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Flashcards in Drugs Deck (7)
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1
Q

Azathioprine

A

Azathioprine is a prodrug which is converted to 6-mercaptopurine and metabolised to cytotoxic thioguanine nucleotides which are responsible for immunosuppression and inhibiting DNA synthesis.

Both cell-mediated and antibody-mediated immune reactions are depressed.

2
Q

Sirolimus, everolimus

A

Block the third signal

  • Bind FK-BP which inhibits mTOR
  • This blocks third signal vial IL-2 signal transduction
3
Q

Tacrolimus

A

Normally when TCR is activated, increase in intracellular calcium leading to calmodulin activation–>calcineurin activation –>dephosphorylation of NF-AT–>moves to nucleus to act as transcription factor to increase IL-2 production

Tac binds FK-BP which blocks dephosphorylation of NF-AT

4
Q

Cyclosporine

A

Normally when TCR is activated, increase in intracellular calcium leading to calmodulin activation–>calcineurin activation –>dephosphorylation of NF-AT–>moves to nucleus to act as transcription factor to increase IL-2 production

Cyclosporine binds cyclophilin and the complex blocks dephosphorylation of NF-AT

5
Q

Mycophenolate mofetil

A
  • Inhibitor of inosine monophosphate dehydrogenase (IMPDH), which is the rate-limiting enzyme in de novo synthesis of guanosine nucleotides. (T- and B-lymphocytes are more dependent on this pathway than other cell types are.)
  • MPA is a fivefold more potent inhibitor of the type II isoform of IMPDH, which is expressed in activated lymphocytes, than of the type I isoform of IMPDH, which is expressed in most cell types–>therefore a more potent cytostatic effect on lymphocytes than on other cell types.
6
Q

Steroids

A

Glucocorticoid receptors are in cytoplasm in an inactive complex with heat shock proteins. The binding of corticosteroids to the glucocorticoid receptors dissociates heat shock protein from the glucocorticoid receptor. Formed active corticosteroid–glucocorticoid receptor complex migrates to the nucleus and dimerizes on palindromic DNA sequences in many genes. The binding of glucocorticoid receptors in the promoter region of the target genes can lead to either induction or suppression of gene transcripts.

Prevent production of cytokines and vasoactive substances, including interleukin (IL)–1, IL-2, IL-6, tumor necrosis factor-α, chemokines, prostaglandins, major histocompatibility class II, and proteases

7
Q

Methotrexate

A

For cancer: methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate.Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis. Folate is essential for purine and pyrimidine base biosynthesis, so synthesis will be inhibited.

Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins.