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Locomotor Y2 > Treatment options for Rhumatoid arthritis > Flashcards

Treatment options for Rhumatoid arthritis Flashcards

1
Q

Describe the

A

Joint involvement Score

1 large joint 0

2-10 large joints 1

1-3 small joints 2

4-10 small joints 3

>10 joints (at least 1 small joint) 5

Serology

Negative RF and negative ACPA 0

Low positive RF or low positive ACPA 2

High positive RF or high positive ACPA 3

Acute phase reactants

Normal CRP and normal ESR 0

Abnormal CRP or abnormal ESR 1

Duration of symptoms

<6 weeks 0

>6 weeks 1

> 6/10 for diagnosis

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2
Q

What is the order of RA treatment based on severity

A

Newly diagosed- Pain managment

NSAIDS,COX- 2 inhibitors, Narcotics (opioids)

First line treatment (Mild Ra)

Methotrexate + second line DMARD

Second line treatment (moderate RA)

Methotrexate + TNF alpha inhibitors

Second line teratment (sever RA)

Methotrexate and Rituxximab

For unmanageable RA

Surgival intervention

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3
Q

List 4 non-pharmacological treatments for RA

A
  • Physiotherapy
  • Occupational therapy
  • Podiatry
  • Therapy (for relaxation, stress managment and coping)
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4
Q

What is the Adjunct therapy used to treat RA that is not on the usual treatment schedual?

A

Oral corticosteroid pulse

Prednisone

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5
Q

When someone is newly diagnosed with RA, how would you treat them?

A

•Methotrexate and at least one other DMARD plus short term glucocorticoids

When control is obtained, reduce the dose to a level that still controls the disease

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6
Q

What is the treatment stratergy used when combination DMARD therapy is not appropriate?

A

•DMARD monotherapy

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7
Q

How is Methotrexate administerd and what is the starting dose?

A

•Orally once a week on the same day

–2.5mg tablets

–Start between 5-10mg a week

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8
Q

What is the alternative mode of administartion used when oral methotrexate doesnt work?

A

subcutaneous or intramuscular injection of methotrexate

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9
Q

How long does it take for the benifits of methotrexate to start working?

A

3-12 weeks

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10
Q

List 3 side effects of methotrexate

A

–Can cause liver problems- hepatotoxicity with fibrosis and cirrhosis

–Can affect blood count- cytopenia useually leukopenia and thrombocytopenia - due to bone marrow surpression

  • Stomatitis
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11
Q

What is the mode of action for methotrexate?

A
  • Folic acid antagonist
  • It limits DNA and RNA synthesis
  • Inhibits dihydrofolate reductase and thymidylate synthetase
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12
Q

How does methotrexate enter the body? What is it converted into when it enters the body?

A

Enters via acive transport using folate receptors/ carriers

It is converted into methotrexate glutamate

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13
Q

What is Sulfasalazine composed of?

A

–Combines sulfapyridine and salicylate with azo bond

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14
Q

How is Sulfasalazine normally administerd?

A

Orally-

Satrts with 500mg daily

–Gradually increased over 4 weeks

1g twice a day

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15
Q

How long does it take for the effects of Sulfasalazine to present?

A

12 weeks

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16
Q

How does Sulfasalazine enter the blood stream?

A

Not well absorbed across the gut. Metabolised by gut bacteria and these are better absorbed

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17
Q

What is the effect of Sulfasalazine on RA?

A

Mode of action is not well understood

Gets concentrated in connective tissue and serous fluids

relieves arthritic symptoms

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18
Q

Which other condition does Sulfasalazine treat?

A

ulcerative colitis

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19
Q

When Sulfasalazine is absorbed it is broken down into 2 things. Name then and state which of the two has the theraputic effect?

A

Sulfapyridine and 5-ASA = 5-aminosalicylic acid

5-ASA = 5-aminosalicylic acid- inhibits COX, IL-1 and TNF alpha

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20
Q

When Sulfasalazine enters the liver, what is it converted into?

A

NAT2 = N-actetyltransferase 2

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21
Q
A
22
Q

What kind of drug is Sulfasalazine?

A

An antibiotic

23
Q

What type of drug is Hydroxychloroquine?

A

Anti-malarial drug

24
Q

How is Hydroxychloroquine administerd?

A

•Oral with or after food

–Start

•400mg daily

–Reduced to 2-3 times a week

25
Q

What is the mechanism of action for Hydroxychloroquine?

A
  • Accumulates in lysosomes increasing the pH decreasing protein modifications
  • Blocks Toll-like receptor 9 which decreases activation of dendritic cells
26
Q

The efficacy of Leflunomide is similar to another drug, name this drug

A

methotrexate

27
Q

How much Leflunomide should be given a day?

A

For the first 3 days - a higher dose 100mg a day

then 10-20mg a day

28
Q

What is the mode of action for Leflunomide?

A

–Inhibits pyrimidine Synthesis by inhibiting dihydroorotate dehydrogenase (DHODH)

29
Q

What is the emchanism of action for D-Pencillamine?

A

–Copper chelator

–Thought to decrease immune response and IL1 generation

–Preventing maturation of newly synthesised collagen prevents collagen cross linking (prevent fibrosis)

30
Q

What are the side effects of D-Pencillamine?

How is this potenial side effect monitored?

A

–Kidney damage – monitor for proteinuria

31
Q

How are Gold Salts administerd?

A

Intra muscular injections given once a week

32
Q

What is the avergae dosage for Gold salts?

A

50 mg

33
Q

How long does it take for the effects of Gold salts to be seen?

A

4-6 months

34
Q

What is the mode of action for Gold salts?

A

alter morphology and function of macrophages and inhibits monocyte chemotactic factors IL-8, 1beta

Reduce histamine release

Affects lysosomal activity

35
Q

Biological DMARDS have 6 main fucntions, name them

A

–inhibition of TNFα

–inhibition of interleukin 1

–Inhibit B cells

–Block T-cell stimulation

–Inhibition of interleukin 6

–Inhibition interleukin 17 and 23

36
Q

Give 3 examples of a TNF alpha inhibitor?

A

•Etanercept

Recombinant TNF receptor: Fc fusion protein

•Infliximab

–Monoclonal antibody against TNFα

•Adalimumab

–Human TNFα monoclonal antibody

37
Q

What is the dosage and administration for Etanercept?

A

–50mg once per week subcutaneous injection

38
Q

How long does it take for Etanercept to take effect?

A

–1-4 weeks for effect

39
Q

How is Infliximab administerd? How long does it take to have an effect?

A

3mg/kg Infusions 2-3 hrs in duration 2-6 weeks apart

–Days to weeks to have an effect

40
Q

How is Adalimumab administered? How long does it take to have an effect?

A

–40mg subcutaneously every other week.

–Effect seen 1-4 weeks

41
Q

List and describe 3 drugs which inhibit interlukin 1

A

Anakinra- –Human recombinant IL-1 receptor antagonist

Canakinumab - Human monoclonal antibody targets IL1β

Rilonacept-

42
Q

How is Anakinra administerd? What is the usual dosage? And how long does it take to have an effect?

A

–100mg per day subcutaneous

–2-4 weeks to have an effect

43
Q

Name and describe 1 drug which inhibits B cells

A

•Rituximab

–Chimeric monoclonal antibody against CD20 primarily found on surface of B-cells

44
Q

Name and describe 2 drugs which inhibits T cells

A

•Abatacept

–Fusion protein IgG fused to extracellular domain of CTLA-4

45
Q

How is Rituximab administerd? What is the usual dosage? How long does it take for the effects ot occure?

A

–A single course of 2 infusions of 1000mg given 2 weeks apart depletes B-cells for up to 6 months and possibly 1 year

46
Q

What is the mechanism of action for Abatacept

A

–Prevents 2nd signal (co-stimulatory) from being delivered to T-cell

47
Q

How is Abatacept adminaisterd? How long do the effects take to happen?

A

–Dosage dependent on body weight i.v. infusion over 30mins to 1hr once a month

48
Q

What os one positive and one negtiave aspect of Abatacept compared to TNFα agents

A

Positive- Fewer adverse events

Negative-

49
Q

Name and describe 1 drug which inhibits interlukin 6. What is its mechanism of action?

A

•Tocilizumab

–Humanized monoclonal antibody against membrane and soluble IL-6 receptor

50
Q

How is Tocilizumab administered?

A

–i.v. 8mg/kg monthly

51
Q

Name 1 drug which is an IL-23 inhibitor? What is this drug used to treat?

A

Ustekinumab

used in psoriasis

52
Q

What is a neutralising and Non-neutralising anti-drug antibody

A

Neutralising - Directly interferes with the biological drugs ability to work

Non neutralising -

May form immune complexes around injection site reducing drug concentration and pharmacokinetics

Increased clearance

Locomotor Y2 (8 decks)

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