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Clinical Pharmacology > 11) Immunosuppression and Rheumatology > Flashcards

11) Immunosuppression and Rheumatology Flashcards

1
Q

Describe rheumatoid arthritis:

A

Autoimmune multi-system disease initially localised to synovium

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2
Q

What is the pathogenesis of rheumatoid arthritis due to?

A

Imbalance between pro and anti-inflammatory molecules

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3
Q

How is rheumatoid arthritis diagnosed?

A

Morning stiffness > 1 hour
Arthritis in 3 or more joints
Arthritis in hand joints
Symmetrical arthritis

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4
Q

What are the treatment goals in RA?

A

Symptomatic relief and prevention of joint destruction

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5
Q

What is SLE?

A

Autoimmune disease causing inflammation of various parts of the body

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6
Q

What is vasculitis?

A

Inflammation of blood vessels, can affect kidney, skin and lungs

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7
Q

What are the treatment goals in vasculitis?

A

Symptomatic relief
Reduction in morbidity and mortality
Prevention of organ damage

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8
Q

What is the mechanism of action of corticosteroids?

A

Bind to intracellular gluco-corticoid receptors and prevent IL-1 and IL-6 production by macrophages. Inhibit T cell activation

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9
Q

Give examples of immunosuppressants:

A 
Corticosteroids
Azathioprine
Ciclosporin
Tacrolimus
Mycophenolate mofetil
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10
Q

Give examples of disease modifying anti-rheumatic drugs (DMARDs):

A 
Methotrexate
Sulfasalazine
Anti-TNF alpha
Rituximab
Cyclophosphamide
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11
Q

When is azathioprine indicated?

A

SLE, vasculitis, IBD, transplantation, atopic dermatitis

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12
Q

What is the mechanism of action of azathioprine?

A

Inhibits purine metabolism (anti-metabolite)

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13
Q

What are the side effects of azathioprine?

A

Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
Hepatitis

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14
Q

When are calcineurin inhibtors (ciclosporin, tacrolimus) indicated?

A

Transplants, atopic dermatitis, psoriasis

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15
Q

What is the mechanism of action of calcineurin inhibitors?

A

Prevent production of IL-2 by T helper cells via calcineurin inhibition
Ciclosporin binds to cycophilin protein
Tacrolimus binds to tacrolimus binding protein

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16
Q

What are the side effects of calcineurin inhibitors?

A 
Renal toxicity
Drug interactions (CYP P450)
17
Q

When is mycophenolate mofetil indicated?

A

Transplantation, induction and maintenance of lupus

18
Q

What is the mechanism of action of mycophenolate mofetil?

A

Inhibits monophosphate dehydrogenase required for guanosine synthesis, impairing B and T cell proliferation

19
Q

What are the side effects of mycophenolate mofetil?

A 
Leucopenia and neutropenia
Myelosuppression
Nausea
Diarrhoea
GI ulcers
20
Q

When is cyclophosphamide indicated?

A

Lymphoma, leukemia, lupus, ANCA vasculitis

21
Q

What is the mechanism of action of cyclophosphamide?

A

Alkylating agents that cross links DNA so that it cannot replicate

22
Q

What are the side effects of cyclophosphamide?

A

Metabolite (acrolein) is toxic to bladder epithelium - haemorrhage cystitis
Risk of bladder cancer, lymphoma and leukemia
Infertility

23
Q

When is methotrexate indicated?

A

RA, malignancy, psoriasis, Crohn’s

24
Q

What is the mechanism of action of methotrexate (malignant)?

A

Inhibits dihydrofolate reductase to stop conversion of dihydrofolate to tetrahydrofolate used in purine and thymidine synthesis

25
Q

What is the mechanism of action of methotrexate (non-malignant)?

A

Inhibition of purine metabolism leading to accumulation of adenosine, inhibition of T cell activation

26
Q

How is methotrexate administered and how often?

A

IM or SC

Weekly dosing

27
Q

What are some side effects of methotrexate?

A 
Mucositis
Myelosuppression
Hepatitis
Cirrhosis
Pneumonitis
Teratogenic
28
Q

How is cyclophosphamide excreted and therefore what needs to be given alongside?

A

Excreted by kidneys but metabolite toxic to bladder epithelium so give aggresive hydration +/- mesna

29
Q

What drugs interact with methotrexate?

A

NSAIDs
Phenytoin
Tetracyclins
Penicillins

30
Q

When is sulfasalazine indicated?

A

RA, IBD (Crohn’s)

31
Q

What is the mechanism of action of sulfasalazine in RA?

A

Inhibits T cell proliferation, T cell apoptosis inducer and inhibits IL-2 production

32
Q

What is the mechanism of action of sulfasalazine in IBD?

A

In colon broken down to 5-ASA and sulfapyridine

5-ASA is poorly absorbed and affects gut flora

33
Q

What are some side effects of sulfasalazine?

A 
Myelosuppression
Hepatitis
Rash
Abdo pain
N&V
34
Q

What are the effects of anti-TNF alphas?

A

Decreased inflammation - down reg of cytokine cascade
Decreased angiogenesis
Decreased joint destruction

35
Q

What must be screened for before giving anti-TNFs?

A

Latent TB

36
Q

What is the mechanism of action of rituximab and when is it used?

A

Binds to CD20 on B cells, causes B cell apoptosis

RA, lupus, vasculitis

Clinical Pharmacology (24 decks)

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