Immunosuppression Flashcards
What is the Pathogenesis of Rheumatoid Arthritis?
Pro inflammatory chemicals like T cells, IL-1 and IL-6
Outweigh
Anti-Inflammatory chemicals like IL-4 and B cells
This causes inflammation
How do you diagnose Rheumatoid?
Morning stiffness for over an hour
Arthritis of 3 or more joints
Arthritis of hand joints
Nodules (advanced, shouldn’t get to this)
What do Corticosteroids do?
Prevent IL-1 and 6 production by macrophages
Inhibit all stages of T cell activation
What are ADRs of Corticosteroids?
Weight gain
Striae
Glucose intolerance
Osteoporosis
What is Rheumatoid Arthritis?
Auto immune multi system disease
Inflammation in the joints
Which conditions is Azathioprine used for?
SLE
Vasculitis
Inflammatory bowel disease
Bullous skin disease
What is the mechanism of Azathioprine?
Cleaved to 6-MP
Works as an anti-metabolite to decrease DNA and RNA synthesis
What should you be careful of with Azathioprine?
Those with low or absent TPMT gene levels are likely to develop myelosuppression
Myelosuppression is a decrease in leucocytes, erythrocytes and thrombocytes
What are the ADRs of Azathioprine?
Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
What do Ciclosporins and Tacrolimus do?
Work against T helper cells
Prevent IL-2 production using calceurin inhibition
What conditions are Calcineurin inhibitors used in?
Atopic dermatitis
Psoriasis
What are the ADRs of Calcineurin inhibitors?
Nephrotoxicity
Hypertension
Hyperlipidaemia
How does Mycophenolate Mofetil work?
Inhibit enzyme that is required for guanosine synthesis
Impairs B and T cell proliferation
What are the ADRs of Mycophenolate Mofetil?
Nausea and vomiting
Myelosuppression
What is Methotrexate the gold standard for?
Rheumatoid Arthritis
What is the mechanism of action of methotrexate?
Inhibits enzymes involved in purine production
Accumulation of adenosine
Interacts with GPCRs on inflammatory cells to regulate their function
Also inhibits T cell activation
What is important about dosing of Methotrexate?
Must be given weekly (NOT DAILY)
What are ADRs of Methotrexate?
Mucositis
Marrow Suppression
Very teratogenic
What do you need to make sure you do with patients who take Methotrexate?
Toxicity monitoring
Chest X rays
FBC, LFT, U&E, creatinine
What are the effects of Sulfasalazine?
Inhibition of T cell proliferation by:
- Inhibition of IL-2 production
- T cell apoptosis
- inhibition of proliferation
Decreases chemotaxis and degranulation of neutrophils
What are the ADRs of Sulfasalazine?
Myelosuppression
Hepatitis
Rash
What are the actions of Rituximab?
Binds specifically to surface marker CD20
Deplete B cells
What are inducers of Cytochrome CYP450?
Rifampicin
Carbamezepine
Phenytoin
Omeprazole
What are some inhibitors of Cytochrome CYP450?
Ciprofloxacin
Antifungals
Paroxetine
Fluoxetine
