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Pharmacology > Immunosupressants > Flashcards

Immunosupressants Flashcards

1
Q

Indications for corticosteroids?

A

Most autoimmune conditions however being in steroids long term has adverse effects. Example include polymyalgia rheumatica, arthritis, colitis, lupus psoriasis etc.

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2
Q

What are the adverse drug reactions of corticosteroids?

A

Weight gain, Immunosuppresion, cataracts, glaucoma, straie, avascular necrosis, glucose intolerance etc.

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3
Q

What is the mechanism of action of azathiopine?

A

Pro-drug. It is an anti-metabolite and decreases DNA and RNA synthesis. It is a nucleoside analogue and lymphocytes are predominately affected.
Steroid sparing drug.

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4
Q

What are the indications for azathioprine?

A

Maintenance therapy in - SLE and vasculitis

IBD, bullous skin disease, atopic dermatitis

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5
Q

What are the ADR’s of azathioprine?

A 
Bone marrow suppression 
Increased risk of malignancy 
Increased risk of infection 
Hepatitis 
Nausea and vomiting
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6
Q

Name an example of a calcineurin inhibitor?

A

Tacrolimus

Ciclosporin

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7
Q

What is the mechanism of action of calcineurin inhibitors?

A

Diffuses into T cells and binds to cyclophillin. This inhibits the synthesis of many cytokines including interleukin 2 which prevents activation of T helper cells.

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8
Q

What are calcineurin inhibitors indicated in?

A

Transplant medication
Atopic dermatitis
Psoriasis
Weak evidence of efficacy in RA

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9
Q

What ADRs are seen in calcineurin inhibitors?

A 
Nephrotoxicty 
Hypertension
Hyperlipidaemia 
Nausea, vomiting, diarrhoea 
Hyperuricaemia 
Need to monitor for toxicity.
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10
Q

What is the mechanism of action of mycophenolate mofetil (MMF)?

A

It is a prodrug which is converted to mycophenolic acid. Mycophenolic acid inhibits the enzyme required for guanosine synthesis. This impairs B and T cell proliferation.

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11
Q

What are the indications for mycophenolate mofetil?

A

Transplants

Lupus

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12
Q

What are the ADRs for mycophenolate mofetil?

A 
Myelosuppression
Nausea 
Vomiting 
Diarrhoea 
Metallic taste 
Abdominal pain
Leukopenia 
Anaemia
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13
Q

What is sulfasalazine a combination of?

A

Sulfapyridine

Mesalazine

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14
Q

What is the action of corticosteroids?

A

They act on nuclear receptors to decrease gene expression of inflammatory markers. Specifically interleukin 1,6 release by macrophages.

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15
Q

What are the indications for sulfasalazine?

A

IBS - mesalazine is not well absorbed and so stays in the gut.

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16
Q

What are some of the ADR’s of sulfasalazine?

A

Myelosupression
Hepatitis
Rash
Avoid in aspirin allergy

17
Q

What is the mechanism of action of sulfasalazine?

A

Inhibits T cell proliferation - May cause apoptosis
It inhibits Interleukin 2 production.
It also reduces chemotaxis and degranulation of neutrophils.

18
Q

What is the mechanism of action of Anti-TNF agents?

A

Monoclonal antibodies which block TNF-alpha which reduces inflammation by preventing recruitment of leukocytes to the site.
It also helps to reduce angiogenesis.
Decreased joint destruction.

19
Q

What are the indications of anti-TNF-alpha?

A

It is very expensive so only prescribed if other DMARDS have been ineffective.

20
Q

Give some examples of anti-TNF agents:

A

Infliximab
Eternercept
Adalimumab

21
Q

What are some of the ADR’s of anti-TNF agents?

A

Malignancy in those with past malignancy
Reactivation of TB
Increased infection risk
Increase skin and soft tissue infections.

22
Q

What is the mechanism of action of cyclophosphamide?

A

An alkylating agent that causes cross links in DNA which means that cells cannot replicate. This especially effects T and B cell activity.

23
Q

What are some of the ADRs with cyclophosphamide?

A

Increases risk of bladder cancer, lymphoma, leukaemia.

Infertility

24
Q

What are the indications for cyclophosphamide?

A

Wegners
Leukaemia
Lupus
Polyarteritis nodosa

25
Q

What monitoring is required with cyclophosphamide?

A

FBCs

Dose for renal impairment

26
Q

What are the mechanisms of action of methotrexate?

A

Reversible competitive inhibitor of Dihydrofolate redcuctase.
This causes a reduction in the production in folic acid.
Cytotoxic to cells in s phase of cell cycle. Therefore has a greater effect on rapidly dividing cells.
Prevents DNA and RNA synthesis

27
Q

What are the indications for methotrexate?

A

High dose - malignancy

Low dose and folic acid supplement - RA, SLE, vasculitis, Crohns.

28
Q

What are some of the ADRs of methotrexate?

A 
Requires toxic monitoring - steroid sparing. 
NSAIDS displace them. 
Mucositis 
Myelosupression - can be prevented by folic acid supplementation
Hepatitis 
Rash 
Pneumonitis 
Infection risk 
Highly teratogenic and abortifacient.
29
Q

What monitoring is required in methotrexate?

A

CXR
Baseline - FBC, LFT’s, U+Es
Creatinine
Regular monthly repeats.

30
Q

What is the mechanism of action of Rituximab?

A

Monoclonal antibody against B cells and plasma cells. - but not stem cells.
This helps to activate B cell lysis.

31
Q

What are the ADRs associated with Rituximab?

A

Hypogammaglobulinaemia
Increased risk of infection
Development of hypersensitivity reactions.

32
Q

What are the indications for Rituximab?

A

Non Hodgkin’s lymphoma
Lymphoma
Chronic lymphocytic leukaemia
In combination with methotrexate in severe RA

Pharmacology (8 decks)

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