Nucleic Acid Synthesis Inhibitors Flashcards
Nuclear bases + sugar = __________ + phosphate = __________ = ________
Nucleoside, nucleotide, nucleic acid
DNA replication begins when polymerase enzyme
unwinds and separates the bonds between the two
DNA strands. T or F
False. DNA replication begins when helicase enzyme
unwinds and separates the bonds between the two
DNA strands
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
True
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
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.
What are the 3 classes of nucleic acid inhibitors?
DNA inhibitors
RNA inhibitors
Antifolates (DNA, RNA, Proteins)
Give an example of a first generation quinolone
Nalidixic acid
What is the MOA of quinolones?
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.
What classes of antibiotics fall under DNA inhibitors?
Quinolones, Nitrofurantoin, Nitroimidazoles
Which topoisomerase inhibitors are used as antineoplastic drugs to kill cancer cells?
irinotecan and
etoposide
Give 6 examples of second generation quinolones (fluoroquinolones)
ciprofloxacin, enoxacin,
gatifloxacin, grepafloxacin,
levofloxacin, lomefloxacin,
moxifloxacin, norfloxacin,
ofloxacin, sparfloxacin, and
trovafloxacin
Quinolones are specific inhibitors
of bacterial topoisomerase II. T or F
True
______ and ______ are inhibitors that are effective
against mammalian topoisomerases
irinotecan and
etoposide
Quinolones inhibit the B subunit of DNA gyrase. T or F
False. Quinolones inhibit the A subunit of DNA gyrase
Quinolones are bacteriostatic. T or F
False. The quinolones rapidly inhibits DNA synthesis
and are bactericidal unless growth is prevented
What can nalidixic acid be used to treat?
Urinary tract infections
Nalidixic acid is too toxic for systemic use. T or F
True
________ is indicated for the oral treatment of
urinary tract infections, uncomplicated gonococcal
infections, and prostatitis.
Norfloxacin
_________ 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
Ciprofloxacin
Which antibiotic causes cartilage toxicity and joint swelling in children
Quinolones
Which antibiotic causes Pseudomembranous Colitis due to overgrowth
of Clostridium difficile.
Quinolones
Which antibiotic causes Worsening of
myasthenia gravis
Quinolones
Which antibiotic causes Increased risk of tendonitis & tendon rupture
Quinolones
Give examples of antibiotics that fall under the class nitroimidazole
Benznidazole, metronidazole, nimorazole, ornidazole,
secnidazole, satranidazole, tinidazole,
State the mechanism of action of nitroimidazoles
They generate metabolites that are
incorporated into DNA strands rendering them more prone to
breakage.
Nitroimidazoles are selectively toxic to aerobic organisms,
and can’t affect human cells. T or F
False. These drugs are selectively toxic to anaerobic organisms,
but can affect human cells.
What are nitroimidazoles used to treat?
They are used for amoebiasis, trichomoniasis,
bacteria vaginosis, giardiasis and obligate anaerobic bacteria
infections
Which class of antibiotic leaves a metallic taste and prolonged administration may
cause peripheral neuropathy and seizures
Nitroimidazole
Nitrofurantoin is activated inside bacteria
by reduction via the ____ to
unstable metabolites, which disrupt ribosomal RNA, DNA and
other intracellular components.
flavoprotein nitrofurantoin reductase
Nitrofurantoin is used to treat urinary tract
infections. T or F
True
Which antibiotic causes numbness and pain in your hands and feet?
Nitrofurantoin
Mutations in enzymes may cause quinolone resistance. T or F
True
Mutation of serine or acidic residue decreases the affinity
of drug and enzyme complex. T or F
True
Disruption of the metal ion bridge may
also cause nitroimidazole resistance. T or F
False. Disruption of the metal ion bridge may
also cause quinolone resistance.
Mutations at ______ decrease
catalytic activity while _______ in gyrase and topoisomerase IV does
not affect catalytic activity.
acidic residue, serine residue
Qnr genes that encode ____, ______ and _____ decrease the binding of enzymes to DNA.
proteins
and McbG and MfpA
Thus,
quinolones were protected and these genes (QNR) bind to _____ and _____ and inhibit quinolones from entering into complexes.
gyrase and
topoisomerase
_____ facilitates drug
efflux which leads to resistance
Expression of porins
State the mechanisms of resistance to DNA inhibitors.
- Mutations in enzymes
- Plasmid-mediated quinolone resistance
- Chromosome mediated quinolone resistance
Give 3 examples of RNA synthesis inhibitors
Rifampicin, doxorubicin, actinomycin D
State the mechanism of action of Rifampicin
Rifampicin blocks initiation of RNA synthesis by specifically inhibiting bacterial RNA polymerase.
Rifampicin is specific for
Gram-positive bacteria and some Gram-negative bacteria. T or F
True
Rifampicin does not
interact with mammalian RNA polymerases. T or F
True
Which RNA synthesis inhibitors are used for cancer treatment?
Doxorubicin
and dactinomycin
Rifampicin, Doxorubicin and actinomycin D (dactinomycin) interfere with both
bacterial and mammalian RNA Polymerase. T or F
False. Only doxorubicin and actinomycin D (dactinomycin) interfere with both
bacterial and mammalian RNA Polymerase.
Which RNA synthesis inhibitor causes temporary discolouration of skin and difficulty concentrating?
Rifampicin
Which RNA synthesis inhibitor causes cough or hoarseness accompanied by fever or chills and fast or irregular heartbeat?
Doxorubicin
Which RNA synthesis inhibitor causes hair loss, abdominal swelling and swallowing difficulty?
Dactinomycin
Which antifolates are antibacterials?
Sulphonamides, trimethoprim, proguanil
and pyrimethamine
Which antifolates are anticancer?
methotrexate, pemetrexed
What is the mechanism of action of antifolates?
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.
Proguanil, pyrimethamine and trimethoprim selectively
inhibit folate’s actions in microbial organisms such as bacteria,
protozoa and fungi by inhibiting ______
dihydrofolate reductase
Methotrexate and
pemetrexed inhibit _____
dihydrofolate reductase
Sulphonamides inhibit ______
dihydropteroate synthetase
_______ for
treatment and prophylaxis for Pneumocystis jirovecii pneumonia
Trimethoprim combined with sulfamethoxazole (co-trimoxazole)
Proguanil (_______, _______) and pyrimethamine (_____,
______) are for malaria prophylaxis.
Paludrine, Reludrine, daraprim, metaprim
Pyrimethamine sometimes
combined with sulphadoxine (fansidar, swidar, amalar, maldox) for?
Malaria prophylaxis
Methotrexate and permetrexed
are used as anticancer agents. What else are they used for?
Methotrexate: (osteosarcoma, rheumatoid arthritis)
Permetrexed: (lung carcinoma)
Most antifolates are associated with what side effects?
Steven-Johnson
syndrome, toxic epidermal necrolysis, agranulocytosis and
aplastic anaemia
The use of _______ is strongly contraindicated in pregnancy and
carries significant teratogenic risk
co-trimoxazole
The long-term effectiveness of antifolates is diminished by cellular
response. T or F
True
Because methotrexate is a competitive inhibitor of DHF
reductase, _______ can overcome
the drugs inhibition
increased concentrations of DHF reductase
