Chapter 10 - DMARDs

Question 1

What is the MOA of methotrexate?

Answer 1

folic acid antagonist and its major site of action is the enzyme dihydrofolate reductase. Its main effect is inhibition of DNA synthesis but it also acts directly both on RNA and protein synthesis.

[dihydrofolate –> tetrahydrofolate –> purine synthesis –> DNA]

Dihydrofolate (dihydrofolate reductase) –> tetrahydrofolate

Question 2

What strength of methotrexate tablets are licensed for RA?

Answer 2

2.5mg tablets

Question 3

For someone who will be starting methotrexate, what monitoring requirements are needed?

Answer 3

Full blood count

Liver function tests

Question 4

How often should someone be monitored whilst taking methotrexate?

Answer 4

FBC + LFTs 1 before starting
Bloods every 1-2weeks initially until therapy stabilised
Then bloods every 2-3months thereafter for the duration of therapy

Question 5

What side effects should we counsel or look out for in patients taking methotrexate?

Answer 5

Bone marrow suppression/ blood dyscrasias - signs and symptoms suggestive of infection pay particular attention to in a methotrexate patient

Hepatotoxicity - liver cirrhosis reported with long term use of methotrexate

Pulmonary toxicity - seek medical attention if pt has new onset dyspnoea, cough or fever

Question 6

How is methotrexate excreted?

Answer 6

Mostly excreted via kidneys

Question 7

Can methotrexate be given to those with renal impairment?

Answer 7

Dependent on severity.

Dose reduction is required in renal impairment.

Avoid in severe renal impairment

Question 8

What advice would you give to men or women of child bearing potential regarding methotrexate?

Answer 8

Methotrexate is teratogenic. Effective contraception is required for both men and women during and for at least 3months after withdrawal of methotrexate treatment.

Fertility may be reduced during treatment (may be reversible on withdrawal)