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Drugs to treat RA and gout Flashcards

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1
Q

Which cytokines are involved in RA?

A

TNFa, IL-6, IL-1, PG

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2
Q

Drugs to decrease acute joint pain

A

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

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3
Q

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

A

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

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4
Q

DMARDS

A

Disease Modifying Anti-Rheumatic Drugs (DMARDs)

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5
Q

DMARDS indication

A

reduce/prevent joint damage

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6
Q

How long till DMARDS show efficacy?

A

Weeks to months

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7
Q

Commonly used DMARDS

A

Hydroxychloroquine, Sulfasalazine, Methotrexate, Leflunomide

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8
Q

Less frequently used DMARDS

A

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

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9
Q

Hydroxychloroquine Indication

A

Mild RA

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10
Q

Which RA drug is a anti-malarial drug?

A

Hydroxychloroquine

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11
Q

Hydroxychloroquine MOA

A

inhibition of TLR signaling/ antigen presentation to T cells

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12
Q

Hydroxychloroquine time to effect

A

3-6 months

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13
Q

Which drugs are often given in combination with Hydroxychloroquine

A

sulfasalazine

Methotrexate

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14
Q

Is hydroxychloroquine safe in pregnancy/lactation?

A

YEs

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15
Q

Rare side effect of hydroxychloroquine

A

Ocular toxicity

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16
Q

Sulfasalazine

A

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

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17
Q

What is the active component of sulfasalazine?

A

sulfapyridine

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18
Q

Sulfasalazine MOA

A

? interfer with T/B cell immune response

Inhibits NF-KB

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19
Q

Sulfasalazine time to effect

A

1-3 months

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20
Q

Is sulfasalazine safe during pregnancy?

A

Yes

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21
Q

Which other DMARDS is sulfasalazine often combined with

A

Hydroxychloroquine

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22
Q

Adverse effects of sulfasalazine

A

Agranulocytosis

Hepatotoxicity *reversible

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23
Q

Methotrexate

A

DRUG OF CHOICE for active moderate/severe disease

Decreases appearance of new bone erosions
Improves long term clinical outcome

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24
Q

Methotrexate time to effect

A

4-6 weeks

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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

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