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Pharm: Psych > 3.2: Rheumatoid > Flashcards

3.2: Rheumatoid Flashcards

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1
Q

What is RA?

A
  • Chronic inflammatory disease of the joints that is autoimmune in nature
  • Leads to pain and destruction of the joints
  • Etiology is unknown
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2
Q

Important mediators of RA?

A
  1. IL6 / 1
  2. TNF alpha
  3. T and B cells
  4. Prostaglandins
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3
Q

2 categories of RA drugs?

A
  1. To decrease joint pain
    a. NSAIDs
    b. Analgesics: acetaminophen
    c. Glucocorticoids: dexamethasone
  2. To control joint damage:
    a. DMARDs: “Disease modifying antirheumatic agents”
    b. BRM: Biologic response modifiers”
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4
Q

What is dexamethasone?

A

Glucocorticoid that can be used in symptomatic treatment of RA

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5
Q

Which are the DMARDs?

A
  1. Methotrexate
  2. Sulfasalazine
  3. Hydroxychloroquine
  4. Leflunomide
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6
Q

Characteristics of DMARDs?

A
  • Prevent joint damage and reduce pain
  • Take weeks - months to be efficacious
  • Course is months - years
  • Thought to inhibit the immune system
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7
Q

2 indications of Hydroxychloroquine?

A
  1. Mild RA: often with other DMARDs

2. Malaria

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8
Q

Mechanisms of Hydroxychloroquine?

A
  1. Inhibits TLR signalling in B cells

2. Inhibits APC to T cells

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9
Q

Onset of Hydroxychloroquine?

A

3 - 6 monthsq

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10
Q

Side effects of Hydroxychloroquine?

A
  1. Blindness: higher with LT treatment, high dose, age

* **Safe during pregnancy and lactation

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11
Q

Which DMARD safe for pregnancy / lactation?

A

1 Hydroxychloroquine

2. Sulfasalazine

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12
Q

Relative efficacy and toxicity of Sulfasalazine?

A
  • Similar efficacy to Methotrexate

- More toxic than Hydroxychloroquine

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13
Q

MOA of Sulfasalazine?

A
  • Thought to inhibit T an B cell responses: NFKB
  • Prodrug converted by gut bacteria into sulfapyridine
  • Sulfapyridine is the active component
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14
Q

Onset of Sulfasalazine?

A

1 - 3 months

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15
Q

Side effects of Sulfasalazine?

A
  1. Agranulocytosis: fully reversible, monitor
  2. Hepatotoxicity
    * ***Safe in pregnancy
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16
Q

Drug of choice for active, severe RA?

A

Methotrexate

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17
Q

Other indication for Methotrexate?

A

Cancer: used at 1/100 - 1/1000 dose less for RA

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18
Q

Onset of Methotrexate?

A

4 - 6 weeks

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19
Q

MOA of Methotrexate?

A
  • Increases adenosine which slows immune system

- Shown to decrease appearance of new bone erosions

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20
Q

Drug shown to decrease appearance of new bone erosions?

A

Methotrexate

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21
Q

Side effects of Methotrexate?

A
  1. Hepatotoxicity: no alcohol
  2. Pulmonary toxicity
  3. Renal toxicity
  4. Marrow suppression
  5. Increased risk of lymphoma
  6. Teratogen
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22
Q

Metabolism of methotrexate?

A

90% renal excretion

- DO NOT USE IN PTN WITH COMPROMISED RENAL

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23
Q

Who is Methotrexate contraindicated in?

A
  1. Pregnancy/breast feeding: abortive agent
  2. Liver disease
  3. Renal disease
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24
Q

Indication of Leflunomide?

A
  • Alternative to those who are unable to take or are unresponsive to methotrexate
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25
Onset of Leflunomide?
1-2 months
26
What is Leflunomide a low cost alternative to?
- The TNF inhibitors | - Also is taken oral rather than IV which is added benefit
27
MOA of Leflunomide?
- Inhibits dihydroorotate dehydrogenase responsible for synthesis of Uridine - Arrests cell in G1 1. Inhibits T cell proliferation 2. Inhibits B cell production of Ig
28
Side effects of Leflunomide?
1. Htn: increased if using NSAIDS 2. GI / Rash 3. Hepatotoxicity: Increased with methotrexate - Monitor LFTs
29
What should not be taken with methotrexate?
Leflunomide: High rate of liver toxicity
30
Contraindications of Leflunomide?
1. Pregnancy | 2. Liver disease
31
Which drugs should not be taken in pregnancy?
1. Leflunomide | 2. Methotrexate
32
Importance of TNF alpha?
- Cytokine regulating inflammatory response - Made by CD4 T cells, macs, and masts * **Signals for the following pathways: 1. Bone resorption: osteoclasts 2. Cartilage breakdown: chondrocytes/synoviocytes 3. Joint inflammation: Leukocytes
33
What are the anti TNF alpha?
1. Adalimumab 2. Etanercept 3. Infliximab
34
MOA of anti TNFs?
- Bind to TNF alpha preventing it from binding to its receptor
35
Route of Anti TNFs?
- Subcutaneous or IV - Given weekly or b weekly -
36
Efficaciousness of anti TNFs?
As effective as methotrexate
37
Onset of AntiTNFs
- 1-4 weeks
38
Impact of Anti TNFs?
1. Decreased swelling and pain 2. Decrease new erosions 3. Decreased progression of structural damage
39
What are anti TNFs often used with?
Methotrexate if not responding to metho
40
Side effects of TNFs?
1. Increased opportunistic infections 2. Reactivate latent TB and HBV 3. Exacerbation of CHF 4. MS 5. Lymphoma 6. Sepsis: in acute / chronic infection
41
What to screen for before anti TNFs?
1. Latent TB infection | 2. Latent Hep B
42
What type of drugs is Adalimumab?
TNF alpha inhibitor
43
What type of drugs is Etanercept?
TNF alpha inhibitor
44
What type of drugs is Infliximab?
TNF alpha inhibitor
45
Which drug is a T cell inhibitor?
Abatacept
46
Which drug is a B cell inhibitor?
Rituximab
47
Which drug is an IL6 inhibitor?
Tocilizumab
48
Which drug is an IL1 inhibitor?
Anakinra
49
What type of drug is Abatacept?
T cell inhibitor
50
What type of drug is Rituximab?
B cell inhibitor
51
What type of drug is Tocilizumab?
IL 6 inhibitor
52
What type of drug is Anakinra?
IL 1 Inhibitor
53
MOA of Abatacept?
T cell inhibition via blocking CD28 stimulation
54
Who is Abatacept particularly effective in?
Patients unresponsive to TNF alpha inhibitors
55
Adverse effects of Abatacept? What to not give with?
1. Reactivation of TB / HBV | * ***Do not give with TNF alpha blockers
56
MOA of Rituximab?
Binds to CD20 on B cells depleting them from body
57
Onset of Rituximab?
3 months but 1 injection can last 6 - 24 months
58
Which drug has longest course of action after it is administered?
Rituximab
59
Adverse effects of Rituximab?
1. PML: "Progressive multifocal leukoencephalopathy" - fatal demyelination 2. Increased infection 3. Reactivation of latent infections
60
Drug known to cause PML?
Rituximab
61
MOA of Anakinra?
IL 1 Receptor antagonist
62
Route of anakinra?
Sub q once daily: 4 - 6 hour half life
63
Adverse effect of anakinra?
1. Neutropenia | 2. Same as others
64
Drug causing neutropenia?
Anakinra
65
What should not be combined with biologiques?
- Other Biologiques | - Can be used with DMARDs, however
66
Side effects of Tocilizumab?
1. Bone marrow suppression 2. Hepatotoxicity: Monitor LFTs 3. Increased cholesterol 4. Cancer 5. Infections
67
Which drug inhibits cytokine signalling?
Tofacitinib: Inhibits JAK tyrosine kinases
68
MOA of Tofacitinib?
Inhibits cytokine signalling via JAKs
69
Toxicity of Tofacitinib?
1. Marrow suppression 2. Hepatotoxicity: increased cholesterol 3. Increased infections
70
Alternative to methotrexate as disease progresses?
Leflunomide, progressing to biologique
71
What is gout linked to?
1. Purine rich diet: meat, booze 2. Metabolic syndromes 3. Overproduction or decreased excretion of uric acid * **Usually decreased excretion
72
Where does gout usually first present?
In the big toe
73
What are tophi?
Urate crystal deposits around joint promoting inflammation and joint destruction
74
Drugs used for acute gout?
1. Chclocicine 2. NSAIDs * ***Also use during chronic treatment to prevent acute attack
75
Which drugs promote uric acid excretion
1. Uricosuric agents: probenecid
76
Which drugs inhibit uric acid synthesis?
1. Allopurinol | 2. Febuxostat
77
Which drugs directly degrade uric acid?
1. Pegloticase
78
Which pain relievers should not be used for gout?
1. Aspirin 2. Salicylates * *Will induce gout at low doses but not at high
79
What is Chclocicine?
- Plant alkaloid preventing tubulin polymerization - Decreases leukocyte migration and phagocytosis - Anti Inflammatory with NO analgesics - Give in first 24 - 48 hours of attack
80
Side effects of Colchicine?
1. Nausea, vomiting, diarrhea | Therapeutic window is narrow and overlaps with side effects
81
MOA of probenecid?
- Inhibits anion transport in prox tubule | - Increased uric acid excretion
82
When do give chronic gout drugs?
- Not within 3 weeks of actual attack - Can initiate or prolong symptoms * **Prophylaxis with NSAID to decrease this risk
83
Contraindications of probenecid?
1. Uric acid overproduction: kidney stones 2. Renal insufficiency 3. Kidney stones
84
MAO of allopurinol and febuxostat?
- Inhibition of xanthine oxidase | - Xanthine oxidase catalyzes final two steps in purine degradation
85
Who are allopurinol and febuxostat best in?
1. High level of endogenous level of uric acid 2. Recurrent kidney stones 3. Presence of tophi
86
Side effects of allopurinol and febuxostat?
1. Allopurinol hypersensitivity: deadly - Renal disease, high dose, asians more likely * **Febuxostat does not cause this 2. Thrombocytopenia
87
DDI of allopurinol and febuxostat?
6-mercaptopurine and azathioprine (prodrug)
88
Treatment goal of gout?
Serum uric acid
89
Drug to use in overproduction?
Allopurinol
90
Drug to use in undersecretion?
Probenecid
91
Allopurinol indications?
1. Tophi 2. Renal failure 3. Kidnestones
92
Administration of Pegloticase?
- IV infusion every 2 weeks | - Effective more rapidly than others

Pharm: Psych (7 decks)

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