DMARDs (6.1)

Question 1

What is the first choice treatment for Rheumatoid Arthritis?

Answer 1

Methotrexate

Question 2

What is the mode of action of Methotrexate in non malignant disease?

Answer 2

Increase intracellular Adenosine causing a decrease in T cell proliferation
Inhibits T cell activation

Question 3

What is the mode of action of Methotrexate in treating malignant disease?

Answer 3

Folic acid antagonist so decreases purine synthesis preventing DNA synthesis

Question 4

What are some of the ADRs of Methotrexate?

Answer 4

Mucositis
Myelosuppression
Teratogenic
Abortifacient
Hepatitis
Cirrhosis

Question 5

What drugs interact with Methotrexate treatment?

Answer 5

NSAIDS cause displacement of Methotrexate from plasma proteins causing an increase in free drug and therefore more ADRs

Question 6

What group of patients need to monitored closely when taking Methotrexate?

Answer 6

Those with renal impairment as the drug is excreted renally - More likely to have ADRs

Question 7

How is Methotrexare administered?

Answer 7

Once a week Intra-Muscularly as the metabolites (Polyglutamates) have long half lives

Question 8

What is an alternative drug used for RA in pregnant women?

Answer 8

Sulfasalazine

Question 9

What is Sulfasalazine?

Answer 9

Combination of Salicylate (Anti inflammatory) and an antibiotic (Sulfapyridine)

Question 10

What is the mode of action of Sulfasalazine?

Answer 10

Decreases proliferation of T cells via apoptosis/Decreased IL-2 production
Reduces chemotaxis of neutrophils

Question 11

What are some ADRs of Sulfasalazine?

Answer 11

Diarrhoea (Due to the antibiotic)
Hepatitis
Rash
Myelosuppression

Question 12

Why is Sulfasalazine effective at treating Inflammatory bowel disease?

Answer 12

It is cleaved and sits in the large bowel

Question 13

What is the mode of action of Anti-TNF agents?

Answer 13

Act on VEGF and IL-8 to reduce inflammation and angiogenesis.

Question 14

What are some of the ADRs of Anti-TNF agents?

Answer 14

Increased risk of infections
Reactivation of latent TB
Expensive

Question 15

Why do patients need a TB screening before initiating Anti-TNF treatment?

Answer 15

TNF helps to enclose TB in granulomas making it latent. Anti-TNF agents cause reactivation of TB so all patients should be screened for TB before beginning treatment

Question 16

What is Rituximab?

Answer 16

A monoclonal antibody to CD20 which causes apoptosis of B cells Often used in combination with Methotrexate

Question 17

What is the mode of action of Prednisone?

Answer 17

Corticosteroid - lipophillic
Binds glucocorticoid receptor inside cell - complex goes to nucleus and alters transcription of pro-inflammatory proteases

Question 18

Name some of the ADRs of Prednisone?

Answer 18

Stimulates appetite
Aggressive mood changes
Long term high does can cause Cushing’s syndrome

Question 19

Why do patients need to be taken off Prednisone slowly?

Answer 19

It is a corticosteroid so takes over the role of the Adrenal cortex (Which becomes insufficient to meet the body’s demands)
If drug stopped suddenly then the Adrenal cortex cannot meet the needs of the body and an Addisonian crisis may occur = low BP causing low perfusion

Question 20

What is Mycophenolate Mefetil?

Answer 20

A prodrug that inhibits inosine monophosphate dehydrogenase which is needed for guanine synthesis. (Guanine is used in B&T cell proliferation)
Spares rapidly dividing cells as they have a guanine salvage pathway

Question 21

What are the ADRs of Mycophenolate Mefetil?

Answer 21

Myelosuppression
Increased risk of infection
Risk of birth defects and miscarriage
Increases blood cholesterol
Excreted renally so can become toxic in those with renal issues

Question 22

What are the most appropriate uses for Mycophenolate Mefetil?

Answer 22

Systemic lupus erythematosus
Vasculitis
Crohn’s disease
Transplants

Question 23

What is Cyclophosphamide?

Answer 23

An alykylating agent that cross links DNA so it cannot replicate
Suppresses B&T cell activity
Given as a prodrug

Question 24

What are the ADRs of Cyclophosphamide?

Answer 24

Targets rapidly dividing cells meaning there is a high risk of infertility
Haemorrhagic cystitis

Question 25

How can Cyclophosphamide increase the risk of Haemorrhagic cystitis?

Answer 25

A metabolite (Acrolin) is toxic to the epithelium of the bladder
The risk can be decreased by ensuring the patient is well hydrated

Question 26

What are the most appropriate uses for Cyclophosphamide?

Answer 26

Lymphoma
Leukaemia
Systemic lupus erythematosus
Vasculitis

Question 27

What is Azathioprine?

Answer 27

A drug that is cleaved to 6-mercaptophrine which is an antimetabolite that decreases DNA & RNA synthesis

Question 28

Why are some patients more at risk of developing myelosuppression when being treated with Azathioprine?

Answer 28

6-mercaptophrine is metabolised by Thiopurine methyltransferase which can vary between patients (low levels of the enzyme = higher risk of myelosuppression)

Question 29

What are the ADRs of Azathioprine?

Answer 29

Myelosuppression
Increased risk of malignancy
Increased risk of infection
Hepatitis

Question 30

What are the main uses of Azathoprine?

Answer 30

Inflammatory Bowel Disease

Atopic dermatitis

Question 31

What is Ciclosporin?

Answer 31

A Calcineurin inhibitor that binds to cyclophilin protein on T helper cells
Prevents IL-2 production

Question 32

What is Tacrolimus?

Answer 32

A Calcineurin inhibitor that binds to tacrolimus binding protein on T helper cells
Prevents IL-2 production

Question 33

What are the ADRs of Calcineurin inhibitors?

Answer 33

Nephrotoxic
Vomiting
Diarrhoea

Question 34

What group of patients are Calcineurin inhibitors particularly useful for?

Answer 34

Those with Rheumatoid arthritis and Cytopenias as it does not affect the bone marrow

Question 35

What are Calcineurin inhibitors mainly used for?

Answer 35

Transplants
Psoriasis
Atopic dermatitis
Patients with Rheumatoid arthritis and Cytopenias