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CMOD Block 1 > Antimicrobial Drugs > Flashcards

Antimicrobial Drugs Flashcards

1
Q

Antimicrobial agents act through one of four major mechanisms. Name them.

A
  1. Inhibition of Cell Wall Synthesis
  2. Inhibition of protein synthesis
  3. Inhibition of folic acid biosynthetic pathways
  4. DNA/RNA Synthesis inhibition
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2
Q

Describe synergism and the 3 mechanisms of it.

A

Antibiotic synergism occurs when the effects of a combination of antibiotics is greater than the sum of the effects of the individual antibiotics. 1+1=3.

  1. One drug increases the uptake of another (penicillin/aminoglycosides)
  2. Sequential step blockade for much more complete inhibition of a process - (sulfamethoxazole and trimethoprim)
  3. Protection (B-lactams and B-lactamase inhibitors like amoxicillin and clavulanic acid)
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3
Q

Penicillins belong to what class of antibiotics?

A

B-lactams

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4
Q

Name the 3 broad categories of penicillins.

A

Narrow-spectrum
Broad-spectrum
Aminopenicillins

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5
Q

Describe the MOA of Penicillins.

A

Bind to PBPs, specifically transpeptidase, preventing it from x-linking peptidoglycan molecules. This decreases cell wall integrity, leading to cell lysis.

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6
Q

In general, what type of bacteria is more susceptible to penicillins: Gram + or Gram -?

A

Gram + because they have a thick, highly x-linked cell wall. Gram - bacteria are more resistant because of the protective outer cell membrane (LPS layer)

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7
Q

Are penicillins bactericidal or static?

A

Bacteriocidal

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8
Q

What is the primary mechanism of acquired resistance?

A

Conjugation between bacteria (specifically gram -)

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9
Q

What is the major source of bacterial resistance to penicillins?

A

B-lactamases

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10
Q

What drug/s is/are generally administered synergistically with penicillins to overcome B-lactamase resistance?

A

Clavulanic acid, tazobactam, sulbactam,

All B-lactamase inhibitors that are B-lactams themselves, but have no antimicrobial effect.

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11
Q

Main side effect of penicillin?

A

Hypersensitivity (from rash to anaphylaxis)

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12
Q

What is different regarding the structure of narrow-spectrum antibiotics as opposed to broad?

A

They contain a larger molecule on the penicillin side chain that confers steric hindrance. They can’t twist into other stereoisomers. This makes them less susceptible to B-lactamases but also narrows their spectrum of activity.

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13
Q

Under what circumstances would you treat a person with multiple ANTIBIOTICS? (Not an antibiotic and another drug)

A
  1. Polymicrobial infections
  2. To decrease resistance to one particular drug
  3. Decrease dose-related toxicity
  4. Synergism (enhanced kill tactics)
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14
Q

WHy should you not combine a bactericidal drug with a bacteriostatic drug?

A

Bacteriocidal drugs generally target replicative and growth mechanisms in the bacteria, and a bacteriostatic drug would inhibit growth, rendering the bactericidal drug useless.

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15
Q

Other than bacteriocidal/static combination, what is another example of antagonism by concurrent antimicrobials?

A

A drug may cause increased expression of an enzyme that breaks down the other drug.

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16
Q

What does PAE stand for and what is it?

A

Post-Antibacterial Effect. A drug has PAE if it still has residual effect on the bacteria even after its concentration has subsided.

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17
Q

What general category of drugs have a PAE?

A

DNA/RNA Synthesis inhibitors

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18
Q

Name 2 combinations of B-lactamase inhibitors and the penicillin they are prescribed with.

A

Clavulanic Acid/Amoxicillin

Tazobactam/Piperacillin

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19
Q

Aminopenicillins have greater effect on Gram (-) bacteria than any other penicillin. Why?

A

Gram (-) bacteria are more resistant to penicillin due to their outer membrane. Aminopenicillins have an added amino group, making them more hydrophilic, and able to pass through the LPS membrane and access the cell wall.

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20
Q

Broad spectrum penicillins are modifications of _______________. How are they modified? Why?

A

Aminopenicillins.

Nitrogen and carbon atoms are added to the molecule.

This increases the range of bacteria that are sensitive to the antibiotic.

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21
Q

As the active spectrum of a penicillin increases, the susceptibility to ______________ increases.

A

B-lactamases. More flexible, versatile drugs can bind B-lactamases better than narrow spectrum penicillins with their steric hindrance.

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22
Q

What is the ring of B-lactams called?

A

Thiazolidine ring

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23
Q

What weird group does Atrezonam contain? What is it’s MOA? Is it bactericidal or static?

A

Atrezonam contains a sulfuric acid group. It inhibits bacterial cell wall synthesis by binding to PBPs inside it. It’s Bacteriocidal.

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24
Q

Name the B-lactam groups we studied.

A

Penicillins

Monobactams (Atrezonam)

Carbapenems (Impenem)

Cephalosporins

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25
Q

What B-lactam has the broadest spectrum? What are its 3 advantages over the rest?

A

Impenem

More efficient penetration through bacterial cell wall

Resistance to bacterial enzymes

Affinity for ALL bacterial PBPs.

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26
Q

What is always simultaneously administered with Impenem? Why?

A

Cilastatin. It’s a reversible, competitive inhibitor of DHP-1, an enzyme found in the brush border of the kidneys that breaks down Impenem into toxic metabolites. Cilastatin increases urinary output of Impenem, so there is little to no nephrotoxicity.

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27
Q

How do cephalosporin drugs differ from the penicillins, structurally?

A

6 membered ring attached to the lactam ring rather than the thiazolidine ring of the Penicillins.

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28
Q

Describe the MOA of cephalosporins.

A

Similar to Penicillin (Binds PBPs) but is less susceptible to B-lactamase due to its 6-membered ring structure.

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29
Q

4th generation cephalosporins are reserved for….

A

Severe nosocomial infections with high resistance.

30
Q

Describe the MOA of Vancomycin.

A

Vancomycin is a glycopeptide. It inhibits cell wall synthesis by attaching to the end of peptidoglycan precursor units. (AKA it binds the D-ala/D-ala pair of the pentapeptide chains so they cannot be joined)

31
Q

Why are glycopeptide drugs (Vancomycin) only effective on proliferating/growing bacteria?

A

It attacks cell wall synthesis components.

32
Q

Vancomycin is not effective on Gram - bacteria. Why?

A

ONLY GRAM +.

It is too big to get through the LPS outer membrane in gram - bacteria. Size exclusion based on porin size. (The porin size can shrink as well… mechanism of resistance in gram -)

33
Q

If you have a gram + infection of the kidney, by what route would you administer Vancomycin? Why?

A

IV- for systemic effects.

Why?:

IV- if infection is anywhere other than GI tract

Oral - GI tract infection.

Vancomycin is poorly absorbed from the intestines, and will stay isolated in the intestines if orally administered.

34
Q

If you have C. diff in the colon, what drug can you use to eradicate the bacteria?

A

Vancomycin. Will treat the gram + bacteria and stay isolated in the GI tract.

35
Q

List the inhibitors of Protein Synthesis.

A 
AMINOGLYCOSIDES
Macrolides
Streptogramins
Lincosamides
Oxazolidinones
TETRACYCLINES
36
Q

Name the mechanism(s) of action of aminoglycosides.

A
  1. Irreversibly bind the 30s ribosomal subunit of bacteria.
    At high concentrations, they halt protein synthesis by trapping the ribosome at the AUG start codon.
    At low concentrations, they cause the misreading of mRNA by the ribosome.

2.The polar nature of the drug create fissures and pores in the outer membrane, resulting of leakage of intracellular contents and increased uptake of the drug.

37
Q

True/False: Aminoglycosides are polar.

A

True

38
Q

Aminoglycosides are effective against _____________ bacteria, but not against ____________.

A

Gram (-) but NOT anaerobes.

39
Q

Why are amino glycosides less effective on anaerobes than other bacteria?

A

Anaerobes have less energy available for uptake. Energy is necessary for amino glycosides to penetrate the bacterial cell membrane.

40
Q

Cilastatin is paired with what drug and inhibits what?

A

Paired with the cell wall synthesis inhibitor IMPENEM and blocks DHP-1 from breaking it down in the kidneys.

41
Q

Erythromycin and Azithromycin fall under what category of drugs?

A

Protein synthesis inhibitors, specifically MACROLIDES

42
Q

Macrolides are bacteriostatic/bacteriocidal?

A

Bacteriostatic, but at high concentrations can be bactericidal.

43
Q

Azithromycin works by what MOA?

A

Binds the 50s subunit of bacterial ribosomes and inhibits PEPTIDYL TRANSFERASE, blocking the transfer of the new amino acid into the growing chain.

44
Q

Macrolides are phagocytosed by macrophages. Why is this convenient?

A

Macrophages travel to infection sites.

45
Q

WHat other macrolide binds the 23srNA molecule of the 50S subunit of bacterial ribosomes?

A

Clindamycin (a LINCOSAMIDE)

46
Q

Describe the mechanism of Fosfamycin (another cell wall inhibitor)

A

Fosfamycin prevents the formation of NAM (N-acetylmuramic acid) by inhibiting the enzyme enolpyruvate transferase. Messes up the peptidoglycan subunits.

47
Q

Fosfamycin is usually used to treat what?

A

UTI’s

48
Q

What is the basis for aminoglycoside toxicity?

A

Accumulates in the kidneys

49
Q

What is the drug that must be administered via enteric-coated tablets? Why?

A

Erythromycin. It is easily digested by gastric acid.

50
Q

What is a good inhibitor of bacterial toxin production?

A

Clindamycin (A Lincosamide) specifically, but any inhibitor of bacterial protein synthesis would inhibit the synthesis of toxins. Toxins are proteins.

51
Q

Are tetracyclines bacteriostatic or bactericidal?

A

Bacteriostatic

52
Q

Describe the MOA of tetracyclines.

A

Reversibly bind to the 30s subunit of bacterial ribosomes and inhibit translation of mRNA. Prevents addition of new amino acids to the growing peptide.

53
Q

Do antimicrobial agents that inhibit protein synthesis have a PAE?

A

Some may, depending on their mechanism. MOST DON”T. Most are bacteriostatic. Once the drug concentration has decreased, the bacteria can resume synthesis.

54
Q

Why aren’t mammalian cells affected by tetracycline?

A

Mammalian cells lack the transport mechanism by which bacteria uptake the drug. Tetracycline can only work once it is actively imported into the bacteria, and they have efficient mechanisms for doing so. (effect on anaerobes diminished?)

55
Q

Tetracyclines are primarily prescribed to fight what type of infections?

A

Rickettsias. Rocky mountain spotted fever, lyme, etc..

56
Q

Chloramphenicol works by what mechanism?

A

Protein synthesis inhibition. Binds to the 50S subunit of bacterial ribosomes and blocks peptidyl transferase.

57
Q

What is the danger of giving a MACROLIDE and CHLORAMPHENICOL together?

A

Remember: Macrolides are the erythromycins. They bind the 50 s subunit and block peptidyl transferase as well.

Chloramphenicol and Macrolides work near each other’s site of action and one may impede the action of the other.

EXAMPLE OF ANTAGONISM

58
Q

Name some drugs that interfere with nucleic acid metabolism and intermediary metabolism.

A 
FLOROQUINOLONES
RIFAMYCIN
NITROIMIDAZOLE
DIHYDROFOLATE REDUCTASE INHIBITORS
SULFONAMIDES
59
Q

Describe the MOA of Floroquinolones.

A

Fluoroquinolones bind to and inhibit DNA gyrase. (Topoisomerase II, and IV) They inhibit it AFTER the cutting step, preventing reattachment of the 2 DNA strands.

60
Q

WHy don’t fluoroquinolones affect humans, since we have topoisomerase II and IV as well?

A

Humans have different forms of the enzymes.

61
Q

What kind of drug is Rifamycin?

A

Nucleic acid synthesis inhibitor.

62
Q

Describe the MOA of Rifamycin.

A

Binds to prokaryotic (bacterial) RNA Polymerase. Prevents the INITIATION of RNA synthesis but not its ELONGATION.

63
Q

Describe the selective toxicity of Rifamycin.

A

Humans have different RNA POlymerases so Rifamycin can’t bind them.

64
Q

Rifamycin is highly Lipophilic. Why is this significant? (name 4 reasons)

A

It can easily cross lipophilic membranes.

1- Mycobacterium is susceptible. Mycolic acid is a type of membrane lipid, and Rifamycin diffuses right through it.

  1. Biofilms. The protective coat of biofilms is penetrable by Rifamycin.
  2. High CNS distribution for Bacterial Meningitis infections.
  3. Rifampin can enter phagocytic cells!
65
Q

Rifampin is especially good at intracellular organism destruction, due to its lipophilic nature. It can easily penetrate the membranes. Why is this good for TB?

A

TB is an intracellular pathogen. In order to target the pathogen and evade human cell destruction, rifampin can get inside even phagocytes to reach the TB.

66
Q

How does the drug METRANIDAZOLE work? MOA?

A

Damages DNA by releasing free radicals. The drug is released as a PROdrug that must be REDUCED inside the bacterium by ferredoxin, an enzyme specific to ANAEROBES.

Once reduced by ferredoxin enzymes of an anaerobe, the result is the production of free radicals that damage the bacterial DNA.

67
Q

COTRIMOXAZOLE is a combo of which 2 drugs?How does it inhibit bacteria?

A

Trimethoprim and Sulfamethoxazole.

Dihidrofolate Reductase Inhibitor. –> Interferes with the synthesis of tertrahydrofolic acid.

68
Q

How does the combo of trimethoprim and sulfamethoxazole work?

A

Each drug works on a step in the bacterial synthesis of tetrahydrofolic acid. (folic acid)

Sulfamethoxazole inhibits the incorporation of PABA into folic acid, and trimethoprim prevents the reduction of dehydrofolic acid into tetrahydrofolic acid.

69
Q

Humans have dihydrofolate reductase too. How does cotrimoxazole (trimethoprim/sulfamethoxazole) avoid host toxicity?

A

Mammalian cells use preformed floats (dietary) rather than synthesizing their own.

ALSO, trimethoprim is highly selective to inhibit the dihydrofolate reductase enzymes of LOWER organisms. In order to affect a higher organism, the dosage must increase exponentially.

70
Q

What drug causes the cell membrane to depolarize and lose its membrane potential?

A

DAPTOMYCIN

71
Q

What is the only amino glycoside that we need to really know? Remember: protein synthesis inhibitor. First one we learned about..

A

Gentamycin

CMOD Block 1 (8 decks)

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