Immunosuppresson - Rheumatology Flashcards
What is rheumatoid arthritis?
An autoimmune multi-system disease
Family common: UK prevalence of 1%
Initially localised to synovium
Inflammatory change and proliferation of synovial (pannus) and leading to dissolution of cartilage and bone
Describe the pathogenesis of RA
Immune system becomes hyperactive.
The over expression of metalloproteinases leads to inflammation of the joints and thickening of the joint capsule.
How do we diagnose RA??
Clinical criteria: Morning stiffness >1hour Arthritis of >3 joints Arthritis of hand joins Symmetrical arthritis Rheumatoid nodules
Non clinical:
Serum rheumatoid factor / Anti-CCP antibodies
X-Ray changes
What are the goals of RA treatment?
Symptom relief
Prevention of joint destruction
Describe the treatment strategy of RA
Early use of disease-modifying drugs Aim to achieve good disease control Use of adequate dosages Use of combinations of drugs Avoidance of long-term corticosteroids
What is SLE?
It is an autoimmune disease in which the immune system attaches many different systems of the body.
Called lupus as the lupus rash looks like you have been bitten by a wolf.
Symptoms vary between people and may be mild to severe.Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face
What is vasculitis?
Vasculitis is a group of disorders that destroy blood vessels by inflammation.[2] Both arteries and veins are affected.
L - leukocytic infultrates
F - fibrosis
T - thrombosis
What are the treatment goals in SLE and vasculitis?
Symptomatic relief
Reduction in mortality
Prevention of organ damage
Reduction in long term morbidity caused by disease and by drugs.
Give examples of some Immunosuppressants
Corticosteroids Methotrexate Azathioprine Cyclosporin Tacrolimus Mycophenolate mofetil Leflunomide Cyclophosphamide
How do corticosteroids work?
Prevent IL-1 and IL-6 production by macrophages.
Inhibits all stages of T cell activation.
What are the side effects fo steroids?
Osteoporosis Buffalo hump Heart attack High cholesterol Cararacrs Trunk obesity Diabetes Glaucoma
What are examples of some other DMARDs?
Non biologics:
Sulphasalazine
Hydroxychloriquinine
Biologics:
Anti-TNF
Rituximab
IL-6 inhibitors, JAK inhibitors
What is Azathioprine used for?
SLE and vasculitis as maintenance therapy
RA - very weak evidence
IBD
Dermatitis - Bullous skin disease
Many other uses as a ‘steroid sparing’ drug
Describe the pharmacodynamics of azathioprine
Either Azathioprine or 6-MP as 6-MP is metabolised by TPMP
6-MP better tolerated if vomiting - but, used more by GI
Need to check TPMT levels as it is highly polymorphic so a low /absent TPMT results in a risk of myelosupression.
Describe the MOA of azathioprine
Azathioprine is a prodrug.
At first it is slowly and almost completely converted to 6-mercaptopurine (6-MP) by reductive cleavage of the thioether (–S–).
6-MP is metabolized analogously to natural purines, giving thioguanosine triphosphate (TGTP) and thio-deoxyguanosine triphosphate (TdGTP) via thioinosine monophosphate (TIMP) and several further intermediates.
On a second path, the sulfur atom of 6-MP and TIMP is methylated. The end products of azathioprine metabolism are thiouric acid (38%) and various methylated and hydroxylated purines, which are excreted via the urine
What are the ADRs of Azathioprine?
Bone marrow suppression — monitor FBC
Increased risk of malignancy
Increase risk of infection
Hepatitis - monitor LFT
What are cacineurin inhibitors side for?
Cyclosporine and tacrolimus widely used in transplantation.
Also for topic dermatitis and psoriasis
Not often used in rheumatology because of renal toxicity (need to check BP and eGFR regularly)
