iPTX3 EX2 L3 (MEDCHEM ANTIMICROBIALS PT 2 -> FOLATE SYNTH. AND PROTEIN SYNTH.) (CHENG)

T/F: Mammals biosynthesize folic acid.

False

T/F: By blocking folate synthesis in bacteria, we are blocking the synthesis of nucleotides.

True

Three reagents required to form folic acid?

1. Pteridine

2. PABA

3. Glutamic acid

T/F: If folic acid cannot be formed, biosynthesis of methionine, purines, and pyrimidines is impossible in bacteria.

True

Sulfonamides compete with PABA to bind/inhibit where?

Dihydropteroate synthase

Trimethoprim inhibits what enzyme?

dihydrofolate reductase

MOA of sulfaniliamides?

Act as a PABA mimic and inhibits bacterial folic acid synthesis

T/F: In bacteria, antibacterial sulfonamides act as *competitive* inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis.

True

Sulfonamides inhibit (select all that apply)

A. Gram positive bacteria

B. Gram negative bacteria

A. Gram positive bacteria

B. Gram negative bacteria

Why are mammalian cells not affected by sulfanilamides?

Mammalian cells lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate instead.

Sulfa drugs are:

A. Bactericidal

B. Bacteriostatic

B. Bacteriostatic

T/F: Most sulfa drugs are orally bioavailable.

True

Where are sulfa drugs poorly absorbed?

GI tract

Topical sulfa drug example?

Sulfamylone

Advantages of sulfa drugs? (four)

1. Broad spectrum

2. Orally bioavailable

3. Good for UTIs

4. Not highly protein bound, low metabolic concern

Disadvantages of sulfa drugs? (four)

1. Neurological side effects, GI side effects (sufficient)

2. Lower solubility in urine -> crystalluria (kidney damage)

3. Allergies are common

4. Resistance

Which one is a broad-spectrum antibiotic?

A. Penicillin G

B. Vancomycin

C. Sulfa drugs

D. Aminoglycoside

C. Sulfa drugs

What is the mechanism of action of sulfa drugs?

A. Inhibit protein synthesis

B. Inhibit folic acid synthesis

C. Inhibition of cell wall synthesis

D. Disruption of cell membrane structure or function

E. Inhibition of nucleic acid synthesis, structure, or function

B. Inhibit folic acid synthesis

Sulfa drugs compete with _______ to inhibit bacterial folic acid synthesis

A. 6-APA

B. Beta-lactam

C. PABA

D. tRNA

C. PABA

T/F: Trimethoprim alone is bacteriostatic, but in combination with sulfamethoxazole, it is bactericidal.

True

Typically, trimethoprim/sulfamethoxazole is used for the treatment of...

A. Intra-abdominal infections

B. CNS infections

C. Dermatological infections

D. Respiratory infections

D. Respiratory infections

Role of pyrimethamine (Daraprim)?

Antimalarial

Half-life of trimethoprim? Pyrimethamine?

Trimethoprim 11 hours

Pyrimethamine 4-6 days

What is the target of trimethoprim?

A. 30s ribosome

B. Transpeptidase

C. Beta-lactamase

D. Dihydrofolate reductase

D. Dihydrofolate reductase

What is the mechanism of action of co-trimoxazole?

A. Inhibit protein synthesis

B. Inhibit folic acid synthesis

C. Inhibition of cell wall synthesis

D. Disruption of cell membrane structure or function

E. Inhibition of nucleic acid synthesis, structure or function

B. Inhibit folic acid synthesis

Co-trimoxazole is a combination of trimethoprim and ______?

A. Aminoglycoside

B. Penicillins

C. Sulfa drugs

D. Macrolides

C. Sulfa drugs

Function of topoisomerase

Relieving strain in the DNA ahead of the replication fork

T/F Without topoisomerases, DNA cannot replicate normally.

True

How do quinolones block bacterial DNA synthesis?

Inhibiting bacterial topo 2 (gyrase) and topo 4

T/F: The quinolones are a family of synthetic narrow-spectrum antibacterial drugs.

False; broad spectrum.

T/F: Earlier quinolones were only useful in UTIs.

True

What differentiates a quinolone from a fluoroquinolone?

A fluorine atom

T/F: The earlier fluoroquinolones have predominantly gram-negative aerobic activity, but newer ones have improved activity against gram-positive cocci.

True

Which of the fluoroquinolones are least active?

A. Ciprofloxacin

B. Gatifloxacin

C. Levofloxacin

D. Norfloxacin

D. Norfloxacin

Fluoroquinolones belonging to the 2nd generation? (six)

1. Ciprofloxacin

2. Enoxacin

3. Lomefloxacn

4. Levofloxacin

5. Ofloxacin

6. Pefloxacin

T/F: Ciprofloxacin has broad spectrum activity against both gram positive and gram negative bacteria.

True

Oral bioavailability of levofloxacin?

>99%

What is the target of fluoroquinolones?

A. 30s ribosome

B. Transpeptidase

C. DNA topoisomerase

D. Dihydrofolate reductase

C. DNA topoisomerase

What is the mechanism of action of fluoroquinolones?

A. Inhibit protein synthesis

B. Inhibit folic acid synthesis

C. Inhibition of cell wall synthesis

D. Disruption of cell membrane structure or function

E. Inhibition of nucleic acid synthesis, structure or function

E. Inhibition of nucleic acid synthesis, structure, or function

The third-generation quinolones has expanded activity against ___ organisms

A. Gram+ bacteria

B. Gram- bacteria

A. Gram+ bacteria

Nitrofurantoin first-line for the treatment of what

UTIs

Bacterial cells are what percentage protein by dry weight?

50% protein by dry weight

Copying of genetic information from DNA to RNA is called _________

Transcription

Decoding of mRNA into a protein is called __________

translation

Three steps in translation?

1. Initiation

2. Elongation/translocation

3. Termination

T/F: During the initiation step in translation, the larger subunit binds to the tRNA and the amino acids.

True

Action of aminoglycosides at the 30s subunit?

Blocks initiation of translation and causes the misreading of mRNA

Action of tetracyclines at the 30s subunit?

Block the attachment of tRNA to the ribosome

Action of macrolides at the 50s subunit?

Prevent the continuation of protein synthesis

Action of chloramphenicol at the 50s subunit?

Prevents peptide bonds from being formed

Action of lincosamides at the 50s subunit?

Prevent the continuation of protein synthesis

Action of oxazlidinones at the 50s subunit?

Interfere with the initiation of protein synthesis

Action of streptogramins at the 50s subunit?

Each interferes with a distinct step of protein synthesis

T/F: Both actions of aminoglycosides at the 30s subunit (binding to 30s, and blocking formation of initiation complex) lead to mis-incorporation of amino acids.

True

Earliest aminoglycoside?

Streptomycin

Newest generation of aminoglycosides include: (two)

1. Tobramycin

2. Neomycin

Common subunit amongst aminoglycosides?

Amino sugars

Spectrum of activity for aminoglycosides?

Gram negative

NO anaerobic activity

Aminoglycosides are _______

A. Bactericidal

B. Bacteriostatic

A. Bactericidal

T/F: Aminoglycosides synergize well with beta-lactams.

True

T/F: Aminoglycosides have *no* significant post-antibiotic effect.

False; it is significant.

Side-effects associated with aminoglycosides? (two big ones)

1. Ototoxicity

2. Nephrotoxicity

In therapies at higher doses, longer than 5 days, in the elderly, and with renal insufficiency

4 mechanisms of anti-aminoglycoside resistance?

1. Mutation of the ribosomal binding site

2. Decreased uptake of the antibiotic (anaerobic bacteria)

3. Increased expulsion of the antibiotic from the cell

4. Enzymatic modification which break down aminoglycosides

Three types of aminoglycoside modifying enzymes?

1. AAC

2. ANT

3. APH

T/F: Gentamicin is one of the few heat-stable antibiotics.

True

What do we need to combine gentamicin with to treat gram-positive endocarditis?

A cell-wall active antibiotic

Which of the following aminoglycosides is a semisynthetic derivative of kanamycin?

A. Tobramycin

B. Gentamicin

C. Streptomycin

D. Vancomycin

E. Amikacin

E. Amikacin

T/F: Amikacin is resistant to many enzymes which inactivate gentamicin and tobramycin.

True

Why can't aminoglycosides be administered orally?

A. They are very hydrophobic

B. They are sensitive to stomach acid

C. They are sensitive to lactamase

D. They are very polar molecules

D. They are very polar molecules

Which compound acts as a 30s ribosome inhibitor in bacterial protein synthesis?

A. Penicillin G

B. Vancomycin

C. Carbapenem

D. Gentamicin

D. Gentamicin

Which of the following statements about aminoglycosides is FALSE?

A. Includes streptomycin

B. Bind to the 30s ribosomal subunit of the bacterial ribosome

C. It is a broad spectrum antibiotic

D. It can cause ototoxicity

C. It is a broad spectrum antibiotic

Which antibiotic is very effective against gram-negative bacteria?

A. Penicillin G

B. Vancomycin

C. Cephalothin

D. Streptomycin

D. Streptomycin

MOA of tetracyclines?

Bind to 30s subunit and interferes with the attachment of the tRNA carrying amino acids to the ribosome

T/F: Tetracyclines are broad spectrum and low cost.

True

T/F: Tetracyclines are bactericidal.

False; bacteriostatic.

How many rings in doxycycline?

A. 2

B. 3

C. 4

D. 5

C. 4

Which one is a broad-spectrum antibiotic?

A. Penicillin G

B. Vancomycin

C. Tetracycline

D. Aminoglycose

C. Tetracycline

Chloramphenicol is a ______ molecule

A. Small

B. Large

A. Small

T/F: Chloramphenicol is very broad spectrum.

True

T/F: Chloramphenicol is poorly absorbed after oral administration.

False; well absorbed orally.

T/F: Chloramphenicol has excellent BBB penetration.

True

When is chloramphenicol used topically?

Eye infections; penetrates ocular tissues well.

Downside to chloramphenicol?

Very toxic; can cause irreversible damage to bone marrow, aplastic anemia.

Which of the following macrolides it the mother-macrolide (everything else was derived from it)?

A. Clarithromycin

B. Azithromycin

C. Roxithromycin

D. Erythromycin

E. Dirithromycin

D. Erythromycin

T/F: Newer semi-synthetic macrolides such as clarithromycin, azithromycin may have fewer adverse effects.

True

Main structural component of macrolides?

Large macrocyclic lactone ring (containing 14-16 atoms) to which deoxy sugars are attached

Macrolides cover ______

A. Gram-positive

B. Gram-negative

B. Gram negative

Macrolides are ___________

A. Bactericidal

B. Bacteriostatic

B. Bacteriostatic

Clindamycin is ___________

A. Bactericidal

B. Bacteriostatic

B. Bacteriostatic

T/F: Clindamycin has some anaerobic coverage.

True

T/F: Clindamycin is a semisynthetic derivative of lincomycin.

True

T/F: The streptogramins share the same ribosomal binding site as the macrolides and clindamycin (50S).

True

Streptogramins are active against ________

A. Gram positive

B. Gram negative

A. Gram positive

T/F: When streptogramins A and B are used together, they are bacteriostatic; when used on their own, they are bactericidal.

False; when used in conjunction, bactericidal.

MOA of oxazolidinones?

Inhibit protein synthesis by preventing formation of the ribosome complex that initiated protein synthesis

T/F: Linezolid is considered broad-spectrum.

False; narrow-spectrum (only covers some gram-positives).

Where do pleuromutilins bind

50s subunit

Pleuromutilins are generally active against

A. Gram-positive

B. Gram-negative

A. Gram-positive

T/F: Pleuromutilins are unaffected by resistance to other major antibiotic classes, i.e. B-lactams, macrolides, and fluoroquinolones.

True

Which of the following mechanisms can make a bacterium resistant to antibiotics?

A. Chemical modification of the drug

B. Pumping the drug out of the cell

C. Enhancing the binding of the drug to the ribosome

D. A and B

E. A, B, and C

D. A and B