Immunosuppression Flashcards
Name the 3 anti-TNF drugs used in RA?
Infliximab
Adalimumab
Etanercept
What are the main side effects of anti-TNF drugs
- name 4
- infection risk: Hazard ratio = 1.2 - 1.5 for serious infection
- susceptibility to intracellular pathogens
- reactivation of latent TB - reactivation of HepB
(TNFaplha suppresses HBV replication)
- monitor serology 3 monthly and consider anti-viral prophylaxis - Risk of cancer is controversial - possible increase risk of lymphomas, although there is a baseline increased risk with RA alone
- consider using rituximab instead of TNF-inhibitors if Hx of malignancy - May worsen CHF - avoid
rare: exacerbation of previous quiescent MS, optic neuritis, ILD
How does Rituximab work?
anti CD20 (B cells)
What conditions is Rituximab used for?
Lymphoma (R in R-CHOP)
- CD20 positive B cell non-Hodgkins lymphoma
- CD20 positive diffuse large B cell
CLL
RA
Granulomatosis with polyangiitis (Wegener’s) and Microscopic Polyangitis
What are the important side effects of Rituximab?
- Increased risk of all infections
- PML
- consider if new or worsening neurology
- withheld Rituximab and test for JC viral DNA - Infusion reactions
- predmedicate and slow infusion - Hep B reactivation
- screen with HBsAg and HBcAB prior to starting
How does Methotrexate work?
dihydrofolate reductase antagonist
competitively inhibits dihydrofolate reductase preventing the conversion of folic acid to tetrahydrofolate.
The impairs the synthesis of thymidylic acid and purines, inhibiting DNA synthesis and cell production
Methotrexate acts specifically on the S-phase of the cell cycle.
Tissues with a high cellular proliferation rate such as neoplastic tissue, bone marrow, epithelial cells or foetal cells seem to be the most susceptible.
What are the side effects of Methotrexate?
Hepatotoxicity* - diagnosed with liver biopsy - discourage ETOH use Nausea* Interstitial pneumonitis, fibrosis Myelosuppression Oral ulcers Hair loss
- combine with low dose folic acid to reduce GI SEs and hepatotoxicity
How do you reverse Methotrexate toxicity?
Toxicity - myelosuppression and GI toxicity
Treatment: folinic acid
Can methotrexate be used in pregnancy?
no - category D
also not safe in breast feeding
women of child-bearing age should be on reliable contraception for 3 months after stopping MTX
What are some important drug interactions with Methotrexate?
Avoid co-administration with trimethoprim, co-trimoxazole and probenecid (folate depleting)
What tests should be performed before initiating MTX?
Liver functions
Renal function (primarily really excreted therefore must reduce dose)
FBC
CXR
monitor bloods every 1-3 months
How does Leflunomide work?
Inhibits dihydro-orotate dehydrogenase (key enzyme in de novo pyrimidine synthesis)
Pyrimidines required for T-cell proliferation and activation
What are the side effects of Leflunomide?
Similar SE profile to MTX
Diarrhoea
Peripheral neuropathy
ILD
How do you manage Leflunomide toxicity?
Cholestyramine washout
Leflunomide has extensive entzroheptic recirculation
- must be done prior to conceiving or urgently if woman becomes unexpectedly pregnant on Leflunomide
Why would you chose to use Sulphasalazine in RA?
When MTX is not tolerated, ongoing ETOH consumption
