Nucleic Acid Synthesis Inhibitors

Question 1

Nuclear bases + sugar = __________ + phosphate = __________ = ________

Answer 1

Nucleoside, nucleotide, nucleic acid

Question 2

DNA replication begins when polymerase enzyme
unwinds and separates the bonds between the two
DNA strands. T or F

Answer 2

False. DNA replication begins when helicase enzyme
unwinds and separates the bonds between the two
DNA strands

Question 3

DNA polymerases enzymes make use of a primer to make new DNA by adding nucleotides to a 3’ hydroxyl group on the
primer. T or F

Answer 3

True

Question 4

When nucleotides are added to the 3’ end of the primer or the new DNA strand, a bond is formed between the 3’ phosphate group of the primer/new
DNA and the 5’ hydroxyl group of the nucleotide. T or F

Answer 4

False. When nucleotides are added to the 3’ end of the
primer or the new DNA strand, a bond is formed
between the 3’ hydroxyl group of the primer/new
DNA and the 5’ phosphate group of the nucleotide.

Question 5

What are the 3 classes of nucleic acid inhibitors?

Answer 5

DNA inhibitors

RNA inhibitors

Antifolates (DNA, RNA, Proteins)

Question 6

Give an example of a first generation quinolone

Answer 6

Nalidixic acid

Question 6

What is the MOA of quinolones?

Answer 6

The quinolones inhibit DNA replication during cell division by blocking the action of DNA
gyrase (topoisomerase II), an enzyme responsible for simultaneous unwinding of both strands of DNA during
replication process.

Question 6

What classes of antibiotics fall under DNA inhibitors?

Answer 6

Quinolones, Nitrofurantoin, Nitroimidazoles

Question 6

Which topoisomerase inhibitors are used as antineoplastic drugs to kill cancer cells?

Answer 6

irinotecan and
etoposide

Question 6

Give 6 examples of second generation quinolones (fluoroquinolones)

Answer 6

ciprofloxacin, enoxacin,
gatifloxacin, grepafloxacin,
levofloxacin, lomefloxacin,
moxifloxacin, norfloxacin,
ofloxacin, sparfloxacin, and
trovafloxacin

Question 7

Quinolones are specific inhibitors
of bacterial topoisomerase II. T or F

Answer 7

True

Question 7

______ and ______ are inhibitors that are effective
against mammalian topoisomerases

Answer 7

irinotecan and
etoposide

Question 8

Quinolones inhibit the B subunit of DNA gyrase. T or F

Answer 8

False. Quinolones inhibit the A subunit of DNA gyrase

Question 9

Quinolones are bacteriostatic. T or F

Answer 9

False. The quinolones rapidly inhibits DNA synthesis
and are bactericidal unless growth is prevented

Question 10

What can nalidixic acid be used to treat?

Answer 10

Urinary tract infections

Question 11

Nalidixic acid is too toxic for systemic use. T or F

Answer 11

True

Question 12

________ is indicated for the oral treatment of
urinary tract infections, uncomplicated gonococcal
infections, and prostatitis.

Answer 12

Norfloxacin

Question 13

_________ is approved for use in urinary tract
infections; lower respiratory infections; sinusitis; bone,
joint and skin structure infections; typhoid fever;
urethral and cervical gonococcal infections; and
infectious diarrhea

Answer 13

Ciprofloxacin

Question 14

Which antibiotic causes cartilage toxicity and joint swelling in children

Answer 14

Quinolones

Question 15

Which antibiotic causes Pseudomembranous Colitis due to overgrowth
of Clostridium difficile.

Answer 15

Quinolones

Question 16

Which antibiotic causes Worsening of
myasthenia gravis

Answer 16

Quinolones

Question 17

Which antibiotic causes Increased risk of tendonitis & tendon rupture

Answer 17

Quinolones

Question 18

Give examples of antibiotics that fall under the class nitroimidazole

Answer 18

Benznidazole, metronidazole, nimorazole, ornidazole,
secnidazole, satranidazole, tinidazole,

Question 18

State the mechanism of action of nitroimidazoles

Answer 18

They generate metabolites that are
incorporated into DNA strands rendering them more prone to
breakage.

Question 19

Nitroimidazoles are selectively toxic to aerobic organisms, and can't affect human cells. T or F

Answer 19

False. These drugs are selectively toxic to anaerobic organisms, but can affect human cells.

Question 20

What are nitroimidazoles used to treat?

Answer 20

They are used for amoebiasis, trichomoniasis, bacteria vaginosis, giardiasis and obligate anaerobic bacteria infections

Question 21

Which class of antibiotic leaves a metallic taste and prolonged administration may cause peripheral neuropathy and seizures

Answer 21

Nitroimidazole

Question 22

Nitrofurantoin is activated inside bacteria by reduction via the ____ to unstable metabolites, which disrupt ribosomal RNA, DNA and other intracellular components.

Answer 22

flavoprotein nitrofurantoin reductase

Question 23

Nitrofurantoin is used to treat urinary tract infections. T or F

Answer 23

True

Question 24

Which antibiotic causes numbness and pain in your hands and feet?

Answer 24

Nitrofurantoin

Question 25

Mutations in enzymes may cause quinolone resistance. T or F

Answer 25

True

Question 26

Mutation of serine or acidic residue decreases the affinity of drug and enzyme complex. T or F

Answer 26

True

Question 27

Disruption of the metal ion bridge may also cause nitroimidazole resistance. T or F

Answer 27

False. Disruption of the metal ion bridge may also cause quinolone resistance.

Question 28

Mutations at ______ decrease catalytic activity while _______ in gyrase and topoisomerase IV does not affect catalytic activity.

Answer 28

acidic residue, serine residue

Question 29

Qnr genes that encode ____, ______ and _____ decrease the binding of enzymes to DNA.

Answer 29

proteins and McbG and MfpA

Question 30

Thus, quinolones were protected and these genes (QNR) bind to _____ and _____ and inhibit quinolones from entering into complexes.

Answer 30

gyrase and topoisomerase

Question 31

_____ facilitates drug efflux which leads to resistance

Answer 31

Expression of porins

Question 32

State the mechanisms of resistance to DNA inhibitors.

Answer 32

1. Mutations in enzymes 2. Plasmid-mediated quinolone resistance 3. Chromosome mediated quinolone resistance

Question 33

Give 3 examples of RNA synthesis inhibitors

Answer 33

Rifampicin, doxorubicin, actinomycin D

Question 33

State the mechanism of action of Rifampicin

Answer 33

Rifampicin blocks initiation of RNA synthesis by specifically inhibiting bacterial RNA polymerase.

Question 34

Rifampicin is specific for Gram-positive bacteria and some Gram-negative bacteria. T or F

Answer 34

True

Question 34

Rifampicin does not interact with mammalian RNA polymerases. T or F

Answer 34

True

Question 35

Which RNA synthesis inhibitors are used for cancer treatment?

Answer 35

Doxorubicin and dactinomycin

Question 35

Rifampicin, Doxorubicin and actinomycin D (dactinomycin) interfere with both bacterial and mammalian RNA Polymerase. T or F

Answer 35

False. Only doxorubicin and actinomycin D (dactinomycin) interfere with both bacterial and mammalian RNA Polymerase.

Question 36

Which RNA synthesis inhibitor causes temporary discolouration of skin and difficulty concentrating?

Answer 36

Rifampicin

Question 37

Which RNA synthesis inhibitor causes cough or hoarseness accompanied by fever or chills and fast or irregular heartbeat?

Answer 37

Doxorubicin

Question 38

Which RNA synthesis inhibitor causes hair loss, abdominal swelling and swallowing difficulty?

Answer 38

Dactinomycin

Question 39

Which antifolates are antibacterials?

Answer 39

Sulphonamides, trimethoprim, proguanil and pyrimethamine

Question 40

Which antifolates are anticancer?

Answer 40

methotrexate, pemetrexed

Question 41

What is the mechanism of action of antifolates?

Answer 41

Antifolates indirectly inhibit RNA and DNA synthesis by antagonizing the action of folic acid (vitamin B9) which is a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis, which in turn are required for cell division, DNA/RNA synthesis and repair and protein synthesis.

Question 42

Proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi by inhibiting ______

Answer 42

dihydrofolate reductase

Question 43

Methotrexate and pemetrexed inhibit _____

Answer 43

dihydrofolate reductase

Question 43

Sulphonamides inhibit ______

Answer 43

dihydropteroate synthetase

Question 44

_______ for treatment and prophylaxis for Pneumocystis jirovecii pneumonia

Answer 44

Trimethoprim combined with sulfamethoxazole (co-trimoxazole)

Question 45

Proguanil (_______, _______) and pyrimethamine (_____, ______) are for malaria prophylaxis.

Answer 45

Paludrine, Reludrine, daraprim, metaprim

Question 46

Pyrimethamine sometimes combined with sulphadoxine (fansidar, swidar, amalar, maldox) for?

Answer 46

Malaria prophylaxis

Question 47

Methotrexate and permetrexed are used as anticancer agents. What else are they used for?

Answer 47

Methotrexate: (osteosarcoma, rheumatoid arthritis) Permetrexed: (lung carcinoma)

Question 48

Most antifolates are associated with what side effects?

Answer 48

Steven-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis and aplastic anaemia

Question 49

The use of _______ is strongly contraindicated in pregnancy and carries significant teratogenic risk

Answer 49

co-trimoxazole

Question 50

The long-term effectiveness of antifolates is diminished by cellular response. T or F

Answer 50

True

Question 51

Because methotrexate is a competitive inhibitor of DHF reductase, _______ can overcome the drugs inhibition

Answer 51

increased concentrations of DHF reductase