3x)
Commonly affects small joints of the hand, wrists, and feet
Ankles, elbows, hips, knees, and shoulders may also be affected

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2
Q

What causes rheumatoid arthritis?

A

It’s an autoimmune response caused by activated T and B cells and activation of polymorphonuclear leukocytes
This leads to the release of inflammatory cytokines which leads to joint inflammation and destruction

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3
Q

What are DMARDs?

A

Disease-modifying antirheumatoid drugs

These are agents given to slow or halt damage and scarring with chronic inflammatory disease

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4
Q

How do DMARDs work?

A

They work by suppressing neutrophils, macrophages, and they act as immunosuppressants.

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5
Q

When do we use DMARDs?

A

After previous NSAIDs have been tried and they failed

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6
Q

Do DMARDs work right away?

A

No there is a latency period for effectiveness

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7
Q

Mechanism of action of gold salts?

A

Inhibits migration of macrophages into the synovial fluid
Inhibits phagocytic actions of macrophages
Inhibits cytotoxic effects of T-cells
Suppresses maturation and function of macrophages and T-cells

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8
Q

How long do gold salts take to work?

A

3-6 months

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9
Q

Adverse effects of gold salts?

A

Accumulation in skin and mucous membranes (15%)
Can cause rashes, skin discoloration (blue-grey)
Lesions of mucous membranes (mouth, GI, vaginitis)
Tubule damage in kidneys (5-10%)
Hematological problems (1-10%) - thrombocytopenia, aplastic anemia

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10
Q

How are gold salts administered?

A

Auranofin (oral)

Aurothioglucose/Gold sodium thiomalate (IM)

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11
Q

Are gold salts well tolerated?

A

15-35% discontinue therapy due to side effects

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12
Q

When do we use gold salts?

A

Always used AFTER NSAIDs have been tried, their use is limited

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13
Q

How do corticosteroids work in RA?

A

Pharmacological doses used to suppress immune system

They inhibit the formation of cytokines, including interleukins, TNF

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14
Q

When do we use corticosteroids?

A

Short term use usually (limited long term use)

Used for flair ups

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15
Q

How does methotrexate work in RA?

A

It decreases folic acid synthesis to inhibit DNA synthesis, which inhibits lymphocyte proliferation

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16
Q

How is methotrexate administered for RA?

A

Low doses
Oral or parenteral, once weekly
Takes 2-3 weeks to see effect

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17
Q

How long can pts be on methotrexate? Corticosteroids?

A

Short term corticosteroids

Methotrexate pts have been on for 5-7 years and it’s still working soo

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18
Q

Toxicities associated with methotrexate?

A

Nausea
Mucosal ulcers
Hepatotoxicity

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19
Q

When do we use Leucovorin?

A

As a MTX rescue

Use it 24 hours after methotrexate administration to rescue normal cells

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20
Q

What is Leflunamide?

A

Inhibitor of mononuclear and T cell proliferation

Inhibits immune cell DNA synthesis

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21
Q

When do we use Leflunamide?

A

It’s used as an alternative to methotrexate

22
Q

Cautions with Leflunamide?

A

Hepatotoxicity
Bone marrow suppression
Absolutely contraindicated in pregnancy (Teratogenic)

Other side effects: Diarrhea, alopecia

23
Q

How does Chlorambucil work?

A

It’s a nitrogen mustard, used to decrease DNA synthesis/formation of immune cells

24
Q

How does Cyclophosphamide work?

A

It’s a nitrogen mustard, used to decrease DNA synthesis/formation of immune cells

25
Q

How does Cyclosporine work?

A

Inhibits T and B lymphocyte function

26
Q

How does Azathioprine work?

A

Inhibits T and B lymphocyte function

27
Q

How does Mycophenolate work?

A

Inhibits T and B lymphocyte function

28
Q

What is Etanercept?

A

Human P75 TNF receptor with Fc fragment from IgI1

This binds human TNF to prevent the inflammatory cascade

29
Q

Is Etanercept effective?

A

75% respond to the drug

30
Q

How is Etanercept administered?

A

SubQ injections 2x a week

31
Q

Adverse effects of Etanercept?

A
Pruritus
Swelling
Pain at the injection site
Headache
Cough
Asthenia
Abdominal pain
Serious infections
Osteomyelitis
Pyelonephritis
Pneumonia
32
Q

What is Infliximab?

A

Human-murine monoclonal antibody to TNF-alpha

Also used in crohn’s disease, ulcerative colitis

33
Q

How is Infliximab administered?

A

IV at 4 to 12 week intervals

Can be used with methotrexate

34
Q

Adverse effects of Infliximab?

A

Upper respiratory infections
Nausea
Headache
Allergies (bc it has a mouse component)

35
Q

What is Adalimumab?

A

Recombinant human anti-TNFalpha monoclonal antibody

36
Q

How is Adalimumab administered?

A

SubQ 40 mg every other week

Half life is 9 to 14 days

37
Q

Adverse effects of Adalimumab?

A

Opportunistic infections (tuberculosis)
Leucopenia
Allergies

38
Q

What is Tocilizumab?

A

Monoclonal antibody to IL-56

NOT TNF-alpha

39
Q

How is Tocilizumab administered?

A

Its given with methotrexate, thats all I know

40
Q

Adverse effects of Tocilizumab?

A
Gastric perforations
Serious infections
Hypersensitivity reactions
Hypertension
Upper respiratory infections
41
Q

What is Abatacept?

A

It works by fusing the Fc region of IgG1 and extracellular domain of CTLA-4
This causes inhibition of T cell activation

42
Q

How is abatacept administered?

A

SubQ prefilled pen injections

43
Q

Adverse effects of Abatacept?

A

Headache
Dizziness
Secondary malignancy
Infections (upper respiratory)

Pregnancy category C

44
Q

When do we use Abatacept?

A

For rheumatoid arthritis after inadequate response to TNF-alpha

45
Q

What is penicillamine?

A

Penicillin analog, binds metal ions
Used to prevent active erosive arthritis

Inhibits lymphocyte function by depressing T-cells, reducing cytokines

46
Q

How long does Penicillamine take to work?

A

2-3 months

47
Q

Adverse effects of Penicillamine?

A

Renal toxicity
Sensitivity reactions
Hematological problems

48
Q

What is sulfasalazine?

A

Similar to penicillamine (Inhibits lymphocyte function by depressing T-cells, reducing cytokines)

Used to prevent erosive disease

Both antibacterial and anti-inflammatory actions

49
Q

What is Hydroxychloroquine?

A

Antimalarial with immunosuppressive actions

Decreases chemotaxis, decreases T cells, decreases free radicals

50
Q

What is Hydroxychloroquine used for?

A

Mainly used to induce remission, not used long term

51
Q

Toxicities for Hydroxychloroquine?

A

Irreversible retinal damage
Hematological problems
Seizures