Drugs

Question 1

What does allopurinol do? What disorder/ disease is it used to treat?

Answer 1

allopurinol inhibits conversion of purines into uric acid -> Purines remain as xanthine and hypoxanthine (more water soluble than uric acid)
Used to treat Gout

Question 2

What type of drug is Puromycin and how does it work?

Answer 2

-Puromycin is antibiotic that acts as a nucleotide analogue
-Mimic tRNA acceptor region -> allows peptide transfer -> but results in termination of translation
-All about mimicry-> looks like 3’ end of aminoacyl tRNA-> binds at ribosomal A site -> participates in peptide bond formation => peptidyl-puromycin
B/c only has 3’ mimicry -> does not participate in translocation -> dissociates from ribosome shortly after linke to carboxyl terminus of peptide
=> PREMATURE TERMINATION

Question 3

What is α-amanitin and what does it do?

Answer 3

α-amanitin

• Compound from death cap mushroom
• Amanita phalloides is non-competitive inhibitor of RNA pol II -> Binds bridge helix and blocks RNA chain elongation=> prevents translocation
• “constipation” of transcribed RNA that cannot exit cell

Question 4

What is rifampicin and what does it do?

Answer 4

Broad spectrum anti-biotic

• Binds bacterial RNA polymerase and blocks RNA exit channel
• Blocks elongation
• Used in microbacterial TB but resistance is an issue so regulated use as part of multi-pronged tx plan

Question 5

What is AZT used to treat? What does it target?

Answer 5

treats HIV

targets HIV reverse transcriptase

Question 6

What is acyclovir used to treat? What does it target?

Answer 6

Herpes simplex virus
Varicella zoster virus (chickenpox/ shingles)
targes viral DNA polymerase

Question 7

What to quinolones target?

Answer 7

Bacterial DNA gyrase

Question 8

What does tamoxifen treat and how does it work?

Answer 8

Treats breast cancer

Normal: estrogen induces transcritptional activation through estrogen receptor (causes Dimerization of ER -> histone acetylation-> pol II recruitment -> CTD Phosphorylation -> ER/p160 release)

In pathology (ER + breast cancer): Tamoxifen binds ER, prevents recruitment of HATs -> no acetylation of histones -> no recuitment of pol II (may recruit depressors)

Question 9

How does aspirin work?

Answer 9

anti-inflammatory in part because it inhibits the phosphorylation of Inhibitor of NFkB (IkB)-> nuclear localization signal remains hidden -> NFkB cannot enter nucleus and initiate inflammation pathway

Question 10

What do cyclosporine and FK506 do? How do they work?

Answer 10

Immunosuppresants

NF-AT
Phosphorylated in cytoplasm, cannot enter nucleus
-High intracellular Ca -> activates calcineurin’s phosphatase activity -> NF-AT dephosphorylated -> nuclear localization sequence exposed -> goes to nucleus
-In nucleus NF-AT affects transcription of immune response genes & heart function
-
Immunosuppresants (cyclosporine and FK506) -> inhibit calcineurin => inhibit NF-AT from entering nucleus -> no immune response