DMARD'S

Question 1

What are an example of DMARDS?

Answer 1

Methotrexate, Leflunomide, Ciclosporin

Question 2

What is the aim of a DMARD?

Answer 2

to halt or reverse the underlying disease itself

Question 3

MOA methotrexate

Answer 3

Folic acid antagonist with cytotoxic and immunosuppressant activity.
-Can block adenosine uptake

Question 4

Does methotrexate cross the blood brain barrier?

Answer 4

No, it has low lipid solubility

Question 5

How is methotrexate taken into cells?

Answer 5

Through the folate transport system and is metabolised to polyglutamate derivatives, which are retained in the cell for weeks/months even in the absence of extracellular drug
Basically - stays in the body for a long time.

Question 6

What is Ciclosporin?

Answer 6

Fungal metabolite
-Crosses the gut wall
-Main metabolism Cyp450 = drug interactions

Question 7

Why is active infection a caution/contraindication to MTX?

Answer 7

Because it is an immunosuppressive drug, can therefore reduce the efficacy of the immune system to fight infection.

Question 8

Why is Ascities / pleural effusion a caution/contraindication to MTX?

Answer 8

MTX distributed into fluid, accumulates and can be re-excreted to prolong serum half-life increasing the risk o toxicity.

Question 9

Why significant hepatic impairment / liver disease a caution / contraindication to MTX?

Answer 9

Increased with concomitant hepatotoxic drugs

Question 10

Why is severe renal impairment a caution / contraindication with MTX?

Answer 10

MTX is renally cleared therefore impairment would lead to accumulation and increased risk of side effects. - Need to stay hydrated.

Question 11

If someone has renal impairment what should they do with the dose of MTX?

Answer 11

Reduce it.

Question 12

Is MTX safe in pregnancy?

Answer 12

It is teratogenic!

Question 13

How long is contraception required in males and female when using MTX?

Answer 13

3-6 months after treatment

Question 14

Why are the elderly cautioned / contraindicated in MTX?

Answer 14

Reduced folate reserves and reduced renal and hepatic function.

Question 15

What increases MTX toxicity?

Answer 15

Folate deficiency increases MTX toxicity.

Question 16

What deficiency can increase the risk of haemolytic anaemia when taking sulfasalazine?

Answer 16

Glucose-6-phosphate dehydrogenase deficiency

Question 17

Why is having liver impairment a contraindication / caution with leflunomide?

Answer 17

The active metabolite is cleared by hepatic metabolism and biliary secretion, therefore impairment will increase the risk of accumulation.

Question 18

How long should you use contraception for after taking leflunomide?

Answer 18

(M&F) 2 years! - if a washout procedure isn’t carried out

Question 19

If a patient starts having a dry cough, dyspnoea, or thoracic pain and they are on MTX what should happen?

Answer 19

They should STOP and NOT restart!

Question 20

MTX is _________toxic?

Answer 20

Hepatotoxic

Question 21

If a patient on MTX gets skin reactions, what should they do?

Answer 21

Report immediately as this could be a serious allergic reaction.

Question 22

What can be used to improve the side effects of MTX?

Answer 22

Folic acid can be used to improve / correct a toxic effect.

Question 23

What are the common side effects of MTX?

Answer 23

Malaise, fatigue, chills, fever, dizziness, leucopenia, infection, N,V,D, alopecia!
GI side effects - can need to have interruption of treatment or dose reduction!

Question 24

Common side effects of Sulfasalazine?

Answer 24

N/Abdo pain/ D/ V/Stomatitis
Headache, rash, loss of appetite, temp increase, insomnia, tinnitus, leucopenia (reversible)
-Cough/dyspnoea

Question 25

Common side effects with leflunomide?

Answer 25

Mild increased BP, mild allergic reactions, D, N, V, abdo pain, elevation of liver enzymes, headache, dizziness, hair loss, rash, itching dry skin.
Severe liver injury (after first 6 months)
Mild leucopenia!

Question 26

Special precautions when a patient is on MTX?

Answer 26

-Dehydration
-Avoid antifolate drugs ‘trimethoprim’
-Alcohol use - increase hepatotoxicity
-Use folic acid once a week, increased to everyday except MTX day to reduce side effects
-Can have it via SC /IM if GI effects are intolerable!

Question 27

What are the special precautions with sulfasalazine?

Answer 27

-Safest for use in pregnancy - with folic acid
-Enteric coated version licensed in RA
-Do not crush or take with antacids
-Can take NSAIDS alongside
-Can discolour urine orange / yellow or discolour contact lenses orange
-Can cause infertility in men
-Hypoglycaemia

Question 28

What drug slows ‘acetylator status’ and what does this mean?

Answer 28

Sulfasalazine It is taken up and acetylated in the liver. the Acetylated version is renally excreted, if this happens slowly there can be an accumulation of the drug.

Question 29

Special precautions of leflunomide?

Answer 29

*Concurrent hepatotoxic / haematotoxic drugs - increased risk of serious S/E
*Active metabolite hightly protein bound and cleared via hepatic and biliary metabolism
*immunosuppressive

Question 30

What active metabolite has a long half life and is a special precaution when on leflunomide?

Answer 30

A771726 - this can cause adverse reactions even if treatment has stopped. Half life is 1-4 weeks!

Question 31

What monitoring should a patient have on MTX?

Answer 31

FBC, LFT, Renal function.
ONCE stable - every 2-3 months should be checked
-Chest X-ray (pulmonary effects)
-Report signs of infection
-MTX book given

Question 32

What monitoring does a patient on sulfasalazine require?

Answer 32

Before and every other week (for first three months of treatment): FBC and LFT
Every 3 months: FBC and LFT
Renal function: Baseline, Monthly for first 3 months

Question 33

Leflunomide monitoring requirements?

Answer 33

LFT and FBC at initiation and then every 2 weeks during the first 6 months and every 8 weeks thereafter.

Question 34

How long to see an effect with MTX?

Answer 34

Effect seen in 6 weeks to 3 months

Question 35

How long to see an effect with sulfasalazine?

Answer 35

6-8 weeks to 3 months.

Question 36

When can a therapeutic effect be seen with Leflunomide?

Answer 36

4-6 weeks and may improve up to 4-6 months.

Question 37

Can patients on MTX, Leflunomide or Sulfasalazine have live vaccines?

Answer 37

NO

Question 38

What should you do if you miss a dose of MTX?

Answer 38

Take it the following day, do not take the dose if you are three or more days late, in both cases take your dose on the normal day on the following week.

Question 39

How often does someone take MTX?

Answer 39

ONCE a WEEK

Question 40

MOA of Infliximab?

Answer 40

TNFa inhibitor, binds with high affinity to monomers and trimers of soluble TNF and transmembrane TNF and can form complexes of each.
Prevents pro-inflammatory TNF from binding to either one of it’s receptors reducing it’s effect, this can induce other outcomes that reduce TNFs effect on inflammation.

Question 41

What are the outcomes of using Infliximab?

Answer 41

Reduced cytokine and chemokine production, reduced activation and proliferation, inflammatory cell apoptosis, reduced angiogenesis, reduced effects on bone.