2.3 Immunosuppressive medication

Question 1

What is the alkylating agent?

Answer 1

Cyclophosphamide

Question 2

What are the antimetabolites?

Answer 2

azatthioprine

Question 3

What are the calcineurin inhibitors?

Answer 3

Cyclosporin and tacrolius

Question 4

What are the purine synthesis inhibitors?

Answer 4

Mycophenylate and Mofetil

Question 5

When do you use immunosuppressive medication in rheumatology?

Answer 5

Second line therapy or when major organs are threatened

Question 6

When is azathioprine used?

Answer 6

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

Question 7

What is the mechanism of azathioprine

Answer 7

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

Question 8

How is azathioprine converted into the active drug?

Answer 8

the enzyme TPMT converts 6-mecaptopurine into the active methyl mercaptopurine (TMPT levels will be measured prior to azathioprine)

Question 9

What do you need to measure before giving azathioprine?

Answer 9

TPMT

Question 10

What drug does azathioprine interact with?

Answer 10

Allopurinol - This is a XO inhibitor so will slow teh elimination of 6 mecaptopurine so you will need to lower the dose

Question 11

What are the adverse effects of azathioprine?

Answer 11

Anorexia, nausea, vomiting, LFT abnormalaties 
Leukopenia and thrombocytopenia 
Bacterial and viral infections 
Increased risk of skin cancer 
Infertility

Question 12

What is the mechanism of cyclophosphamide

Answer 12

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

Question 13

How is cyclophosphamide administered?

Answer 13

IV as monthly pulses or daily oral dose

Question 14

How is cyclophosphamide converted into its active form?

Answer 14

Cytochrome p54 converts it in the liver

Question 15

What are the toxic effects of cyclophosphamide?

Answer 15

WCC reduction 10-14 days after dose
Bladder toxicity (minimise by adequate hydration)
Increased risk of lymphoma, leukaemia and skin cancer
Teratogenic
Gonadal toxicity

Question 16

What are the indications for cyclophosphamide use?

Answer 16

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

Question 17

What is the mechanism of the calcineurin inhibitors (cyclosporin and tacrolimus)

Answer 17

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

Question 18

What are the uses of cyclosporin?

Answer 18

RA 
Psoriasis and psoriatic arthritis 
Juvenile arthritis 
Polymyositis and dermatomyositis 
Transplants

Question 19

What are eh uses of tacrolimus?

Answer 19

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

Question 20

What are the toxicities of calcineurin inhibitors?

Answer 20

Renal dysfunction 
Hypertension 
Tremor 
Gum hyperplasia 
Hirstruism 
Diabetes mellitus

Question 21

What is the mechanism of mycophenolate mofetil?

Answer 21

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

Question 22

What are the adverse effects of mycophenylate mofetil?

Answer 22

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