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LOCO 2 > Treatment of rheumatoid athritis > Flashcards

Treatment of rheumatoid athritis Flashcards

1
Q

As well as the joints, what does RA affect

A

Tendon sheaths

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2
Q

Is it symmetrical or asymmetrical

A

Symmetrical

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3
Q

What criteria is used to diagnose rheumatoid athritis

A

ACR/EULAR criteria

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4
Q

3 types of drugs used to manage rheumatoid athritis

A
  • Pain relief drugs
  • Drugs to modify disease progression
  • Adjunct therapy
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5
Q

What drug type can be used to manage rheumatoid athritis

A

Disease modifying anti-rheumatics (DMARDS)

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6
Q

What adjunct therapy can be used for RA

A

Oral corticosteroid pulse

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7
Q

When are DMARDS usually prescribed

A

In newly diagnosed rheumatoid athritis

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8
Q

What drugs specifically should be prescribed if DMARDs are being given in a combination

A

Methotrexate
+ one other DMARD
+ short term glucocorticoid

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9
Q

When may combination therapy not be appropriate

A

Comorbities or pregnancies

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10
Q

What should be done if recent onset RA is being treated with combination DMARD and things seem to be ok

A

Cautiously reduce dosage

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11
Q

What drug is first choice in rheumatoid athritis

A

Methotrexate

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12
Q

How is methotrexate administered normally

A

Orally once a week on the same day
2.5mg tablets.
Dosage from 5-10mg a week

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13
Q

How should methotrexate be adminstered if oral form doesn’t work

A

Subcutaneous or IM injection

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14
Q

How many weeks pass before benefit of using methotrexate is seen

A

3-12 weeks

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15
Q

What side effects may be experienced with methotrexate (5)

A

Liver problems
Can affect blood count
Folic acid antagonist so limits DNA/ RNA synthesis
Inhibits dihydrofolate reductase and thymidylate synthethase

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16
Q

How does methotrexate enter the cell

A

Reduced folate carrier using endocytic pathway activated by a folat ereceptor

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17
Q

What happens to methotrexate once it enters the cell (5)

A
  • Polyglutamated
  • Inhibits dihydrofolate reductase
  • Conversion of dihydrofolate to tetrahydrofolate is blocked
  • Tetrahydrofolate stores depleted reducing thymidylate synthesis
  • DNA and RNA synthesis blocked
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18
Q

What is sulfasalazine

A

Antibiotic that combines sulfapyridine and salicylate with azo bond

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19
Q

How is sulfasalazine administered

A

500mg daily orally, gradually increased over 4 weeks to 1g twice a day

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20
Q

How long must you take sulfasalazine before benefit is noticed

A

12 weeks

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21
Q

What are the disadvantages of sulfasalazine

A

Not well absorbed across the gut

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22
Q

Where in sulfasalazine concentrated

A

In connective tissue and serous fluid

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23
Q

What metabolises sulfasalazine

A

Gut bacteria

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24
Q

What does sulfasalazine break down into

A

5-aminosalicylic acid

Sulfapyridine

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25
Describe how sulfapyridine interacts with each part of the body
Absorbed rapidly in colon Aceylated in the liver Excreted in the urine
26
Does sulfapyridine have therapeutic action in ulcerative colitis
Nah
27
What is the effect of 5-ASA on ulcerative colitis and how does this work
Induces remission | Inhibits COX, LOX PAF, cytokines, IL-1 and TNF-alpha
28
What was hydroxychloroquine originally used to treat
Malaria
29
How is hydroxychloroquine administered
- oral with or after food - start 400mg daily - reduced to 2-3 times a week
30
Briefly describe the mechanism of action of hydroxychloroquine
- Accumulates in lysosomes increasing the pH decreasing protein modifications - Blocks T cell receptor 9 which recogises DNA containing immune complexes - Decreases dendritic cell activation
31
What drug is Leflunomide's efficacy most similar to
Methotrexate
32
What is the dosage of Leflunomide
10-20mg a day | 1st 3 days 100mg a day
33
What is the mechanism of action of leflunomide
Inhibits pyrimidine biosynthesis through inhibiting dihydroorotate dehydrogenase
34
How are gold salts administered
IM injections once a week-50mg
35
How long must you be taking gold salts before a change is noticed
4-6 months
36
How are biologicals generated
Genetic engineering
37
What do biologicals inhibit
- TNF-alpha - Interleukin 1 - B cells - T cell stimulation - IL-6 - IL-17 and 23
38
Give an example of a drug that blocks TNF-alpha (2)
Etanercept | Infliximab
39
What 2 molecules is etanercept a fusion of
human TNF receptor 2 | Fc human IgG1
40
How is etanercept administered
50mg once a week | Subcutaneous injection
41
Describe the time scale of etanercept
1-4 weeks for effect | Progressive improvement 3-6 months
42
What is infliximab
Monoclonal antibody against TNF-alpha | Antibody designed against mouse binding site of TNF-alpha with remaining 75% human IgG1
43
How is infliximab administered
3mg/kg influsions 2-3 hours in duration 2-6 weeks apart
44
Whata is adalimumab and what does it bind
Human TNF alpha monoclonal antibody | Binds TNF-alpha both soluble and bound
45
How is adalimumab administered
40mg subcutaneously every other week
46
Name 3 drugs that work against IL-1
Anakinra Canakinumab Rilonacept
47
What is anakinra
Human recombinant IL-1 receptor antagonist
48
Why is anakinra different from normal IL-1
Addition of n terminal methionine
49
At what dosage is anakinra prescribed
100mg per day | Subcutaneous
50
What is canakinumab
A human monoclonal antibody that target IL1B
51
What is rilonacept
Dimeric fusion protein extracellular domain of IL1R1 and human IgG1 Used for gout
52
Name a drug that works against B cells
Rituximab
53
What is rituximab
Chimeric monoclonal antibody against CD20 which is primarily found on B cells
54
What drug is rituximab given in combo with
Methotrexate
55
When is rituximab presribed
If patients fail to respond to one or more anti-TNFa agents
56
Name a drug that works against T cells
Abatacept
57
How does abatacept work
Prevents second signal from being delivered to T cell
58
Pros/ cons of abatacept
Similar clinical symptom improvement as TNFa inhib Slower onset Fewer adverse effects
59
What does Tocilizumab act again
IL-6
60
What drug should Tocilizumab be given in combo with
Methotrexate
61
Name 2 drugs that can be used in psoriasis. What antibodies do they go again
Secukinumab for IL 17 | Ustekinumab for IL 23
62
what is a neutralising anti drug antibody
Directly interferes with biological drugs ability to work
63
What is a non neutralising anti drug antibody
May form immune complexes around injection site reducing drug concentration and pharmacokinetics

LOCO 2 (25 decks)

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