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Pharm > Anti-rheumatoid drugs > Flashcards

Anti-rheumatoid drugs Flashcards

1
Q

Describe pathophysiology of RA

A

Either decrease of anti inflammatory or increase in pro inflammatory molecules
Leading to dissolution of articular cartilage and bone. Formation of a pannus (inflammatory cell infiltrate into synovium so fibrovascular layer over joint surface)

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2
Q

Clinical features of RA

A

Early morning stiffness (>1 hour)
Symmetrical pain and swelling of small joints (at least 3)
Rheumatoid nodules
Hand deformities

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3
Q

Immunosuppressants used to treat autoimmune disorders

A

Corticosteroids
Calcineurin inhibitors (tacrolimus and ciclosporin)
Azathioprine
Mycophenolate mofetil

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4
Q

Examples of DMARDs

A 
Methotrexate
Sulphasalazine
Anti-TNF
Rituximab
Cyclophosphamide
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5
Q

MoA of corticosteroids

A

Inhibit T cell activation

Inhibit IL1 and IL6 (proinflammatory)

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6
Q

Indications for azothioprine

A

SLE
IBD
Vasculitis

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7
Q

What needs to be done prior to starting azathioprine

A

Test TPMT activity (metabolises azathioprine)

If lower activity need lower dose

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8
Q

MoA of azathioprine

A

Steroid sparing drug

Cleaved to 6-MP which decreases DNA synthesis

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9
Q

Side effects of azathioprine and what needs to be monitored

A

Bone marrow suppression - need to monitor FBC
Malignancy and infection risk
Hepatitis - need to monitor LFTs

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10
Q

Indications for calcineurin inhibitors

A

Transplant
Atopic dermatitis
Psoriasis

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11
Q

MoA of calcineurin inhibitors

A

Ciclosporin binds to cyclophilin
Tacrolimus binds to tacrolimus binding protein
Complexes bind to calcineurin which prevents calcineurin from activating T cell to start IL2 transcription

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12
Q

Sided effects of calcineurin inhibitors and what needs monitoring

A

Nephrotoxic - monitor GFR and BP
Diarrhoea and vomiting
Hyperlipidaemia - monitor cholesterol

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13
Q

Indications for MM

A

Transplant

Lupus nephritis

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14
Q

MoA of MM

A

MPA (prodrug) inhibits inosine monophosphate dehydrogenase so prevents guanine synthesis
This impairs B and T cell proliferation

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15
Q

Indications for methotrexate

A

RA
Malignancy
Psoriasis
Crohn’s

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16
Q

Interactions of methotrexate

A

Highly protein bound so is displaced by NSAIDs

17
Q

Dose regimen of methotrexate

A

Weekly

18
Q

MoA of methotrexate in non-malignancy dose

A

Inhibits purine metabolism and increases adenosine which reduces T cell activation

19
Q

Contraindications for methotrexate

A

Chronic liver disease

Pregnancy

20
Q

MoA of methotrexate in malignancy dose

A

Inhibits DHFR so inhibits folate synthesis which is needed for DNA synthesis (S phase of cell cycle)
Has greater toxicity in rapidly dividing cells

21
Q

What needs to be done before starting methotrexate

A

LFTs
CXR
Pregnancy test if applicable

22
Q

Side effects of methotrexate

A 
Mucositis in malignancy dose
Bone marrow suppression 
Hepatitis
Cirrhosis
Pneumonitis
Infection risk
23
Q

Indications for sulphasalazine

A

RA

IBD

24
Q

What is contained in sulphasalazine and why does this make it good for treating IBD

A

5-ASA (active part)

Sulfapyridine (poorly absorbed by gut so drug stays at site of action)

25
Q

MoA of sulphasalazine

A

Inhibits T cell proliferation
Inhibits IL2 production
Reduces neutrophil degranulation

26
Q

Side effects of sulphasalazine

A 
Bone marrow suppression
Hepatitis
Rash
Abdominal pain 
Nausea 
(Side effects usually last <8 weeks)
27
Q

What needs to be done prior to starting anti-TNF therapy

A

Latent TB screen

28
Q

MoA of anti-TNF

A

anti inflammatory
Decreases angiogenesis
Inhibits metalloproteinases so slows joint destruction

29
Q

Indications for rituximab

A

RA mainly
SLE
Vasculitis

30
Q

MoA of rituximab

A

Monoclonal antibody which binds to CD20 causing B cell apoptosis

31
Q

Indications for cyclophosphamide

A

Leukaemia
Lymphomas
Lupus nephritis
ANCA vasculitis

32
Q

MoA of cyclophosphamide

A

Prodrug cleaved to 4-HC

Cross links DNA and suppresses B and T cell activity

33
Q

Side effects of cyclophosphamide

A

Bladder cancer
Lymphoma
Leukaemia
Infertility (proportional to dose and age)

34
Q

What should be done before starting pre menopausal women on cyclophosphamide

A

Freeze eggs

Infertility counselling

35
Q

How does cyclophosphamide affect the bladder and what can prevent this

A

Acrolein is a cyclophosphamide metabolite which is toxic to bladder epithelium and causes haemorrhagic cystitis
Prevent by high hydration and mesna (binds to acrolein)

Pharm (20 decks)

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