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Block 3 > Lecture 133/134 > Flashcards

Lecture 133/134 Flashcards

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1
Q

Methotrexate belongs to which pharmacological class?

A

Conventional synthetic

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2
Q

Sulfasalazine belongs to which pharmacological class?

A

Conventional synthetic DMARDs

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3
Q

Hydroxychloroquine belongs to which pharmacological class?

A

Conventional synthetic DMARDs

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4
Q

Leflunomide belongs to which pharmacological class?

A

Conventional synthetic DMARDs

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5
Q

Biological DMARDs include:

A

Anti-TNF inhibitors, IL-6 recepot antagonists, T-cell costimulation blockers, B-cell depleteing drugs

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6
Q

Tofacitinib belongs to which pharmacological class?

A

Targeted synthetic DMARDs; JAK inhibitor

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7
Q

Where is rheumatoid factor produced within the body?

A

B-cells

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8
Q

Patients should be screened for what infectious diseases before initiating DMARD therapy?

A

TB, hep B/C

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9
Q

What DMARDs are contraindicated in pregnancy?

A

Methotrexate & leflunomide

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10
Q

What DMARDs are considered relatively safe during pregnancy?

A

Hydroxychloroquine and sulfasalazine

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11
Q

What is the main human glucocorticoid?

A

Cortisol

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12
Q

What structural feature is crucial for glucocorticoid activity?

A

4,5 double bond on the A ring

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13
Q

How do glucocorticoids exert genomic effects?

A

By binding to glucocorticoid response elements (GREs) to alter gene transcription

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14
Q

What effect of glucocorticoids results in less prostaglandin synthesis?

A

Reduced COX-2 expression

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15
Q

Abrupt withdrawal of glucocorticoids can put patients at risk for:

A

Acute adrenal insufficiency (adrenal crisis)

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16
Q

What DMARD is a folate analog and antimetabolite?

A

Methotrexate

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17
Q

What supplement should be taken alongside methotrexate?

A

Folic acid

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18
Q

How is methotrexate metabolized?

A

Partly intracellularly and by gut flora

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19
Q

MTX MOA:

What is the result of dihydrofolate reductase (DHFR) inhibition?

A

Blocks DNA/RNA synthesis and limits cell proliferation of lymphocytes

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20
Q

MTX MOA:

What is the result of thymidylate synthase (TYMS) inhibition?

A

Impairs nucleotide synthesis resulting in an antiproliferative effect

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21
Q

MTX MOA

What is the result of AICAR transformylase (ATIC) inhibition?

A

Extracellular adenosine accumulation resulting in an antiinflamamtory/immunosuppressive effect

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22
Q

What are the three MOA of MTX?

A
  • DHFR inhibition
  • TYMS inhibition
  • ATIC inhibition
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23
Q

What are the major antiproliferative effects of MTX?

A

Inhibits lymphocyte, macrophage, and dendritic cell proliferation

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24
Q

What are the major anti-inflammatory effects of MTX?

A

Increases adenosine and supresses proinflammatory mediators

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25
How long does it take to see antirheumatic effects of MTX?
3-6 weeks
26
What are the common hematological adverse effects of MTX?
Cytopenias (leukopenia, thrombocytopenia) and pancytopenia
27
What is a rare but serious pulmonary complication of MTX?
MTX pneumonitis
28
Folate acid supplementation helps reduce which adverse effects of MTX?
GI, liver, and hematologic side effects
29
Agents inhibiting which transporters can raise MTX levels and increase toxicity risk?
OAT or P-gp inhibitors (e.g. NSAIDs, certain antibitoics)
30
Drugs such as salicylates, sulfonamides, and phenytoin interact with MTX by what mechanism?
They can displace MTX from plasma protein binding, resulting in toxicity
31
Patients on MTX should not receive what preventative care?
Live vaccinations
32
Sulfasalazine is cleaved by gut flora into:
Sulfapyridine (active in RA) and mesalamine (5-ASA)
33
What DMARD is often used in mild RA?
Hydroxychloroquine (HCQ)
34
How long is the onset of HCQ?
6 weeks to 6 months
35
The mechanism of HCQ may involve:
Altering lyosomal pH
36
What toxicity is specific to HCQ?
Ocular toxicity (retinopathy)
37
Leflunomide is converted to:
Teriflunomide
38
What is the mechanism of action of leflunomide?
Inhibits dihydroorotate dehydrogenase (pyrimidine synthesis) resulting in cell cycle arrest
39
Why does leflunomide have a long half-life?
Enterohepatic circulation
40
Infliximab belongs to which pharmacological class?
Anti-TNF bDMARDs
41
Adalimumab belongs to which pharmacological class?
Anti-TNF bDMARDs
42
Etenercept belongs to which pharmacological class?
Anti-TNF bDMARDs
43
How long do anti-TNF agents take to see effect?
Within 2 weeks
44
Anti-TNF agents have the potential to increase the risk of what malignancy?
Lymphoma
45
Tocilizumab belongs to which pharmacological class?
IL-6 receptor antagonist bDMARDs
46
Common adverse effects of IL-6 receptor antagonists:
- URI - Headache - HTN - Elevated liver enzymes - Hyperlipidemia
47
Abatacept belongs to which pharmacological class?
bDMARDs
48
What is the MOA of Abatacept?
T-cell costimulation blocker --> binds CD80/B7 on APC
49
Rituximab belongs to which pharmacological class?
bDMARDs
50
What is the MOA of rituximab?
B-cell depletion via complement-mediated cytotoxicity
51
Which dMARD carries a risk of PML?
Rituximab
52
Tofacitinib belongs to which pharmacological class?
JAK inhibitor tsDMARDs
53
What is the MOA of JAK inhibitors?
Block phosphorylation and activation of STAT pathways
54
What are the serious adverse effects of JAK inhibitors?
- Serious infection - Malignancy - Thrombosis
55
TNF inhibitors can be used in pregnancy up until ____ weeks
32 weeks
56
Sulfasalazine has a high affinity for what tissues?
Connective tissues
57
How long is the onset of sulasalazine in the use of RA?
6 weeks-3 months
58
Salfasalazine can also be used to treat ____
Juvenile idiopathic arthritis
59
What DMARDs carry a risk of SJS, TEN, and DRESS?
Sulfasalazine, leflunomide
60
Hemolytic anemia can be seen in people with G6PD deficiency taking what DMARD?
Sulfasalazine
61
What is a possible reversible side effect of sulfasalazine?
Oligospermia
62
What is the Black Box warning for leflunomide?
Severe liver injury (fulminant hepatic necrosis)
63
How is infliximab administered?
IV infusion q8 weeks
64
Which anti-TNF agent only binds soluble TNF-a?
Entanercept
65
Which anti-TNF DMARD is a fusion protein of two TNF receptors?
Entanercept
66
How is entanercept administered?
SubQ 1-2 times/week
67
How is adalimumab administered?
SubQ every other week
68
How is tocilizumab administered?
IV q4 weeks or subQ weekly
69
Which bDMARD is also occasionaly used to treat severe COVID-19?
Tocilizumab
70
What are the possible adverse effects of tocilizumab?
Neutropenia, elevated LFTs, dyslipidemia
71
Which bDMARD is a fusion protein of CTLA-4 + IgG Fc?
Abatacept
72
What is the binding target for abatacept?
CD-80/B7 on APCs
73
How is abatacept administered?
IV monthly or subQ weekly
74
How is rituximab administered?
IV infusion q24 weeks
75
What DMARD is metabolized by CYP3A4?
Toficitnib
76
JAK inhibitors should not be used in combination with ____
bDMARDs

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