Drugs to treat RA and gout Flashcards Preview

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Flashcards in Drugs to treat RA and gout Deck (105):
1

Which cytokines are involved in RA?

TNFa, IL-6, IL-1, PG

2

Drugs to decrease acute joint pain

NSAIDS (indomethacin, naproxen)
Analgesics (acetaminophen, capsacin, opioids)
Glucocorticoids (dexamethasone)

3

What do you typically use NSAIDS/analgesics/glucocorticoids for in the rx of RA?

minimize symptomatic effects of disease while waiting for clinical effects of slow acting DMARDS/BRMs

4

DMARDS

Disease Modifying Anti-Rheumatic Drugs (DMARDs)

5

DMARDS indication

reduce/prevent joint damage

6

How long till DMARDS show efficacy?

Weeks to months

7

Commonly used DMARDS

Hydroxychloroquine, Sulfasalazine, Methotrexate, Leflunomide

8

Less frequently used DMARDS

Azathioprine, D-Penicillamine, Gold Salts, Cyclosporin, Cyclophosphamide

9

Hydroxychloroquine Indication

Mild RA

10

Which RA drug is a anti-malarial drug?

Hydroxychloroquine

11

Hydroxychloroquine MOA

inhibition of TLR signaling/ antigen presentation to T cells

12

Hydroxychloroquine time to effect

3-6 months

13

Which drugs are often given in combination with Hydroxychloroquine

sulfasalazine
Methotrexate

14

Is hydroxychloroquine safe in pregnancy/lactation?

YEs

15

Rare side effect of hydroxychloroquine

Ocular toxicity

16

Sulfasalazine

Decreases signs and symptoms of disease
Slow joint destruction
*More toxic than hydroxychloroquine
*Similar efficacy to methotrexate

17

What is the active component of sulfasalazine?

sulfapyridine

18

Sulfasalazine MOA

? interfer with T/B cell immune response
Inhibits NF-KB

19

Sulfasalazine time to effect

1-3 months

20

Is sulfasalazine safe during pregnancy?

Yes

21

Which other DMARDS is sulfasalazine often combined with

Hydroxychloroquine

22

Adverse effects of sulfasalazine

Agranulocytosis
Hepatotoxicity *reversible

23

Methotrexate

DRUG OF CHOICE for active moderate/severe disease

Decreases appearance of new bone erosions
Improves long term clinical outcome

24

Methotrexate time to effect

4-6 weeks

25

Methotrexate MOA

increases production of adenosine > immunosuppressive

26

Common side effect of Methotrexate

hepatoxicity

27

What should patients on methotrexate obtain from?

Alcohol

28

Rare side effects of methotrexate?

Pulmonary toxicity
Bone marrow suppression
Increased risk of lymphoma

29

Methotrexate is contraindicated in?

pregnancy/breast feeding
pre-existing liver disease
renal impairment

30

How is methotrexate excreted?

80-90% renally

31

is methotrexate safe in pregnant?

NO!

32

Leflunomide

= effective to sulfasalazine and methotrexate
Low cost alternative to TNF inhibtors

33

Leflunomide time to effect

1-2 months

34

Leflunomide MOA

inhibits dihydroorotate dehydrogenase, decreases synthesis of uridine

35

Adverse effects of Leflunomide

HTN (w/ NSAIDS)
Diarrhea, nausea, rash
Hepatotoxicity (w/ methotrexate)

36

What is Leflunomide contraindicated in?

Pregnancy/breast feeding
Pre-existing liver disease

37

Biologic response modifiers

specifically designed to inhibit either cytokines (TNFa, IL-6, IL-1) or cell types (T-cells, B-cells)

38

Which cells synthesize TNF-a?

CD 4+T cells, macs, mast cells

39

What does TNF-a cause?

Joint inflammation (endothelials)
Cartilage breakdown (chondrocyte/synoviocyte)
Bone erosion (osteoclast)

40

How are anti-TNFa drugs given?

SQ or IV

41

How often are TNF-a drugs given?

Weekly/biweekly

42

Anti TNFa drugs time to effect

1-4 weeks

43

Effects of anti-TNFa

Decrease join pain and swelling
Decreased formation of new bone erosions
Decreased progression of structural joint damage

44

What can the anti-TNFa drugs be used in combo with?

Methotrexate

45

Adverse effects of anti-TNFa

increased risk of infections
Potential reactivation of latent TB, HBV
Exacerbation of pre-existing CHF
Developing of demyelinating disease (MS)

46

What are the 3 anti-TNFa drugs?

Etanercept
Infliximab
Adalimumab

47

Abatacept MOA

Recombinant CTLA4+ IgG
Inhibits T cell activation

48

Abatacept Indication

slows damage to bone and cartilage
effective in pts non-responsive to TNF-a inhibitors

49

Abatacept adverse effects

Increase risk of infection

50

Abatacept contraindication

DO not give with TNF-a blocker

51

Rituximab MOA

binds CD20
Depletes B cells

52

Rituximab time to effect

3 months

53

How long do the effects of rituximab last?

6 months- 2 years with one infusion

54

Rituximab adverse effects

Increased infections
Reactivation of latent viruses (CMV, HSV, HBV, HCV)
PML

55

Anakinra

Anti- IL-1R
Competitively inhibits the pro-inflammatory effects of IL-1
* less effective than anti-TNFa

56

What is the half life of anakinra?

short (4-6 hours)

57

How often must you give anakinra and how administered?

Sub Q once a day

58

Anakinra adverse effects

Neutropenia
Serious infections
* complications more frequent when given with Anti-TNF-a

59

Tocilizumab

anti- IL-6 R

60

Indications of Toxilizumab

Patients non-responsive to TNF inhibitors
or in combo with methotrexate

61

Tocilizumab Adverse effects

BM suppression
serious infection
Hepatotoxicity
Increased cholesterol
Increased malignancy

62

Tocilizumab Contraindications

pre-existing liver disease
Low blood counts/immunosuppresives

63

Tofacitinib

Small molecule inhibitor of cytokine signaling (anti-JAK)

64

Tofacitinib adverse effects

BM suppression
serious infections
Increased cholesterol
Hepatotoxicity

65

What co-morbidities is gout associated with?

obesity
HTN
hyperlipidemia
DM II
Hyperuricemia

66

What is a high serum uric acid

>7 mg/dL

67

What is the most common cause of high serum uric acid?

Decreased excretion

68

Which joint is often first affected in gout?

first metatarophalangeal joint

69

What are tophi?

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

70

Treatment of acute gout (relieve symptoms)

Clochicine
NSAIDS

71

Treatment of Chronic Gout

Drugs that lower uric acid levels by promoting excretion
Drugs that lower uric acid levels by inhibiting synthesis
Drugs that directly degrade uric acid

72

Drugs that lower uric acid levels by promoting excretion

Probenecid
Lesinurad

73

Drugs that lower uric acid levels by inhibiting synthesis

Allopurinol
Febuxostat

74

Drugs that directly degrade uric acid

Pegloticase

75

Which NSAIDS are used to treat gouty attack

Indomethacin
Naproxen

76

How do NSAIDS help in gout?

Reduce production of prostaglandins

77

Indication of NSAIDS in gout?

prophylactic Rx (w/ other anti-gout drugs)
relieve symptoms of acute gouty attack

78

Which drugs are NOT used in treated acute gouty attack?

Aspirin
Salicylates

79

Colchicine MOA

Prevents tubulin polymerization into microtubules
Decreases leukocyte migration and phagocytosis

80

Colchicine effects

Anti-inflammatory
NOT analgesic

81

When should you give colchicine

within 24-48 hours of attack

82

Colchicine side effects

Narrow therapeutic window
Nausea, vomiting, diarrhea

83

Probenecid

inhibits anion transporters (URAT1) in proximal renal tubules that reabsorb uric acid > increased uric acid excretion

84

Probenecid indications

Patient that under excrete uric acid

85

When should you give probenecid

2-3 weeks after initial attack

86

What is the risk of giving probenecid too early?

Can initiate/ prolong acute gouty attach

87

What should you give with probenecid prophylactically?

NSAIDs

88

Probenecid contraindications

pts who overproduce uric acid
pts w/ kidney stones
pts with renal insufficiency

89

Drug interactions with Probenecid

Probenecid increases excretion of drugs that are normally reabsorbed by URAT1 (indomethacin, naproxen, lorazepam, cephalosporins, methotrexate, captopril, AZTM ganciclovir)

90

Allopurinol
Febuxostat

Inhibits xanthine oxidase

91

Allopurinol
Febuxostat Indications

high level of uric acid synthesis
recurrent kidney stones
renal impairment
TOPHI

92

Adverse effects of allopurinol and febuxostat

induce acute gout attack if NSAID not provided

Rash, leukopenia, thrombocytopenia

93

Rare side effect of allopurinol

allopurinol hypersensitivity syndrome

94

allopurinol hypersensitivity syndrome

life threatening
-excessive doses, renal failure, diuretics, HLA-B*5801 allele

95

Which gene is associated with allopurinol hypersensitivity syndrome

HLA-B*5801

96

What drugs interact with allopurinol and febuxostat

6-mercaptopurine
Azathioprine

97

If a patient has hyperuricemia, but no symptoms, do you treat?

NO

(unless VERY high >12)

98

What is our goal for serum uric acid levels?

99

Effective therapy of gout will require treatment for how long

life time

100

Treatment of drug-resistant chronic gout

Pegloticase

101

Pegloticase MOA

Enzymatic conversion of URIC acid to soluble metabolite

102

Pegloticase Indication

Advanced, active gout
Uncontrolled with other drug

103

How often do you give pegloticase, how is it administered?

IV infusion, every 2 weeks

104

How quickly is pegloticase effective

months

105

Adverse effects of pegloticase

Anti-drug antibodies