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Pharmacology > RA and Gout Drugs > Flashcards

RA and Gout Drugs Flashcards

1
Q

What drugs are used for symptomatic relief of RA?

A

Analgesics, NSAID, and glucocorticoids - used early in onset of disease while waiting for effects of DMARDs/BRMs

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2
Q

Is Hydroxychloroquine used to treat mild or severe RA?

A

Mild

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3
Q

How long to see effects of Hydroxychloroquine?

A

3-6 months

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4
Q

Can you combine Hydroxychloroquine with other drugs?

A

YES - Sulfasalazine and Methotrexate

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5
Q

Can Hydroxychloroquine be used during pregnancy?

A

YES - safe for pregnancy and lactation

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6
Q

What is a rare but serious side effect of Hydroxychloroquine?

A

Ocular toxicity - can result in permanent vision loss

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7
Q

How long to see effects of Sulfasalazine?

A

1-3 months

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8
Q

Can Sulfasalazine be used during pregnancy?

A

YES!

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9
Q

What are potential side effects of Sulfasalazine use?

A

Can lead to agranulocytosis (often within 2 weeks of starting; reversible) and hepatotoxicity

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10
Q

What is the drug of choice for treating moderate to severe RA?

A

Methotrexate

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11
Q

Wait…isn’t Methotrexate used in cancer?

A

YES! However, in RA it is used in a much lower dose (1000x lower) and works via a different mechanism

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12
Q

Major clinical benefit of Methotrexate

A

Decreased appearance of new bone erosions

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13
Q

What is a common side effect of Methotrexate?

A

Dose-related hepatotoxicity - abstain from alcohol when using

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14
Q

What are some rare side effects of Methotrexate?

A

Pulmonary toxicity, bone marrow suppression, increased risk of lymphoma - have to be clinically monitored while taking Methotrexate to ensure these don’t happen

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15
Q

How is Methotrexate excreted?

A

Renally - patients with renal impairment at greater risk of developing side effects

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16
Q

What are some Methotrexate contraindications?

A

Pregnancy - may lead to abortion

Not recommended for patients with liver disease or renal impairment

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17
Q

What is an alternative if patient cannot use Methotrexate?

A

Leflunomide

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18
Q

Leflunomide MOA

A

Inhibits dihydroorotate dehydrogenase - inhibits both T cell proliferation and production of autoantibodies by B cells

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19
Q

What are some adverse effects of Leflunomide?

A

Hypertension (especially with NSAID use), diarrhea, nausea, rash, HEPATOTOXICITY (more severe in patients taking methotrexate, make sure to monitor liver enzymes)

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20
Q

What are three TNF-alpha inhibitors?

A

Etanercept, Adalimumab, and Infliximab

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21
Q

TNF-alpha inhibitor MOA

A

Bind to soluble TNF-alpha and prevent it from interacting with its receptor and inducing a biological response

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22
Q

How are TNF-alpha inhibitors administered?

A

Subcutaneous injection or IV - administered weekly/biweekly

23
Q

Can TNF-alpha inhibitors be used as a monotherapy?

A

Yes, but may also be used with methotrexate

24
Q

What are adverse effects associated with TNF-alpha inhibitors?

A

Increased risk of opportunistic infections (fungal and bacterial), potential reactivation of latent TB and latent HBV
Do not give to anyone with an acute or chronic infection - decreases immune response and can be fatal

25
Q

What are rare side effects of TNF-alpha inhibitors?

A

Exacerbation of pre-exisiting CHF, development of demyelinating disorders (MS), appearance of malignancies, especially lymphoma

26
Q

Abatacept MOA

A

Inhibits T cell activation by blocking delivery of CD28 co-stimualatory signal necessary for T cell activation
Can be used in patients not responsive to TNF-alpha inhibitors

27
Q

What are adverse effects associated with Abatacept?

A

Increased risk of serious infection - screen for latent TB and HBV

28
Q

Can Abatacept be used in conjunction with TNF-alpha inhibitors?

A

NO! Will lead to massive immunosuppression

29
Q

Rituximab MOA

A

Binds to CD20 on B cells - IV infusion depletes B cells from the blood
Effective for patients not responsive to TNF-alpha inhibitors

30
Q

How long until you see effects of Rituximab?

A

3 months, however a single infusion may have effects for up to 2 years

31
Q

What are adverse effects associated with Rituximab?

A

Increased infections, reactivation of latent viruses, PML due to reactivation of JC virus

32
Q

Anakinra MOA

A

IL-1 receptor antagonist - completely inhibits pro-inflammatory effects of IL-1

33
Q

What are adverse effects associated with Anakinra?

A

Increased risk of neutropenia, serious infections

Should not be given to patients with acute or chronic infections

34
Q

Tocilizumab MOA

A

Chimeric antibody directed against IL-6 cytokine receptor

Used in patients non-responsive to TNF-alpha inhibitors or in combination with methotrexate

35
Q

What are adverse effects associated with Tocilizumab?

A

Increased risk of bone marrow suppression, serious infection, hepatotoxicity, increased cholesterol, increased risk of malignancy

36
Q

In whom is Tocilizumab contraindicated?

A

Patients with acute/chronic infections, pre-existing liver disease, low blood counts, or patients on immunosuppressive therapy

37
Q

Tofacitinib MOA

A

Inhibits JAK tyrosine kinases involved in immune cell cytokine signaling

38
Q

What adverse effects are associated with Tofacitinib?

A

Lymphopenia, neutropenia, anemia, increased risk of serious infection, lipid abnormalities, increased liver enzymes

39
Q

What class of drugs is used to treat an acute gouty attack?

A

NSAIDs - these are also given prophylactically in combination with other anti-gout drugs

40
Q

What should not be used to treat acute gouty attack?

A

Aspirin and salicylates - inhibit uric acid excretion at low doses and can actually induce gout

41
Q

Is Colchicine used to treat chronic gout?

A

NO - used to treat acute gouty attack and used in combination with other gout drugs for prophylaxis

42
Q

Colchicine MOA

A

Prevents tubulin polymerization into microtubules - decreases leukocyte migration and phagocytosis

43
Q

Colchicine is effective within ____ hours of a gouty attack

A

24-48 hours

44
Q

Are side effects of Colchicine common?

A

YES! Has a very narrow therapeutic window - 80% of patients experience nausea, vomiting, diarrhea

45
Q

What type of gout patient is Probenecid used in?

A

Uric acid underexcreter - do NOT give to patients who overproduce uric acid as this can lead to kidney stones

46
Q

Probenecid MOA

A

Blocks URAT1 transporter - decreases uric acid reabsorption and facilitates uric acid excretion

47
Q

What are contraindications associated with Probenecid?

A

Patients who overproduce uric acid (can lead to kidney stones) and patients with kidney stones or underlying renal insufficiency

48
Q

What patients are Allopurinol and Febuxostat useful for?

A

Patients with grossly elevated uric acid (have tophi), patients with recurrent kidney stones, and patients with renal impairment

49
Q

Allopurinol and Febuxostat MOA

A

Inhibit xanthine oxidase

50
Q

What are side effects associated with Allopurinol and Febuxostat?

A

Can induce acute gouty attack if not taken with NSAIDs. May also cause rash, leukopenia, thrombocytopenia

51
Q

What is a serious side effect associated with Allopurinol use?

A

Allopurinol hypersensitivity syndrome - very life threatening!
Patients have rash, fever, hepatitis, acute renal failure
This is more common in patients taking excessively high doses of the drug w/ renal impairment and/or use of diuretics

52
Q

What drug-drug interactions may occur with Allopurinol or Febuxostat?

A

Toxic levels of 6-mercaptopurine and azathioprine - these are normally metabolized by xanthine oxidase

53
Q

What drug is used to treat drug-resistance chronic gout?

A

Pegloticase

Pharmacology (5 decks)

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