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CPT > Immunosuppression + disease modifying therapy > Flashcards

Immunosuppression + disease modifying therapy Flashcards

1
Q

Describe rheumatoid arthritis
How does it occur?

A
  • autoimmune multi system disease
  • autoantibodies attack synovium
  • inflammatory change + proliferation of synovium (pannus) > dissolution of cartilage and bone
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2
Q

Clinical features of rheumatoid arthritis

A
  • morning stiffness >1 hour
  • arthritis of 3> joints
  • arthritis of hand joints
  • symmetrical arthritis
  • rheumatoid nodules
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3
Q

Non clinical features of rheumatoid arthritis

A
  • Serum rheumatoid factor/anti CCP antibodies
  • X ray changes LESS
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4
Q

Aims of rheumatoid arthritis treatment

A

Symptomatic relief
Prevention of joint destruction

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5
Q

What pro inflammatory markers are involved in rheumatoid arthritis?

A

IL1
IL6
TNF-a

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6
Q

Treatment strategy of rheumatoid arthritis

A
  • early use of disease modifying drugs to prevent progression
  • aim to achieve good disease control
  • use of adequate dosage + combination of drugs
  • avoidance of long term corticosteroids
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7
Q

What type of drug is avoided in long term treatment of rheumatoid arthritis?

A

Corticosteroids

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8
Q

Treatment goals of systemic lupus erythematous + vasculitis

A
  • symptomatic relief
  • reduction in mortality
  • prevention of organ damage
  • reduction in long term morbidity
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9
Q

Examples of anti-proliferative drugs

A

Azathioprine
Mycophenolate mofetil
Cyclophosphamide

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10
Q

What class of drug is azathioprine?

A

Anti-proliferative immunosuppressant

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11
Q

What are the uses of azathioprine?

A
  • systemic lupus erthymatous + vasculitis
  • IBS
  • rheumatoid arthritis (weakly)
  • atopic dermatitis
  • bullous skin disease
  • steroid ‘sparing’ drug
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12
Q

What is the mechanism of action of azathioprine?

A

Inhibition of synthesis of purines needed for DNA + RNA transcription

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13
Q

What are adverse drug reactions of azathioprine?

A

Immunosuppression
- risk of malignancy
- hepatitis
- infection risk
- bone marrow suppression

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14
Q

Examples of calcineruin inhibitiors

A

Ciclosporin
Tacrolimus

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15
Q

What is the mechanism of action of calcineurin inhibitors?
Two examples + how they differ

A
  • ciclosporin binds to cyclophilin protein
  • tacrolimus binds to tacrolimus binding protein
  • drug/protein complexes bind to calcineruin + cause inhibition
  • reduces helper T cell activity
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16
Q

What are the uses of calcineurin inhibitors?

A

Transplantation
Atopic dermatitis
Psoriasis

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17
Q

What are adverse drug reactions of calcineruin inhibitors?

A

Renal toxicity

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18
Q

What are important drug drug interactions of calcineurin inhibitors?

A
  • CYP inducers e.g. antivirals + antifungals
  • CYP inhibitors e.g.omeprazole, carbamazepine
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19
Q

What is the mechanism of action of ciclosporin?

A

Calcineurin inhibitor
- Binds to cylophilin protein
- Drug/protein complex bind calcineurin + prevents it’s action > prevents production of IL-2 + T helper cell activity

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20
Q

What is the mechanism of action tacrolimus?

A

Calcineurin inhibitor
- binds to tacrolimus-binding protein
- drug/protein complex binds to calcineruin + inhibits its action > prevents production of IL-2 + T helper cell activity

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21
Q

What class of drug is mycophenolate mofetil?

A

Anti-proliferative immunosuppressant

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22
Q

What are the uses of mycophenolate mofetil?

A

Transplantation
Induction + maintenance therapy for lupus nephritis
Maintenance of vasculitis

23
Q

What is the mechanism of action of mycophenolate mofetil?

A
  • prodrug
  • inhibitors inosine monophosphate dehydrogenase (needed for guanosine synthesis)
  • impairs B+T cell proliferation
24
Q

Why does mycophenolate mofetil impair B+T cell proliferation but spare other rapidly dividing cells?

A

Other cells have guanosine salvage pathways

25
Q

What are adverse drug reactions of mycophenolate mofetil?

A

N+V
diarrhoea
Myelosuppresion (bone marrow)

26
Q

What class of drug is cyclophosphamide?

A

Anti-proliferative immunosuppressant

27
Q

What are the uses of cyclophosphamide?

A
  • Lymphoma, leukaemia, solid cancers
  • lupus nephritis
  • Wegener’s granulomatosis
28
Q

What is the mechanism of action of cyclophosphamide?

A
  • Prodrug: converted in liver to active form by CYP450
  • inhibtis B+T cell proliferation
29
Q

What are adverse drug reactions of cyclophosphamide?

A
  • increased risk of bladder cancer, lymphoma + leukaemia
  • infertility
  • monitor RBC
30
Q

Examples of DMARDs (disease modifying anti rheumatic drugs)

A

Methotrexate
Sulfasalazine
Mesalazine
Hydroxychloroquine
Rituximab

31
Q

What should be monitored whilst a patient is taking cyclophosphamide?

A

FBC

32
Q

What class of drug is methotrexate?

A

Disease modifying anti-rheumatoid drug
DMARD

33
Q

What are the uses of methotrexate?

A

RA
Malignancy
Psoriasis
Crohn’s disease

34
Q

What is the mechanism of action of methotrexate in malignancy?

A
  • Competitively + reversible inhibtis dihydrofolate reductase
  • inhibtis dihydrofolate > tetrahydrofolate needed in purine + pyrimidine synthesis
  • therefore, inhibits DNA, RNA + protein synthesis
35
Q

What is the mechanism of action of methotrexate in non malignant disease e.g. RA?

A
  • NOT via anti-folate action
  • inhibition of accumulation of adenosine
  • inhibits T cell activation
  • suppression of intracellular adhesion molecule expression by T cells
36
Q

What are adverse drug reactions of methotrexate?

A
  • mucositis
  • bone marrow suppression
  • hepatitis + cirrhosis
  • pneumonitis
  • infection risk
  • highly teratogenic
37
Q

How can some of methotrexate ADRs be treated?

A

Bone marrow suppression + mucositis both respond to folic acid supplementation

38
Q

What class of drug is sulfasalazine?

A

Disease modifying anti-rheumatic drug
DMARD

39
Q

What are the uses of sulfasalazine?

A

RA
IBD

40
Q

What is the mechanism of action of sulfasalazine?

A

5-aminosalicylic acid donor in RA > immunosuppression + anti inflammatory effec

41
Q

What are the adverse drug reactions of sulfasalazine?

A
  • myelosuppression
  • hepatitis
  • rash
  • N+V
  • abdominal pain
42
Q

What DMARD should be avoided in pregnancy?

A

Methotrexate

43
Q

What is the mechanism of action of ‘biologicals’/MAB?

A
  • TNF-a inhibiton
  • reduces inflammation, angiogenesis + joint destruction
44
Q

What are adverse drug reactions of biologicals/MAB?

A

Risk of TB reactivation > screen for latent TB before anti-TNF treatment

45
Q

What class of drug is rituximab?

A

‘Biologicals’
Monoclonal antibody

46
Q

What is the mechanism of action of rituximab?

A

Binds to CD20 on specific B cells > B cell apoptosis

47
Q

What are uses of rituximab?

A

RA

48
Q

Examples of systemic corticosteroids

A

Hydrocortisone
Prednisolone
Betamethasone
Dexamethasone

49
Q

What are uses of systemic corticosteroids?

A

Perioperative N+V
Chemotherapy
Palliation

50
Q

What is the mechanism of action of systemic corticosteroids?

A
  • prevents IL1+6 production by macrophages
  • inhibits all stage of T cell activation
51
Q

What are adverse drug reactions of corticosteroids?

A

Insomnia
Increased appetite
Increased blood sugar

52
Q

What should be tested for before prescribing azathioprine and why?

A
  • TPMT activity
  • involved in metabolism of azathioprine
  • TPMT gene is highly polymorphic
  • low/absent TPMT level increases risk of myelosuprresion
53
Q

Relationship between TPMT activity and myelosuppresion risk

A

Low/absent TPMT activity = risk of myelosuppresion

CPT (28 decks)

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