Drugs

Question 1

What is the mechanism of action of methotrexate?

Answer 1

Inhibits dihydrofolate reductase enzyme which usually converts dihyrdofolate to tetrahydrofolate therefore continuously replenishing the cells supply of folates

Question 2

Metabolism of methotrexate?

Answer 2

90% excreted unchanged by the kidneys

small and insignficant amount recycled in the bile

Question 3

Main ADRs of MTX?

Answer 3

GI - nausea, vomiting, mouth ulcers
macrocytosis, bone marrow suppression dose limiting effect
hypersensitivity pneumonitis
hepatotoxicity - raised inflammatory markers
fever
fatigue, headache
alopecia, rash

Question 4

Mechanism of action of leflunomide?

Answer 4

inhibits pyrimidine synthesis

prevents active cells from moving from G1 to S phase

Question 5

ADRs of leflunomide?

Answer 5

Most similar to MTX
*most significant is diarrhoea
in combination with MTX leads to increased pneumonitis, peripheral neuropathy, immune suppression and increased rates of liver impairment

Question 6

Treatment for leflunomide toxicity?

Answer 6

Cholestyramine washout

Question 7

Mechanism of hydroxychloroquine?

Answer 7

blocks TLR pathways of innate immune system preventing innate immune activation

Question 8

Side effects of hydroxychloroquine?

Answer 8

ocular toxicity - corneal depositis and retinopathy, require monitoring
skin changes
GI upset

Question 9

Hydroxychloroquine in pregnancy?

Answer 9

limited data but does reduce amount of congenital heart block in those with Ro/La antibodies
If stopped before conception - high rates of disease flares

Question 10

Examples of TNF inhibitors?

Answer 10

Entanercept - receptor fusion protein
Infliximab - chimeric monoclonal antibody against TNF
Adalimumab - humainsed monoclonal
Golimumab
Certolizumab - fab fragment of humanised monoclonal antibody

Question 11

Examples of IL-1 drugs?

Answer 11

Anakinra

Question 12

Example of IL-6 drugs?

Answer 12

Tocilizumab

Question 13

CTLA-4 fusion protein?

Answer 13

Abatacept