Immunosupressants Flashcards
What is DHFR and its function
Dihydrofolate reductase
An enzyme that catalyses the reduction of folic acid to FH4.
FH4 function
Leads to the formation of purines and pyrimidines.
DHFR inhibitors
Methotrexate
What is methotrexate and what does it do
It is an DHFR competitive inhibitor. It works by mimicking folic acid and binding, with a higher affinity, to the active site of the enzyme.
What is the molecular structural difference between folic acid and Methotrexate
Methotrexate differs by an additional amine and methyl group.
TRUE OR FALSE
Methotrexate is a pro-drug
FALSE
Azathiopurine is a pro-drug
TRUE
It is slowly metabolised into 6-mercaptopurine, which is the active anti-inflammatory drug.
TRUE OR FALSE
Leflunomide is a pro-drug
TRUE
It is broken down into Z- and E-Teriflunomide
Which metabolite of Leflunomide provides the most activity
Z-Teriflunomide, although both are active.
What are the essential groups and criteria for SAR in Teriflunomide
- Small lipophilic group at the para position
- Central amide
- Triple bond amine
- Aromatic ring = best activity
Why is a pro-drug used for 6-mercaptopurine
Because 6-mercaptopurine is very quickly metabolised to inactive metabolites;
* 6-Thiouric acid (via Xanthine oxidase)
* Methyl mercaptopurine (via Thiopurine S-methyl transferase)
A pro-drug limits the amount of available 6-mercaptopurine in the body through a slow conversion thereby controlling the metabolisis pathways.
What are NSAIDs contra-indicated by
When should you prescribe NSAIDs with caution/monitoring
Describe the anti-inflammatory drugs that have the highest and lowest risk of a thrombotic event
What increases the risk of a thrombotic event in NSAIDs
COX-2 inhibition has a larger impact on the kidneys which in turn affects the cardiovascular system.
* Increase in BP is commonly seen
* Thrombotic events cautioned (prescribe appropriately)
