Immunosuppressants

Question 1

What are 2 treatment goals of Rheumatoid Arthritis?

Answer 1

• Symptom relief

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

Question 2

Describe the overall treatment strategy for RA

Answer 2

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

Question 3

Lupus is photosensitive. What organs can it affect?

Answer 3

All of them

Question 4

How do Corticosteroids work as Immunosuppressants?

Answer 4

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

- Inhibit all stages of T cell activation

Question 5

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

Answer 5

Rituximab (Causes B cell apoptosis)

Question 6

Describe the use of Azathioprine in treating;

• Lupus & Vasculitis
• RA
• IBD

Answer 6

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

Question 7

Describe the pharmacodynamics of Azathioprine and its clinical significance

Answer 7

• 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)

Question 8

List 5 ADRs of Azathioprine

ALL Immunosuppressants have these ADRs

Answer 8

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

Question 9

Ciclosporin and Tacrolimus are members of what drug class?

What are they used for?

Answer 9

Calcineurin inhibitors

• Transplantation
• Atopic dermatitis
• Psoriasis

Question 10

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

Answer 10

Can cause renal toxicity

Question 11

How do Calcineurin Inhibitiors interact with CYP 450 enzymes?

Answer 11

Potent inhibitors of the CYP 450 enzymes

Question 12

How do the Calcineurin Inhibitiors, Ciclosporin & Tacrolimus work?

Answer 12

• 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.

Question 13

What is Mycophenolate Mofetil for?

Answer 13

• Mainly in transplantation

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

Question 14

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

Answer 14

Mycophenolic acid

Question 15

How does Mycophenolate Mofetil work?

It is a prodrug

Answer 15

• Impairs B and T cell proliferation

spares other rapidly dividing cells

Question 16

List 5 ADRs of Mycophenolate Mofetil

Answer 16

• Nausea
• Vomiting
• Diarrhoea
• Mucositis
• Myelosuppression

Question 17

How does Cyclophosphamide work?

Answer 17

Suppresses B & T cell activity

Very good at inducing remission

Question 18

Describe the pharmacodynamics of Cyclophosphamide

Answer 18

• Is a prodrug

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

Question 19

Suggest a renal ADR of Cyclophosphamide

How is this prevented?

Answer 19

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

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

Question 20

List 2 non renal ADRs of Cyclophosphamide

Answer 20

• Increased risk of bladder cancer, Lymphoma, Leukaemia

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

Question 21

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

Answer 21

MMF is safer and just as effective in treating Lupus

Question 22

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

Suggest 3 other uses

Answer 22

• Malignancy
• Psoriasis
• Crohn’s

Question 23

How does Methotrexate work?

Answer 23

• 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)

Question 24

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

Answer 24

No, mechanism is unclear

Question 25

Is Methotrexate dosed daily or weekly?

How much is protein-bound?

Answer 25

Weekly (never daily)

50%

Question 26

List some ADRs of Methotrexate

Answer 26

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

Question 27

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

How does it work?

Answer 27

• Inhibits T cell proliferation and IL-2 production

- Reduced chemotaxis and degranulation of neutrophils

Question 28

List 5 ADRs of Sulfasalazine

Answer 28

• Myelosuppression
• Hepatitis
• Rash
• Nausea
• Abdo pain
• Vomiting

Question 29

List some positive features of Sulfasalazine

Answer 29

• 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)

Question 30

How do the ‘Biologicals’ work usually?

Answer 30

Block TNF-Alpha leading to;

• Reduced inflammation
• Reduced angiogenesis
• Reduced joint destruction

Question 31

Suggest an ADR of the “Biologicals’

Answer 31

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