2.3 Immunosuppressive medication Flashcards
What is the alkylating agent?
Cyclophosphamide
What are the antimetabolites?
azatthioprine
What are the calcineurin inhibitors?
Cyclosporin and tacrolius
What are the purine synthesis inhibitors?
Mycophenylate and Mofetil
When do you use immunosuppressive medication in rheumatology?
Second line therapy or when major organs are threatened
When is azathioprine used?
transplant rejection, autoimmune disease, RA, SLE, seronegative inflammatory arthritis and polymyositis
What is the mechanism of azathioprine
Interferes with intracellular purine synthesis in the S phase resulting in decreased numbers of circulating T and B lymphocytes, reduced immunoglobulin synthesis and reduced IL-2 secretion
How is azathioprine converted into the active drug?
the enzyme TPMT converts 6-mecaptopurine into the active methyl mercaptopurine (TMPT levels will be measured prior to azathioprine)
What do you need to measure before giving azathioprine?
TPMT
What drug does azathioprine interact with?
Allopurinol - This is a XO inhibitor so will slow teh elimination of 6 mecaptopurine so you will need to lower the dose
What are the adverse effects of azathioprine?
Anorexia, nausea, vomiting, LFT abnormalaties Leukopenia and thrombocytopenia Bacterial and viral infections Increased risk of skin cancer Infertility
What is the mechanism of cyclophosphamide
Causes cross-linking of macromolecules including RNA, DNA and protein. The DNA cross linking leads to impaired DNA replication causing cell death and altered cell function - works on all stages of the cell cycle
How is cyclophosphamide administered?
IV as monthly pulses or daily oral dose
How is cyclophosphamide converted into its active form?
Cytochrome p54 converts it in the liver
What are the toxic effects of cyclophosphamide?
WCC reduction 10-14 days after dose
Bladder toxicity (minimise by adequate hydration)
Increased risk of lymphoma, leukaemia and skin cancer
Teratogenic
Gonadal toxicity
What are the indications for cyclophosphamide use?
Renal involvement in SLE
Vasculitis - when major organs are threatened
Inflammatory autoimmune conditions that threaten major organs
What is the mechanism of the calcineurin inhibitors (cyclosporin and tacrolimus)
Selectively inhibit transcription of IL-2 and several other cytokines (mainly T lymphocytes)
Inhibit the enzyme calcineurin which prevents the translocation of nuclear factor of T cells (NFAT) preventing IL-2 production
What are the uses of cyclosporin?
RA Psoriasis and psoriatic arthritis Juvenile arthritis Polymyositis and dermatomyositis Transplants
What are eh uses of tacrolimus?
Organ transplant rescue therapy in patients with rejection despite cyclosporin use
Adult RA
systemic sclerosis
What are the toxicities of calcineurin inhibitors?
Renal dysfunction Hypertension Tremor Gum hyperplasia Hirstruism Diabetes mellitus
What is the mechanism of mycophenolate mofetil?
Prevents lymphocyte proliferation by affecting the purine synthesis of activated lymphocytes. - Inhibits the enzyme inosine monophosphate dehydrogenase
What are the adverse effects of mycophenylate mofetil?
Safer than cyclophosphaide nauesea, vomiting, abdominal cramping Cytopenia Infection Potentially teratogenic
