Drugs

Question 1

azidothymidine (AZT)

Answer 1

• Nucleoside analogue of deoxythymidine
• No free 3’OH
• Host kinase phosphorylates it to activate it
• Incorporated into DNA chain via viral reverse transcriptase
• Termination occurs
• Given to HIV patients
• Reduces risk of mother to baby transmission of HIV

Question 2

didanosine

Answer 2

• Nucleoside analogue of deoxyadenosine
• No free 3’OH
• Viral reverse transcriptase incorporates it
• Termination of viral replication
• Has high affinity for reverse transcriptase but low affinity for DNA pol
• Given to HIV patients

Question 3

acyclovir

Answer 3

• Nucleoside analogue of deoxyguanosine
• No free 3’OH
• Converted to monophosphate acyclovir initially via viral kinase
• Only activated in infected cells
• Phosphorylation later via host kinase
• Stop DNA elongation
• Treats Herpes and varicella zoster

Question 4

tenofovir

Answer 4

• nucleotide analogue of deoxyadenosine monophosphate
• No free 3’OH
• Competes with deoxyadenosine
• Initially activated by host kinase
• Lack of 3’OH terminates replication
• Treats HIV

Question 5

cytarabine/vidarabine

Answer 5

• Sugar analogue
• Has 3’OH and 2’OH
• 3’ end accepts elongation
• But 2’OH inhibits addition of next dNTP due to steric hindrance, which stops chain elongation
• Antineoplastic (anti tumor) agent
• Herpes simplex

Question 6

decitabine

Answer 6

• Nucleoside analogue of deoxycytidine
• Hypomethylation agent
• Once incorporated into DNA/RNA – does hypomethylation
• Blocks methylation –> keeps acetyl groupss

Question 7

ciprofloxacin and nalidixic acid

Answer 7

• Antibiotic fluoroquinolone
• Inhibits bacterial DNA gyrase (type II topoisomerase) which is absent in euks
• Leads to positive supercoil buildup, and ultimately chain termination

Question 8

novobiocin

Answer 8

• antibiotic, courmarin family
• Inhibits bacterial DNA gyrase (type II topoisomerase), which is absent in euks
• Leads to positive coil buildup and ultimately, chain termination

Question 9

camptothecin

Answer 9

• Anti-cancer
• Inhibits topoisomerase I activity, which leads to DNA breakage

Question 10

etoposide

Answer 10

• Anti-cancer
• Inhibits the activity of topoisomerase II actvity

Question 11

actinomycin D

Answer 11

• Anti-cancer
• Planar phnoxazone ring intercalates adjacent G-C bases
• Prevents formation of regions of ss DNA
• Prevents RNA transcription as it prevents strand separation
• Inhibitor of replication and transcription

Question 12

rifamycin (rifampin)

Answer 12

• Antibiotic that treats tuberculosis
• Blocks formation of 1st phosphodiester bond by binding to prok RNA pol –> conformation change in RNA pol –> inhibits initiation of transcription

Question 13

diptheria toxin

Answer 13

• Inactivation of EF-2 by ADP ribosylation, which prevents translocation
• Affects protein synthesis and translation

Question 14

streptomycin

Answer 14

• prevents assembly of ribosome (binds to 30S subunit)
• treats bacterial infections

Question 15

tetracyclin

Answer 15

• Interacts with 30S subunit of complete 70S ribosome
  
  • blocks elongation by blocking aminoacyl-tRNA access to A site
• treats bacterial infection

Question 16

erythromycin (macrolide)

Answer 16

• binds to 50S subunit of the complete 70S structure
  
  • blocks ribosome translocation
• treats bacterial infection

Question 17

chloramphenicol

Answer 17

• inhibits peptidyl transferase activity in prokes
• however, at high doses, it can inhibit mitochondrial translation

Question 18

cycloheximide

Answer 18

• Inhibits euk peptidyl transferase activity
  
  • OPPOSITE of chloramphenicol

Question 19

puromycin

Answer 19

• causes premature termination of translation in both prokes and euks by preventing elongation
• structural analog to part of aminoacyl tRNA

Question 20

alpha-aminitin toxin

Answer 20

• found in Death Cap mushroom
• Inhibits RNA pol II in euks and prevents mRNA formation
• Treatment
  
  • GI decontamination
  • penicillin
  • liver transplant

Question 21

colchicine

Answer 21

• prevents polymerization by binding to unpolymerized tubulin molecules
• if given to dividing cells, mitotic spindle breaks down and leads to programmed cell death
• anti-cancer
• Used in treatment of gout
  
  • ​prevents migration of white blood cells to joints

Question 22

taxol

Answer 22

• stabilizes and prevents microtubule disassembly
  
  • preferentially binds tubulin within assembled microtubules
• anti-cancer

Question 23

cytochalasins

Answer 23

• similar to colchicine in microtubules
• prevents actin polymerization
  
  • inhibits cell movement, division and induces apoptosis
• fungal product

Question 24

phalloidin

Answer 24

• similar to taxol in microtubules
• prevents disassembly of actin polymers
  
  • promotes excessive polymerization and inhibits depolymerization
• inhibits cell movement
• toxin from Death Cap mushroom

Question 25

sulfamides/sulfa drugs

Answer 25

* inhibit the folic acid synthesis from PABA to folic acid * inhibit bacterial folate synthesis

Question 26

trimethoprim

Answer 26

* inhibits bacterial dihydrofolate reductase * prevents the production of tetrahydrofolate (THF)

Question 27

methotrexate

Answer 27

* inhibits the function of dihydrofolate reductase * reduces the amount of tetrahydrofolate available for purine synthesis and slows down DNA replication in euks * Anti-cancer

Question 28

hydroxyurea

Answer 28

* inhibits ribonucleotide reductase * prevents ribonucleoside diphosphate from turning into deoxyribonucleoside diphosphate * Anti-cancer

Question 29

allopurinol

Answer 29

* structural analog of hypoxanthine * non-competitive irreversible inhibitor * inhibits xanthine oxidase * decreases the formation of uric acid * used in overproducers

Question 30

febuxostat

Answer 30

* xanthine oxidase inhibitor * febuXOSTat: xanthine oxidase stops

Question 31

5 fluorouracil

Answer 31

* 5 fluorouracil converts to 5 fluoro dUMP and inhibits thymidylase synthase * binds to it irreversibly and inactivates it (suicide inhibitor) * anti-cancer

Question 32

mycophenolic acid

Answer 32

* inhibits formation of GTP from IMP * reversible uncompetitive inhibitor * **_blocks enzyme IMP dehydrogenase_** * deprives rapidly proliferating B and T cells of key components of nucleic acids * used to prevent graft rejections

Question 33

nitroprusside/nitroglycerin

Answer 33

* anti-hypertensive * metabolized by the body to produce NO

Question 34

cholera toxin

Answer 34

* an enzyme that ADP-ribosylates Gαs resulting in **continuously active** Gαs * destroys the intrinsic GTPase activity, which means Gαs is always on * constantly creates cAMP, which leads to dysentery

Question 35

pertussis toxin

Answer 35

* an enzyme that ADP-ribosylates Gαi to make it *continuously inactive* * cAMP increased in respiratory-tract cells * respiratory distress and whooping cough

Question 36

di-isopropyl fluorophosphate (DFP)

Answer 36

* Irreversible inhibitor of acetylcholinesterase * acetylcholinesterase normally cleaves the neurotransmitter acetylcholine in the postsynaptic neuromuscular junction * **at the active site: serine normally forms a covalent bond with the acetyl group during catalysis. DFP blocks this reaction**

Question 37

aspirin

Answer 37

* Aspiring irreversibly inhibits COX in both platelets and endothelial cells * endothelial cells degraded the modified enzyme and synthesize new COX that is fully active * endothelial cells produce prostacyclin, which prevents blood clotting * blood platelets are not able to synthesize new COX and less thromboxane is finally released * thromboxane stimulates blood clotting * **Aspirin is acetyl-salicylic acid and it acetylates a serine in the channel of the active site of COX**

Question 38

statin

Answer 38

* competitive reversible inhibitor * inhibits HMG CoA reductase, the regulated enzyme of cholesterol synthesis.