DMARD'S Flashcards
What are an example of DMARDS?
Methotrexate, Leflunomide, Ciclosporin
What is the aim of a DMARD?
to halt or reverse the underlying disease itself
MOA methotrexate
Folic acid antagonist with cytotoxic and immunosuppressant activity.
-Can block adenosine uptake
Does methotrexate cross the blood brain barrier?
No, it has low lipid solubility
How is methotrexate taken into cells?
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.
What is Ciclosporin?
Fungal metabolite
-Crosses the gut wall
-Main metabolism Cyp450 = drug interactions
Why is active infection a caution/contraindication to MTX?
Because it is an immunosuppressive drug, can therefore reduce the efficacy of the immune system to fight infection.
Why is Ascities / pleural effusion a caution/contraindication to MTX?
MTX distributed into fluid, accumulates and can be re-excreted to prolong serum half-life increasing the risk o toxicity.
Why significant hepatic impairment / liver disease a caution / contraindication to MTX?
Increased with concomitant hepatotoxic drugs
Why is severe renal impairment a caution / contraindication with MTX?
MTX is renally cleared therefore impairment would lead to accumulation and increased risk of side effects. - Need to stay hydrated.
If someone has renal impairment what should they do with the dose of MTX?
Reduce it.
Is MTX safe in pregnancy?
It is teratogenic!
How long is contraception required in males and female when using MTX?
3-6 months after treatment
Why are the elderly cautioned / contraindicated in MTX?
Reduced folate reserves and reduced renal and hepatic function.
What increases MTX toxicity?
Folate deficiency increases MTX toxicity.
What deficiency can increase the risk of haemolytic anaemia when taking sulfasalazine?
Glucose-6-phosphate dehydrogenase deficiency
Why is having liver impairment a contraindication / caution with leflunomide?
The active metabolite is cleared by hepatic metabolism and biliary secretion, therefore impairment will increase the risk of accumulation.
How long should you use contraception for after taking leflunomide?
(M&F) 2 years! - if a washout procedure isn’t carried out
If a patient starts having a dry cough, dyspnoea, or thoracic pain and they are on MTX what should happen?
They should STOP and NOT restart!
MTX is _________toxic?
Hepatotoxic
If a patient on MTX gets skin reactions, what should they do?
Report immediately as this could be a serious allergic reaction.
What can be used to improve the side effects of MTX?
Folic acid can be used to improve / correct a toxic effect.
What are the common side effects of MTX?
Malaise, fatigue, chills, fever, dizziness, leucopenia, infection, N,V,D, alopecia!
GI side effects - can need to have interruption of treatment or dose reduction!
Common side effects of Sulfasalazine?
N/Abdo pain/ D/ V/Stomatitis
Headache, rash, loss of appetite, temp increase, insomnia, tinnitus, leucopenia (reversible)
-Cough/dyspnoea
Common side effects with leflunomide?
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!
Special precautions when a patient is on MTX?
-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!
What are the special precautions with sulfasalazine?
-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
What drug slows ‘acetylator status’ and what does this mean?
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.
Special precautions of leflunomide?
*Concurrent hepatotoxic / haematotoxic drugs - increased risk of serious S/E
*Active metabolite hightly protein bound and cleared via hepatic and biliary metabolism
*immunosuppressive
What active metabolite has a long half life and is a special precaution when on leflunomide?
A771726 - this can cause adverse reactions even if treatment has stopped. Half life is 1-4 weeks!
What monitoring should a patient have on MTX?
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
What monitoring does a patient on sulfasalazine require?
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
Leflunomide monitoring requirements?
LFT and FBC at initiation and then every 2 weeks during the first 6 months and every 8 weeks thereafter.
How long to see an effect with MTX?
Effect seen in 6 weeks to 3 months
How long to see an effect with sulfasalazine?
6-8 weeks to 3 months.
When can a therapeutic effect be seen with Leflunomide?
4-6 weeks and may improve up to 4-6 months.
Can patients on MTX, Leflunomide or Sulfasalazine have live vaccines?
NO
What should you do if you miss a dose of MTX?
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.
How often does someone take MTX?
ONCE a WEEK
MOA of Infliximab?
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.
What are the outcomes of using Infliximab?
Reduced cytokine and chemokine production, reduced activation and proliferation, inflammatory cell apoptosis, reduced angiogenesis, reduced effects on bone.
