Immunosupressants Flashcards
Rheumatoid arthritis.
Give four deformities that can arise in RA.
What cells become activated in RA?
Give three main cytokines released by macrophages that lead to activation of fibroblast like synoviocytes.
What are two ABs that can be looked for in serology? Which one is more specific?
Give four non-MSK manifestations of RA.
Give two anti-inflammatory markers?
Ulnar deviation of wrist
Z-deformity of thumb (MCPJ HE, IPJ F)
Swan neck
Boutineirre
Fibroblast-like-synoviocytes.
IL-1, IL-6 and TNFa
Rheumatoid factor (IgM) Anti-citrullinated protein antibody (more specific)
Rheumatoid nodules
Anaemia of chronic disease
Thrombocytosis
Pleural effusion
IL-4
TGF-Beta
Give some ways in which glucocorticoids are anti-inflammatory.
Inhibition of NFkB
Production of lipocortin - inhibit PLA2
Decrease IL-1 and IL-6
Inhibit T cell activation
Azathiprine.
Uses?
Why should TPMT be tested for before prescribing?
What is its MOA?
Why should it be given with care in transplant patients?
Give 3 other side effects of immunosuppressants in general.
Why monitor FBC?
SLE and Vasculitis (maintenance)
IBD
Atopic dermatitis
Bullous skin disease
TPMT (thiopurine methyltransferase) - highly polymorphic - low/absent levels - myelosupression risk.
Inhibition of DNA and RNA synthesis due to it being an antimetabolite
Increased risk of malignancy
Bone marrow supression
Increased risk of infection
Hepatitis
Because risk of myelosupression
Calcinuerin inhibitors.
Name two. Distinguish between MOA.
Where are they widely used and give two other uses?
Tacrolimus and ciclosporin
Tacrlimus - binds tacrolimus binding protein
Cyclosporin binds - cyclophylin
Binding of these cause inhibition of calcineurin which usually phosphatases NFAT and NFAT will go an cause IL2 production and subsequently clonal expansion of T cells.
Transplantation
Atopic dermatitis
Psoriasis
Inducers and inhibitors.
PCARBS - inducers
ODEVICES - inhibitors
Phenytoin Carbamezepine Alcohol Rifampicin Barbituates Sulfonylureas St Johns wort
ODEVICES
Omeprazole (both) Disulfiram Erythromycin Valproate Isoniazid Cimetidine/ Ciprofloxacin Ethanol Sulfonamide
Mycophenolate mofetil.
Derived from?
MOA?
Why are other cells not affected by this?
Common side effects?
Serious?
Mainly used with and what for?
Penicillium stoloniferum
Inhibits inosine monophosphate dehydrogenase which is required from guanosine synthesis in B and T cells.
T and B cells use almost purely denovo purine synthesis because of guanosine salvage pathways
Nausea, vomiting and diarrhoea
Myelosupression
With a calcineurin inhibitor and steroid for prevention of transplant rejection.
Cyclophosphamide mechanism of action cancer and immunomodualtory.
What are they two main active metabolites of cyclophosphamide?
2 things that can reduce chances of haemorrhagic cystitis?
Why does it not pose the typical chemotherapy agent side effects?
Three cancers it increases the risk of?
True or false mycophenolate mofetil is safer and more effective in lupus nephritis.
Give some indications.
Alkylating agent - cross links DNA - prevents it from replicating.
Supression of B and T cell activity
4-hydroxycyclophosphamide
phosphoramide mustard
Mesna
Adequate hydration
High levels of ALDH in bone marrow, liver and intestinal epithelium converts 4-hydroxycyclophosphamide to carboxycyclophosphamide.
Bladder, lymphoma and leukaemia
Infertility
True
Lymphoma, leukaemia, GVHD, Wegener’s granulomatosis (ANCA vasculitis)
Lupus nephritis
Methotrexate.
Other than RA indications?
Possible non-malignant MOA.
Why may it better to be given IM?
Why weekly dosing?
Why may concurrent NSAID prescription be bad?
Give adverse effects that can be decreased by folic acid supplementation.
Give 4 others.
Psoriasis
Crohn’s disease
Cancers
AICAR transformylase inhibition - inhibition of accumulation of intracellular adenosine
Inhibition of T cell activation
Supression of intercellular adhesion molecule expression by T cells.
Because IM bioavailability is higher vs PO
(76% vs 33%)
Converted to polyglutamates with long half lives
50% protein binding therefore can displace.
Mucositis
Marrow supression
Pneumonitis
Infection
Hepatitis (cirrhosis)
HIGHLY TERATOGENIC and ABORTIFACIENT
Sulfasalazine.
Made of which two drugs?
Why highly effective in IBD?
MOA?
Give 3 side effects.
Pregnancy?
Sulfapyradine and 5-aminosalicylicacid
T cells and neutrophil effects.
Inhibition of proliferation, T-cell apoptosis and inhibition of IL-2 production
Neutrophil reduced chemotaxid and degranulation.
Because 5-ASA once cleaved by gut bacteria is largely unabsorbed.
Myelosupression
Hepatitis
Rash
Nause/ N/V
Safe in pregnancy.
Anti-TNFa.
ADAL GOt CERTified for INFLIcting pain on TNFa.
Which one is herceptin?
What should you screen for before anti-TNFa therapy?
Rituximab MOA? Used?
Adalimumab
Golimumab
Certolizumab
Infliximab
Trastuzumab
TNFa needed for maintaining granulomas therefore screening for latent TB needed
CD20 targeted
RA
