Immunosuppressants Flashcards
What are 2 treatment goals of Rheumatoid Arthritis?
- Symptom relief
- Prevent joint destruction (Erosion can’t be reversed)
Describe the overall treatment strategy for RA
- Early use of disease-modifying drugs
- Use of adequate doses & combinations of drugs
- Avoid long term corticosteroid use
Lupus is photosensitive. What organs can it affect?
All of them
How do Corticosteroids work as Immunosuppressants?
- Prevent IL-1 and IL-6 production by macrophages
- Inhibit all stages of T cell activation
Name one of the ‘biological’ disease modifying anti-rheumatic drugs (DMARDs) that is used to treat RA, Lupus and Vasculitis
Rituximab (Causes B cell apoptosis)
Describe the use of Azathioprine in treating;
- Lupus & Vasculitis
- RA
- IBD
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
Describe the pharmacodynamics of Azathioprine and its clinical significance
- 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)
List 5 ADRs of Azathioprine
ALL Immunosuppressants have these ADRs
- Bone marrow/ Myelosuppression (monitor FBC)
- Increased risk of malignancy (especially transplant patients)
- Mucositis
- Increased risk of infection
- Hepatitis (monitor LFT)
Ciclosporin and Tacrolimus are members of what drug class?
What are they used for?
Calcineurin inhibitors
- Transplantation
- Atopic dermatitis
- Psoriasis
Why should BP and GFR be checked regularly in patients who are using Calcineurin Inhibitiors?
Can cause renal toxicity
How do Calcineurin Inhibitiors interact with CYP 450 enzymes?
Potent inhibitors of the CYP 450 enzymes
How do the Calcineurin Inhibitiors, Ciclosporin & Tacrolimus work?
- 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.
What is Mycophenolate Mofetil for?
- Mainly in transplantation
- Can be used as Induction & Maintenance therapy for Lupus and Vasculitis
What variation of Mycophenolate Mofetil can be given to those with GI issues?
Mycophenolic acid
How does Mycophenolate Mofetil work?
It is a prodrug
- Impairs B and T cell proliferation
spares other rapidly dividing cells
List 5 ADRs of Mycophenolate Mofetil
- Nausea
- Vomiting
- Diarrhoea
- Mucositis
- Myelosuppression
How does Cyclophosphamide work?
Suppresses B & T cell activity
Very good at inducing remission
Describe the pharmacodynamics of Cyclophosphamide
- Is a prodrug
- Active metabolite is 4-HC (4-hydroxycyclophosphamide)
Suggest a renal ADR of Cyclophosphamide
How is this prevented?
One of its active metabolites, Acrolein is toxic to bladder epithelia and can-> Haemorrhage Cystitis
Use of aggressive hydration + Mesna (‘mops up’ Acrolein)
List 2 non renal ADRs of Cyclophosphamide
- Increased risk of bladder cancer, Lymphoma, Leukaemia
- Infertility (Give a Gonatropin receptor antagonist to protect eggs)
Compare Cyclophosphamide and Mycophenolate Mofetil with regards to safety and treating Lupus
MMF is safer and just as effective in treating Lupus
Methotrexate is the gold standard treatment for RA and is most commonly used in rheumatology.
Suggest 3 other uses
- Malignancy
- Psoriasis
- Crohn’s
How does Methotrexate work?
- 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)
Does Methotrexate act on Folate to combat non-malignant disease?
No, mechanism is unclear
Is Methotrexate dosed daily or weekly?
How much is protein-bound?
Weekly (never daily)
50%
List some ADRs of Methotrexate
- Myelosuppression
- Mucositis
- Hepatitis/ cirrhosis
- Pneumonitis (rare)
- Risk of infection
- HIGHLY TERATOGENIC (Abortifacient)
Sulfasalazine is a conjugate of Salicylicate, that works in the gut (treating IBD)
How does it work?
- Inhibits T cell proliferation and IL-2 production
- Reduced chemotaxis and degranulation of neutrophils
List 5 ADRs of Sulfasalazine
- Myelosuppression
- Hepatitis
- Rash
- Nausea
- Abdo pain
- Vomiting
List some positive features of Sulfasalazine
- 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)
How do the ‘Biologicals’ work usually?
Block TNF-Alpha leading to;
- Reduced inflammation
- Reduced angiogenesis
- Reduced joint destruction
Suggest an ADR of the “Biologicals’
- Risk of TB reactivation (screen for latent before treatment)
