Treating Rheumatological Disorders Flashcards
What is rheumatoid arthritis?
An autoimmune multisystem disease which presents with morning stiffness, symmetrical arthritis and rheumatoid nodules.
What is the pathophysiology of rheumatoid arthritis?
There is an altered balance between pro and anti inflammatory signals. This causes inflammatory change and proliferation of synovium which leads to dissolution of cartilage and bone.
What is lupus?
What systems does it affect?
A multisystem disease affecting the nervous system (seizures, psychosis, headaches, low grade fever), heart and lungs (pericarditis, myocarditis, endocarditis, pleuritis), kidneys (oedema, hypertension, proteinuria), blood (anaemia, thrombocytopenia).
What are the major groups of rheumatological drugs?
Corticosteroids- best avoided in this case
Azothioprine
Mycophenolate mofetil
Calcineurin inhibitors
Disease Modifying Anti Rheumatic Drugs (DMARDs)
What is the mechanism of action of azothioprine?
It is cleaved to 6MP by TPMT. 6MP decreases DNA and RNA synthesis.
What is azothioprine used for?
SLE and vasculitis as a maintenance therapy
What enzyme is it important to check for before starting someone on azothioprine?
TPMT activity- low levels of TPMT risk myelosuppression on azothioprine.
What monitoring does azothioprine require ?
FBC- risk of myelosuppression
Infection markers- risk of infection
LFTs- risk of hepatitis.
What is the mechanism of action of mycophenolate mofetil?
Inhibits guanosine synthesis- impairs B and T cell proliferation. Spares other rapidly dividing cells as they have guanosine salvage pathways.
In what situations is mycophenolate mofetil used?
Used mainly in transplantation but also in induction and maintenance therapy for lupus.
What are the common side effects of mycophenolate mofetil?
Nausea
Vomiting
Diarrhoea
Myelosuppression.
What is the mechanism of action of calcineurin inhibitors?
Active against T helper cells. Prevents production of IL2 via calcineurin inhibition.
What are some examples of calciuneurin inhibitors?
Ciclosporin and tacrolimus.
What is the main use of calciuneurin inhibitors?
Mainly in transplantation, but also atopic dermatitis and psoriasis.
What are the major side effects of calciuneurin inhibitors?
Renal toxicity- not often used. GFR and BP are measured when it is being used.
What are the different types of DMARDs?
Sulphalazine
Cyclophosphamide
Methotrexate
Anti TNF agents
What is the mechanism of action of methotrexate in non malignant disease?
Inhibition of T cell activation,
Suppression of intercellular adhesion molecule expression.
In what situations is methotrexate indicated?
Crohns disease
RA
Malignancy
Psoriasis
What are the adverse effects of methotrexate?
Mucositis Marrow suppression Hepatitis, cirrhosis Pneumonitis Immunosuppression Teratogenic
What is the mechanism of action of cyclophosphamide?
A cytotoxic alkylating agent that cross links DNA so that it cannot replicate. So suppresses T cell and B cell activity.
What is cyclophosphamide indicated for?
Lymphoma, leukemia, solid cancers, lupus nephritis, wegeners granulomatosis (ANCA vasculitis),
lupus (mycophenolate mofetil is safe and as effective)
What are the side effects of cyclophosphamide?
It is excreted by the kidney. One of its metabolites- acrolein- is toxic to bladder epithelium so can lead to haemorrhagic cystitis. Can be prevented with aggressive hydration.
Can also cause increased risk of bladder cancer, lymphoma and leukemia.
What monitoring is required with cyclophosphamide?
FBC, adjustment of dose is required in renal impairment
What is the mechanism of action of sulphalazine?
Inhibits proliferation of T cells and may induce apoptosis. Inhibits IL2 production. Causes reduced neutrophil chemotaxis and reduced degranulation.
What are the side effects of sulphalazine?
Myelosuppression, hepatitis, rash.
Nausea, abdo pain, vomiting.
What is the benefit of using sulphalazine?
Very few drug interactions, safe in pregnancy, no long term monitoring needed.
What are the newer biologicals being introduced?
Monoclonal antibodies designed to block any given substance in body or to target any specific cell type. Eg rituximab.
What is the effect of anti TNF alpha drugs?
Decreased inflammation
Decreased angiogenesis
Decreased joint destruction
