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Pharmacology > Drugs for Rheumatoid Arthritis and Gout > Flashcards

Drugs for Rheumatoid Arthritis and Gout Flashcards

1
Q

What are some of the drugs used to alleviate joint pain?

A
  • NSAIDs
  • Analgesics
  • Glucocorticoids
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2
Q

What are the Disease-Modifying Anti-Rheumatic Drugs (DMARDS)?

A
  • Methotrexate
  • Hydroxychloroquine
  • Sulfasalazine
  • Leflunomide
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3
Q

Hydroxychloroquine Indication

A

Anti-malarial drug that is moderately effective for mild Rheumatoid Arthritis

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4
Q

Hydroxychloroquine MOA

A

a) inhibition of TLR signaling in dendritic/B cells

b) inhibition of antigen presentation to T cells

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5
Q

Hydroxychloroquine SE

A

Rare ocular toxicity

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6
Q

Hydroxychloroquine and Pregnancy

A

Safe during pregnancy and lactation

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7
Q

Sulfasalazine MOA

A

Thought to interfere with T and B cell immune responses - possibly inhibits activation of NF-􏰁B transcription factor

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8
Q

Sulfasalazine and Pregnancy

A

Safe during pregnancy

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9
Q

Sulfasalazine SE

A
  • Agranulocytosis within 2 weeks - very rare

- Hepatotoxicity

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10
Q

Methotrexate MOA

A

Indirectly increases the production of adenosine which exhibits known immunosuppressive properties
• decreases the appearance of new bone erosions
• improves the long term clinical outcome.

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11
Q

Methotrexate Indications

A

Active rheumatoid arthritis that is moderate to severe

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12
Q

Methotrexate SE

A
  • Dose related hepatotoxicity
  • Bone marrow suppression
  • Increased risk of lymphoma
  • Pulmonary toxicity
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13
Q

Methotrxate Contraindications

A
  • Pregnancy
  • Renal Disease
  • Liver Disease
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14
Q

Leflunomide Indications

A
  • alternative for those unable to take, or non-responsive to MTX
  • low cost alternative to TNF inhibitors, or those with a preference for oral medications
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15
Q

Leflunomide MOA

A
  • Inhibits the enzyme dihydroorotate dehydrogenase - uridine synthesis (building block of RNA) - leads to G1 cell cycle arrest
  • Inhibits both T cell proliferation and the production of autoantibodies by B cells
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16
Q

Leflunomide SE

A
  • Hypertension - especially with concurrent NSAIDs
  • Diarrhea, nausea and rash
  • Hepatoxicity - more severe with concurrent methotrexate
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17
Q

Leflunomide Contraindications

A
  • Pregnancy/Breast feeding

- Pre-existing liver disease

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18
Q

What are the TNF-􏰀alpha inhibitors?

A
  • Etanercept
  • Infliximab
  • Adalimumab
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19
Q

Etanercept/Adlimumab/Infliximab MOA

A

Binds to TNF-alpha􏰀 and prevents its interaction with its receptor

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20
Q

Etanercept/Adlimumab/Infliximab Indications

A

Active RA

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21
Q

Etanercept/Adlimumab/Infliximab SE

A
  • Increased risk of infections
  • Potential reactivation of latent tuberculosis and latent HBV
  • RARE exacerbation of pre-existing congestive heart failure
  • RARE development of demyelinating disorders
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22
Q

Etanercept/Adlimumab/Infliximab Contraindications

A

Treatment should be discontinued if a serious infection or sepsis develops - not for patients with acute or chronic infections

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23
Q

Abatacept Indications

A

Active RA - used in pts not responsive to TNF-alpha􏰀 inhibitors

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24
Q

Abatacept MOA

A

Binds CD80/CD86 Blocks T cell co-stimulation via CD28

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25
Q

Abatacept SE

A

Increased risk of serious infections - screen for TB and HBV

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26
Q

Abatacept Contraindications

A

Should not be given in combination with a TNF-􏰀 blocker or to patients with infection

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27
Q

Rituximab Indications

A

Active RA - Effective in patients not responsive to TNF-􏰀alpha inhibitors

28
Q

Rituximab MOA

A

Binds to CD20 on B cells and leads to the depletion of B cells

29
Q

Rituximab SE

A
  • Increased risk of infection
  • Progressive multifocal leukoencepalothapy (PML) -> RARE
  • Reactivation of latent viruses
30
Q

Effects not seen for 3 months, although effects may last 6 months - 2 yrs following a single infusion.

A

Rituximab

31
Q

Anakinra MOA

A

IL-1 receptor antagonist

32
Q

Anakinra Indications

A

Active RA

33
Q

Anakinra SE

A
  • Increased risk of neutropenia
  • Increased risk of serious infections
  • Increased risk of malignancy
34
Q

Anakinra Contraindications

A

Should not be given to patients with acute/chronic infections

35
Q

Tocilizumab Indications

A

Active RA in pots non-responsive to TNF inhibitors or in combination therapy with MTX (methotrexate)

36
Q

Tocilizumab MOA

A

IL-6 receptor antagonist

37
Q

Tocilizumab SE

A
  • Increased risk of bone marrow suppression
  • Increased risk of serious infections -> TB and HBV
  • Hepatotoxicity
  • Increased levels of cholesterol
  • Increased risk of malignancy
38
Q

Tocilizumab Contraindications

A
  • Patients with acute/chronic infections
  • Patients with pre-existing liver disease
  • Patients with low blood counts

***Should not be combined with other Biologics - none of the biologics should be combined

39
Q

Tofacitinib Indications

A

Active RA

40
Q

Tofacitinib MOA

A

Small molecule inhibitor that inhibits JAK tyrosine kinases involved in immune cell cytokine signaling

41
Q

Tofacitinib SE

A
  • Lymphocytopenia, neutropenia and anemia
  • Increased risk of serious infections including TB
  • Increased cholesterol
  • Increased liver enzymes
42
Q

Tofacitinib Contraindications

A

Not for pts with acute/chronic infections

43
Q

What are tophi?

A

Urate crystal deposits around the joint that promote inflammation and joint destruction

44
Q

Indications of NSAIDs in Gout

A

Decreases pain and disability due to acute gouty attack

45
Q

Colchicine Indications

A

Acute Gouty Attack

46
Q

Colchicine MOA

A

Inhibits tubulin polymerization which blocks leukocyte migration/phagocytosis

47
Q

Colchicine SE

A

Very narrow therapeutic window and almost always causes vomiting, nausea and diarrhea

48
Q

Does colchicine have analgesic effects?

A

No

49
Q

What type of drug is probenicid?

A

Uricosuric - increases uric acid excretion

50
Q

Probenecid Indications

A

Chronic gout due to decreased uric acid excretion

51
Q

Probenecid MOA

A

Weak organic acid inhibits anion transporters in the proximal renal tubules involved in the reabsorption of uric acid

52
Q

Probenecid SE

A

Can cause kidney stones

53
Q

Probenecid Contraindications

A
  • Kidney stones
  • Renal insufficiency
  • Uric acid overproduction
54
Q

When should probenecid NOT be given?

A

Should not be given until 2-3 weeks after the initial attack - drug can actually initiate and/or prolong the symptoms of an acute gouty attack

55
Q

Why does probenecid have many DDIs?

A

It inhibits the URAT1 transporter, which many drugs (ex: indomethacin, naproxen, lorazepam, cephalosporins, methotrexate, captopril, AZT and ganciclovir) utilize for reabsorption.

56
Q

What are the xanthine oxidase inhibitors?

A
  • Allopurinol

- Feboxostat

57
Q

Allopurinol/Feboxostat Indications

A

Used in the treatment of chronic gout to block overproduction of uric acid
- Good for patients with a history of uric acid kidney stones

58
Q

Allopurinol/Feboxostat MOA

A

Inhibits xanthine oxidase

59
Q

Allopurinol/Feboxostat SE

A
  • Rash, leukopenia, thromobocytopenia & fever can occur in 3-5% of patients
  • RARE SE is allopurinol hypersensitivity syndrome (only in allopurinol)
60
Q

Allopurinol Hypersensitivity Syndrome

A
  • potentially life threatening reaction (25% mortality rate)
  • symptoms include: erythematous rash, fever, hepatitis, eosinophilia and acute renal failure
  • most likely to occur in patients taking excessive doses of drug in the presence of pre-existing renal failure and/or use of diuretics
61
Q

What ethnicities are at increased risk of allopurinol hypersensitivity syndrome?

A

Han Chinese, Korean and Thai

62
Q

What are the main DDIs of allopurinol/feboxostat?

A

6-mercaptopurine and azathioprine - have increased toxicity as their metabolism is inhibited (xanthine oxidase is inhibited)

63
Q

Pegloticase Indications

A

Advanced, actively symptomatic gout - uncontrolled with other uric acid lowering drugs

64
Q

Pegloticase MOA

A

Porcine uricase linked to PEG (polyethylene glycol) and the pig uricase enzyme allows for conversion of uric acid to a soluble metabolite

65
Q

Pegloticase SE

A

Generally well tolerated but generation of anti-drug antibodies limits treatment

66
Q

What prophylaxis does pegloticase require?

A

Requires NSAID/Colchicine prophylaxis

Pharmacology (74 decks)

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