(6.1) Immunosupressants and Arthritis Flashcards
Briefly describe the pathology of Arthritis.
1) T cell activation
2a) Produce Fibroblasts & Osteoclasts
3a) Produce collengenases
2b) Produce Rheumatoid factors -> activate IgG -> activates Macrophages
3b) Produce IL1, IL6, TNF Alpha -> Inflammatory cell influx
4) Pannus formation = effused joint, thickened synovium
5) Cartilage & bone erosion
What is the gold standard treatment of Rheumatoid Arthritis? What is its mechanism of action?
Methotrexate
= Folic acid antagonist -> -DNA & RNA synthesis
Suggest 2 indications of Sulfasazaline.
- Inflammatory bowel disease
- Rheumatoid arthritis
Before prescribing Sulfasazaline, what allergies do you need to check?
Sulfasazaline is a combination of two drugs, hence check allergies to:
- Aspirin-like
- Sulpha group
Why is Sulfasazaline good in treating Inflammatory bowel disease?
Poor GI breakdown, need bacterial enzymes in lower GI
What common ADRs do all immunosupressants have? How do you monitor the patients?
- Risk of malignancy
- Risk of infection
- Hepatitis
- FBC (check myelosupression)
- LFT (hepatic function)
- Creatinine and U&E (renal function)
Briefly describe the mechanism of action of Methotrexate. Suggest 4 indications.
- Folic acid antagoinist -> -DNA&RNA synthesis
- RA (gold standard)
- Psoriasis
- Malignancy
- Crohn’s disease
What is special about prescribing Methotrexate?
Weekly prescription, orally, IM, S/C
Suggest 4 ADRs (not the typical immunosupressant ones) of Metotrexate.
- Tetratogenic, Abortifacient
- Pneumonitis
- Mucotitis (responsive to folate supplements)
- Cirhosis
Which drug should be avoided when treating RA?
Methotrexate, tetratogenic & abortifacient
Briefly describe the mechanism of action of Corticosteroid. In the case of RA, what particular targets does it have?
- Lipid soluble -> enters cells -> nucleus
- Transactivation = -gene transcription
- Transrepression = -inflammatory response
- IL1 & IL6 produced by macrophages
Suggest some complications of long term Corticosteroids use.
Cushing’s Syndrome
A) Easy infection
B) Oppose insulin effects
- Hyperglycaemia -> Cataract & Glaucoma
- Hyperglycaemia -> avascular necrosis -> ulcers
- Lipogenesis -> moon shaped face & weight gain
- Proteolysis -> purple striae & bruising & muscle wasting & hair thinning
C) -Ca absorption -> Osteoporosis
D) CNS effects
E) Cross activity with Minerolocorticoid
- Hypertension
- Hypernaetramia & Hypokalaemia
What is special about prescribing Methotrexate?
Weekly prescription, orally, IM, S/C
Briefly describe the mechanism of action of Azathioprine. Suggest 4 indications.
- An antimetabolite of Purine-> -DNA&RNA synthesis
- Inflammatory bowel disease
- Atopic dermatitis
- RA
- SLE & Vasculitis (as maintenance)
Which drug should be avoided when treating RA?
Methotrexate, tetratogenic & abortifacient
Briefly describe the mechanism of action of Cyclophosphamide. Suggest 2 indications.
- Form crosslink with DNA -> -synthesis
- ANCA vasculitis
- Lupus nephritis (Mycophenolate Mofetil preferred)
Suggest 2 ADRs (not the typical immunosupressant ones) of Cyclophosphamide.
- Bladder cancer
- Infertility
Suggest 3 steroid sparing drugs.
- Methotrexate
- Azathioprine
- Cyclophosphamide
Briefly describe the mechanism of action of Azathioprine. Suggest 4 indications.
- An antimetabolite of Purine-> -DNA&RNA synthesis
- Inflammatory bowel disease
- Atopic dermatitis
- RA
- SLE & Vasculitis (as maintenance)
Why is the appropriate dosage of Azathioprine complex to determine?
wide genetic polymorphism of the enzymes needed to metabolise it
Briefly describe the mechanism of action of Cyclophosphamide. Suggest 2 indications.
- Form crosslink with DNA -> -synthesis
- ANCA vasculitis
- Lupus nephritis (Mycophenolate Mofetil preferred)
Suggest some ADRs (not the typical immunosupressant ones) of Cyclophosphamide.
- Bladder cancer
- Infertility
Briefly describe the mechanism of action of of Mycophenolate Mofetil. Suggest 2 indications.
- Impairs B & C cells proliferation
- Lupus nephritis
- Transplantation immunosupression
Suggest 1 ADRs (not the typical immunosupressant ones) of Mycophenolate Mofetil.
- Neutropenia
Briefly describe the mechanism of action of Calcineurin inhibitors. Name 2 drugs of its group. Suggest 2 indications.
- Binds to Calcineurin receptor on T lymphocytes -> -IL2 production -> - T cell activity
- Ciclosporin & Tacrolimus
- Eczema
- Transplantation suppression
Why did Calcineurin fall out of favour?
- Nephrotoxicity
- Hypertension
- Hyperuricaemia
- Hyperlipidaemia
- Nausea
- Diarrhoea
