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MSK > DMARDs, Biological Tharapies, Steroids > Flashcards

DMARDs, Biological Tharapies, Steroids Flashcards

1
Q

How are DMARDs broadly classified?

A

affect the disease process

affect the immine system

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2
Q

give examples of DMARDs that affect the disease process

A

gold
penicillamine
sulfasalazine

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3
Q

give examples of DMARDs that affect the immune system

A 
methotrexate
hydroxychloroquine
ciclosporin
azathioprine
leflunomide
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4
Q

what is sulfasalazine used for?

A

RA
psoriatic arthritis
IBD (most activity is in the bowel as it is poorly absorbed)

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5
Q

what is the active metabolite of sulfasalazine?

A

5-ASA

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6
Q

what are the ADRs of sulfasalazine?

A

agranulocytosis
thrombocytopaenia
hepatitis

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7
Q

what tpe of drug is methotrexate?

A

antimetabolite and antifolate

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8
Q

what are some contraindications to using methotrexate

A

PREGNANACY
liver impairment
immunosuppressed
active infection

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9
Q

what are the side effects of methotrexate?

A 
myelosuppression
liver toxicity
pulmonary toxicity
ulcerative stomatitis
very very teratogenic!!! (use to induce abortion, and antifolate)
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10
Q

what is methotrexate used to treat?

A

RA
psoriatic arthritis
SLE
cancer

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11
Q

what adive should you give to patients regarding diet and methotrexate?

A

take folate supplements

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12
Q

what type of drug is hydroxychloroquine?

A

antimalarial

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13
Q

what are the side effects of hydroxychloroquine?

A

retinopathy

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14
Q

what is hydroxychloroquine used to treat?

A

RA
SLE
good for photosensitive skin problems associated with autoimmune diseases
juvenile arthritis

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15
Q

what is azathioprine used to treat?

A 
SLE
vasculitis
IBD 
(RA)
cancer
transplants
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16
Q

how does azathioprine work?

A

metabolised to 6 mercaptopurine

antimetabolite that decreases DNA and RNA synthesis

17
Q

what must you check before initiating azathioprine therapy?

A

TPMT levels

18
Q

explain why TPMT deficiency is bad

A

TPMT converts 6-MP to inactive analogues

deficiency of TPMT means more 6-MP builds up and is converted by HGPRT pathway to cytotoxic analogues =(

19
Q

what are the warning symptoms you should advise patients to seek healthcare about if they get them while on DMARDs?

A
  • Sore throat
  • Fever and other signs of infection
  • Unexpected bleeding or bruising
  • Purpura and rashes
  • Mouth ulcers
  • Cough or breathlessness
20
Q

give examples of TNF-alpha inhibitors

A

infliximab
etanercept
adalimumab

21
Q

give some advantages of monoclonal antibodies compared to DMARDs

A

faster onset of action
LESS sides effects
no need for regular blood tests for monitoring

22
Q

when would you consider starting a biological therapy in a patient with RA?

A

when in addition to low dose steroids, 2 trials of six months of traditional DMARD monotherapy or combination therapy (at least one including methotrexate) should fail to control symptoms or prevent disease progression

23
Q

what type of drug is rituximab?

A

anti-CD20

24
Q

what are some side effects of monoclonal antibodies?

A 
immunosuppresion
reactivation of TB
reactivation of hepatitis B
lymphoma
drug-induced lupus
25
Q

how do steroids exert an immunosuppresive effect?

A

inhibit all stages of T cell activation

26
Q

how do steroids exert their anti-inflammatory effect?

A

prevent IL-1 and IL-6 production from macrophages

27
Q

name the general side effects of all immunosuppresants

A

myelosuppression
risk of malignancy
risk of infection

28
Q

name 2 calcineurin inhibitors.

what is their mechanism of action?

A

tacrolimus
ciclosporin
inhibit IL-2 production in T cells via calcineurin inhibition.

29
Q

what is one advantage of ciclosporin over the other immunisuppresants?

A

it doesn’t affect bone marrow

so useful in treating RA/SLE patients with cytopaenias (however it has other ADRs)

30
Q

what are the sides effects of calcineurin inhibitors?

A

nephrotoxicity
hypertension
hyperlipidaemia
hyperuricaemia

31
Q

how does mycophenolate mofetil work?

A

inhibits guanosine synthesis which is needed for B and T cell proliferation

32
Q

what is mycophenolate mofetil used for?

A

mainly transplants

also lupus nephritis

33
Q

how does methotrexate work?

A

inhibits dihydrofolate reductase
DHFR catalyses dihydrofolate to tetrahydrofolate which is needed in purine and thymidine synthesis
so methotrexate inhibits DNA, RNA and protein synthesis

34
Q

what phase of the cell cycle does methotrexate affect what what does this mean clinically?

A

S phase
so it is effective on rapidly dividing cells
therefore clinically it is best for malignant cells and GI/oral mucosa cells

35
Q

how and why is the dosing different for methotrexate?

A

weekly dosing

metabolites have long half lives

36
Q

what tests would you use to monitor methotrexate toxicity?

A

monthly FBc, LFT, U&E

baseline CXR

37
Q

how does sulfasalazine work?

A

inhibition of T cell proliferation and IL-2 production

reduced neutrophil chemotaxis and degranulation

MSK (6 decks)

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