Immunosuppressants Flashcards

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1
Q

What are 2 treatment goals of Rheumatoid Arthritis?

A
  • Symptom relief

- Prevent joint destruction (Erosion can’t be reversed)

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2
Q

Describe the overall treatment strategy for RA

A
  • Early use of disease-modifying drugs
  • Use of adequate doses & combinations of drugs
  • Avoid long term corticosteroid use
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3
Q

Lupus is photosensitive. What organs can it affect?

A

All of them

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4
Q

How do Corticosteroids work as Immunosuppressants?

A
  • Prevent IL-1 and IL-6 production by macrophages

- Inhibit all stages of T cell activation

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5
Q

Name one of the ‘biological’ disease modifying anti-rheumatic drugs (DMARDs) that is used to treat RA, Lupus and Vasculitis

A

Rituximab (Causes B cell apoptosis)

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6
Q

Describe the use of Azathioprine in treating;

  • Lupus & Vasculitis
  • RA
  • IBD
A

L&V: Used as a maintenance therapy (not strong enough to induce remission)

RA: Shouldn’t be used for this, as no evidence that it works

IBD: Can be used

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7
Q

Describe the pharmacodynamics of Azathioprine and its clinical significance

A
  • Azathiopine’s active metabolite 6-MP is metabolised by the enzyme TPMT
  • TPMT is highly polymorphic
  • TPMT activity should be tested before prescribing (E.g trial dose of Azathioprine before prescription)
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8
Q

List 5 ADRs of Azathioprine

ALL Immunosuppressants have these ADRs

A
  • Bone marrow/ Myelosuppression (monitor FBC)
  • Increased risk of malignancy (especially transplant patients)
  • Mucositis
  • Increased risk of infection
  • Hepatitis (monitor LFT)
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9
Q

Ciclosporin and Tacrolimus are members of what drug class?

What are they used for?

A

Calcineurin inhibitors

  • Transplantation
  • Atopic dermatitis
  • Psoriasis
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10
Q

Why should BP and GFR be checked regularly in patients who are using Calcineurin Inhibitiors?

A

Can cause renal toxicity

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11
Q

How do Calcineurin Inhibitiors interact with CYP 450 enzymes?

A

Potent inhibitors of the CYP 450 enzymes

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12
Q

How do the Calcineurin Inhibitiors, Ciclosporin & Tacrolimus work?

A
  • Ciclosporin binds to Cylophillin protein
  • Tacrolimus binds to Tacrolimus-binding protein
  • The drug/ protein complexes bind Calcineurin, which signals activated T cells to begin IL-2 transcription.
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13
Q

What is Mycophenolate Mofetil for?

A
  • Mainly in transplantation

- Can be used as Induction & Maintenance therapy for Lupus and Vasculitis

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14
Q

What variation of Mycophenolate Mofetil can be given to those with GI issues?

A

Mycophenolic acid

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15
Q

How does Mycophenolate Mofetil work?

It is a prodrug

A
  • Impairs B and T cell proliferation

spares other rapidly dividing cells

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16
Q

List 5 ADRs of Mycophenolate Mofetil

A
  • Nausea
  • Vomiting
  • Diarrhoea
  • Mucositis
  • Myelosuppression
17
Q

How does Cyclophosphamide work?

A

Suppresses B & T cell activity

Very good at inducing remission

18
Q

Describe the pharmacodynamics of Cyclophosphamide

A
  • Is a prodrug

- Active metabolite is 4-HC (4-hydroxycyclophosphamide)

19
Q

Suggest a renal ADR of Cyclophosphamide

How is this prevented?

A

One of its active metabolites, Acrolein is toxic to bladder epithelia and can-> Haemorrhage Cystitis

Use of aggressive hydration + Mesna (‘mops up’ Acrolein)

20
Q

List 2 non renal ADRs of Cyclophosphamide

A
  • Increased risk of bladder cancer, Lymphoma, Leukaemia

- Infertility (Give a Gonatropin receptor antagonist to protect eggs)

21
Q

Compare Cyclophosphamide and Mycophenolate Mofetil with regards to safety and treating Lupus

A

MMF is safer and just as effective in treating Lupus

22
Q

Methotrexate is the gold standard treatment for RA and is most commonly used in rheumatology.

Suggest 3 other uses

A
  • Malignancy
  • Psoriasis
  • Crohn’s
23
Q

How does Methotrexate work?

A
  • Competitive inhibition of DHFR, Dihydrofolate Reductase (x1000 the affinity of Folate)
  • Thus, inhibits synthesis of DNA, RNA and proteins (greater toxic effect on cells that are dividing more quickly)
24
Q

Does Methotrexate act on Folate to combat non-malignant disease?

A

No, mechanism is unclear

25
Q

Is Methotrexate dosed daily or weekly?

How much is protein-bound?

A

Weekly (never daily)

50%

26
Q

List some ADRs of Methotrexate

A
  • Myelosuppression
  • Mucositis
  • Hepatitis/ cirrhosis
  • Pneumonitis (rare)
  • Risk of infection
  • HIGHLY TERATOGENIC (Abortifacient)
27
Q

Sulfasalazine is a conjugate of Salicylicate, that works in the gut (treating IBD)

How does it work?

A
  • Inhibits T cell proliferation and IL-2 production

- Reduced chemotaxis and degranulation of neutrophils

28
Q

List 5 ADRs of Sulfasalazine

A
  • Myelosuppression
  • Hepatitis
  • Rash
  • Nausea
  • Abdo pain
  • Vomiting
29
Q

List some positive features of Sulfasalazine

A
  • Monitoring can stop after 2 years/ long term use as ADRs are most likely to be in initial period
  • No carcinogenic potential
  • Safe in pregnancy
  • Very few DDIs (caution with PPIs)
30
Q

How do the ‘Biologicals’ work usually?

A

Block TNF-Alpha leading to;

  • Reduced inflammation
  • Reduced angiogenesis
  • Reduced joint destruction
31
Q

Suggest an ADR of the “Biologicals’

A
  • Risk of TB reactivation (screen for latent before treatment)