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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
Abatacept SE
Increased risk of serious infections - screen for TB and HBV
26
Abatacept Contraindications
Should not be given in combination with a TNF-􏰀 blocker or to patients with infection
27
Rituximab Indications
Active RA - Effective in patients not responsive to TNF-􏰀alpha inhibitors
28
Rituximab MOA
Binds to CD20 on B cells and leads to the depletion of B cells
29
Rituximab SE
- Increased risk of infection - Progressive multifocal leukoencepalothapy (PML) -> RARE - Reactivation of latent viruses
30
Effects not seen for 3 months, although effects may last 6 months - 2 yrs following a single infusion.
Rituximab
31
Anakinra MOA
IL-1 receptor antagonist
32
Anakinra Indications
Active RA
33
Anakinra SE
- Increased risk of neutropenia - Increased risk of serious infections - Increased risk of malignancy
34
Anakinra Contraindications
Should not be given to patients with acute/chronic infections
35
Tocilizumab Indications
Active RA in pots non-responsive to TNF inhibitors or in combination therapy with MTX (methotrexate)
36
Tocilizumab MOA
IL-6 receptor antagonist
37
Tocilizumab SE
- Increased risk of bone marrow suppression - Increased risk of serious infections -> TB and HBV - Hepatotoxicity - Increased levels of cholesterol - Increased risk of malignancy
38
Tocilizumab Contraindications
- 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
Tofacitinib Indications
Active RA
40
Tofacitinib MOA
Small molecule inhibitor that inhibits JAK tyrosine kinases involved in immune cell cytokine signaling
41
Tofacitinib SE
- Lymphocytopenia, neutropenia and anemia - Increased risk of serious infections including TB - Increased cholesterol - Increased liver enzymes
42
Tofacitinib Contraindications
Not for pts with acute/chronic infections
43
What are tophi?
Urate crystal deposits around the joint that promote inflammation and joint destruction
44
Indications of NSAIDs in Gout
Decreases pain and disability due to acute gouty attack
45
Colchicine Indications
Acute Gouty Attack
46
Colchicine MOA
Inhibits tubulin polymerization which blocks leukocyte migration/phagocytosis
47
Colchicine SE
Very narrow therapeutic window and almost always causes vomiting, nausea and diarrhea
48
Does colchicine have analgesic effects?
No
49
What type of drug is probenicid?
Uricosuric - increases uric acid excretion
50
Probenecid Indications
Chronic gout due to decreased uric acid excretion
51
Probenecid MOA
Weak organic acid inhibits anion transporters in the proximal renal tubules involved in the reabsorption of uric acid
52
Probenecid SE
Can cause kidney stones
53
Probenecid Contraindications
- Kidney stones - Renal insufficiency - Uric acid overproduction
54
When should probenecid NOT be given?
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
Why does probenecid have many DDIs?
It inhibits the URAT1 transporter, which many drugs (ex: indomethacin, naproxen, lorazepam, cephalosporins, methotrexate, captopril, AZT and ganciclovir) utilize for reabsorption.
56
What are the xanthine oxidase inhibitors?
- Allopurinol | - Feboxostat
57
Allopurinol/Feboxostat Indications
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
Allopurinol/Feboxostat MOA
Inhibits xanthine oxidase
59
Allopurinol/Feboxostat SE
- Rash, leukopenia, thromobocytopenia & fever can occur in 3-5% of patients - RARE SE is allopurinol hypersensitivity syndrome (only in allopurinol)
60
Allopurinol Hypersensitivity Syndrome
- 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
What ethnicities are at increased risk of allopurinol hypersensitivity syndrome?
Han Chinese, Korean and Thai
62
What are the main DDIs of allopurinol/feboxostat?
6-mercaptopurine and azathioprine - have increased toxicity as their metabolism is inhibited (xanthine oxidase is inhibited)
63
Pegloticase Indications
Advanced, actively symptomatic gout - uncontrolled with other uric acid lowering drugs
64
Pegloticase MOA
Porcine uricase linked to PEG (polyethylene glycol) and the pig uricase enzyme allows for conversion of uric acid to a soluble metabolite
65
Pegloticase SE
Generally well tolerated but generation of anti-drug antibodies limits treatment
66
What prophylaxis does pegloticase require?
Requires NSAID/Colchicine prophylaxis

Pharmacology (74 decks)

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