2.3 Immunosuppressive medication Flashcards Preview

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Flashcards in 2.3 Immunosuppressive medication Deck (22)
1

What is the alkylating agent?

Cyclophosphamide

2

What are the antimetabolites?

azatthioprine

3

What are the calcineurin inhibitors?

Cyclosporin and tacrolius

4

What are the purine synthesis inhibitors?

Mycophenylate and Mofetil

5

When do you use immunosuppressive medication in rheumatology?

Second line therapy or when major organs are threatened

6

When is azathioprine used?

transplant rejection, autoimmune disease, RA, SLE, seronegative inflammatory arthritis and polymyositis

7

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

8

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)

9

What do you need to measure before giving azathioprine?

TPMT

10

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

11

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

12

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

13

How is cyclophosphamide administered?

IV as monthly pulses or daily oral dose

14

How is cyclophosphamide converted into its active form?

Cytochrome p54 converts it in the liver

15

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

16

What are the indications for cyclophosphamide use?

Renal involvement in SLE
Vasculitis - when major organs are threatened
Inflammatory autoimmune conditions that threaten major organs

17

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

18

What are the uses of cyclosporin?

RA
Psoriasis and psoriatic arthritis
Juvenile arthritis
Polymyositis and dermatomyositis
Transplants

19

What are eh uses of tacrolimus?

Organ transplant rescue therapy in patients with rejection despite cyclosporin use
Adult RA
systemic sclerosis

20

What are the toxicities of calcineurin inhibitors?

Renal dysfunction
Hypertension
Tremor
Gum hyperplasia
Hirstruism
Diabetes mellitus

21

What is the mechanism of mycophenolate mofetil?

Prevents lymphocyte proliferation by affecting the purine synthesis of activated lymphocytes. - Inhibits the enzyme inosine monophosphate dehydrogenase

22

What are the adverse effects of mycophenylate mofetil?

Safer than cyclophosphaide
nauesea, vomiting, abdominal cramping
Cytopenia
Infection
Potentially teratogenic