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PHA223 > RA 2 - treatment (SD) > Flashcards

RA 2 - treatment (SD) Flashcards

1
Q

1st RA treatment

A

NSAIDs
immediate relief to pain
don’t alter LT progression

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2
Q

How do NSAIDs work?

A

through COX enzyme inhibition

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3
Q

adverse effects of NSAIDs

A

gastric
headache
hypertension

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4
Q

NSAID examples and doses (high doses)

A 
diclofenac 150mg max daily dose
etodolac 1200mg
fenoprofen 3200mg
flurbiprofen 300mg
ibuprofen 3200mg
indomethacin 200mg
naproxen 1500mg
celecoxib 400mg
piroxicam 20mg
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5
Q

2nd treatment for RA

A

DMARDs

disease modifying anti-rheumatic drugs

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6
Q

What do DMARDs do?

A

they slow the progression of RA

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7
Q

When do DMARDs have an effect?

A

take weeks/months to work

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8
Q

traditional DMARDs examples

A 
sulfasalazine
leflunomide
MTX
azathioprine
hydroxychloroquine
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9
Q

examples of biologic DMARDs

A 
rituximab
abatacept
tofacitinib
infliximab
tocilizumab
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10
Q

What are DMARDs used for (4 reasons in RA)?

A

decrease activated T cells
target macrophages
target cytokines
stop bone erosion

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11
Q

1st choice DMARD

A

aminosalicylate

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12
Q

What is aminosalicylate an analogue of?

A

salicylic acid

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13
Q

oral form of animosalicylate?

A

sulfasalizine (5ASA)

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14
Q

2 components of sulfasalazine

A

sulfapyridine

5-ASA (active component)

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15
Q

What links 5ASA and sulpapyridine in sulfasalazine?

A

a diazo bond

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16
Q

What cleaves the diazo bond in sulfasalazine?

A

colonic bacteria

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17
Q

How does 5ASA work?

A

inhibition of leukocyte movement
reduces cytokine levels and TNF
inhibition of inflammatory mediators

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18
Q

What inflammatory mediators does 5ASA inhibit?

A

prostaglandins
leukotrienes
platelet activating facor
cyclooxygenase

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19
Q

side effects of sulfapyridine

A

headache
dizziness
fever
allegic reaction

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20
Q

2 immunosuppressants - drug to suppress the immune system

A

methotrexate

leflunomide

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21
Q

What type of drug is methotrexate?

A

antifolate

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22
Q

When is methotrexate given?

A

in RA when intolerant/insufficient response to first line therpapy (aminosalycylate)

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23
Q

How does methotrexate work?

A
  • it blocks pyrimidine and purine bio synthetic pathway

- blocks proliferation of B-cells by interfering with DNA synthesis/repair/replication

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24
Q

What is leflunomide used for?

A 
prevents skin/heart/kidney graft rejection (animals)
autoimmune diseases (humans - RA/psoriatic arthritis)
25
Q

How does leflunomide work?

A
  • inhibits the pyrimide biosynthetic pathway
  • dec DNA/RNA nitrogen-containing bases
  • stops B /T cell proliferation cycles, production of antibodies
26
Q

What does leflunomide inhibit?

A

DHODH

dihydroorotate dehydrogenase

27
Q

What is leflunomide metabolised to? (active metabolite)

A

teriflunomide

28
Q

What does teriflunomide inhibit?

A

DHODH - dihydroorotate dehydrogenase

29
Q

What does DHODH convert to?

A

orotic acid

this converts to uridine (uricil + ribose, uricil is a component of RNA)

30
Q

What happens when DHODH is blocked and pyrimide pools cannot form?

A

decreases DNA/RNA synthesis

inhibits lymphocyte proliferation

31
Q

What is hydroxychloroquine?

A

4-aminoquinoline

32
Q

What is hydroxychloroquine used to treat?

A

RA
lupus erythematous
malaria

33
Q

How does hydroxychloroquine work?

A

MA unknown but:
accumulates and stabilises lysosomes
impacts antigen presentation
causes suppression of T cells

34
Q

examples of biologic DMARDs

A 
rituximab
abatacept
tofacitinib
infliximab
tocilizumab
35
Q

What do biologic DMARDs centre around?

A

monoclonal antibodies

36
Q

suffix of biologic DMARDs

A

-mab (monoclonal antibody)

37
Q

anti-TNF biologic DMARDs

A 
adalimumab
certolizumab
etanercept
golimumab
infliximab
38
Q

anti- IL1 DMARD

A

anakinra

39
Q

anti-IL6 DMARD

A

tocilizumab

40
Q

What do TNF alpha biologics target?

A

TNF

TNFR (receptor)

41
Q

What are adalimumab and golimumab?

A

biologic DMARDs - TNF alpha

fully humanised monoclonal antibodies specific for TNF alpha

42
Q

What is certolizumab?

A

TNF alpha biologic DMARD

Fab fragment of a humanised monoclonal antibody specific for TNF alpha

43
Q

What is etanercept?

A

TNF alpha biologic DMARD
fusion protein consisting of 2 recombinant soluble extracellular portions of the human TNFR2
fused to the constant domain of human IgG1
binds to TNF alpha

44
Q

What is infliximab?

A

TNF aplha biologic DMARD
chimaeric monoclonal antibody
neutralises TNF aplha

45
Q

example of IL1 biologic DMARD

A

anakinra

46
Q

How does Anakinra work?

A

competitively inhibits IL-1 binding to the IL-1 type 1 recepor

47
Q

What does IL-1 cause?

A

imflammation

immunological response

48
Q

example of IL6 biologic DMARD

A

tocilizumab

49
Q

What is tocilizumab?

A

recombinant humanised monoclonal antibody

acts as a competitive inhibitor at the IL-6 receptor

50
Q

What is IL-6?

A

proinflammatory cytokine produced by T and B lymphocytes, monocytes and fibroblasts

51
Q

example of a T-cell co-stimulation modulator

A

Abatacept

52
Q

What do T-cell co-stimulation modulators do?

A

prevent T cell activation

53
Q

What does the ‘co-stimulatory signal’ involve?

A

binding of CD80/CD86 molecules on the surface of APC to the CD28 receptor on T-cells

54
Q

How does abatacept work?

A

it selectively binds to CD80/CD86 and blocks the co-stimulatory signal

55
Q

How is abatacept given?

A

IV infusion

56
Q

half life of abatacept

A

long, 14 days

57
Q

example of an anti-CD20 B-cell depleter

A

Rituximab

58
Q

What is CD20?

A

a cell marker on B cells

59
Q

How does rituximab work (anti-CD20 B cell depleter)?

A

depletes CD20+ B cells by bining to the CD20 antigen expressed on the cells surface
blocking CD20 leads to B cell death via apoptosis/lysis

PHA223 (43 decks)

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