Lecture 9 & 10: Microbial Control & Antimicrobials Flashcards

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1
Q

What is the use of drugs to treat a disease?

A

Chemotherapy

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2
Q

What interfere with the growth of microbes within a host?

A

Antimicrobial drugs

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3
Q

What are substances produced by a microbe that, in small amounts, inhibits another microbe that are also antimicrobial drugs?

A

Antibiotics

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4
Q

What is a drug that kills harmful microbes without damaging the host?

A

Selective toxicity

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5
Q

What are produced by a microbe and further modified to enhance its function?

A

Semisynthetic antibiotics

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6
Q

What are produced by chemical synthesis to mimic the naturally occurring compounds?

A

Synthetic antibiotics

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7
Q

These are what:

-broad-spectrum
-superinfection
-narrow-spectrum
-bactericidal
-bacteriostatic

A

The actions of antimicrobial drugs

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7
Q

What are against many bacteria, overuse contribute to resistance?

A

Broad-spectrum

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8
Q

What is an infection occurring after or on top of an earlier infection, especially following treatment with broad-spectrum antibiotics?

A

Superinfection

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9
Q

What kills bacteria?

A

Bactericidal

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9
Q

What stops bacteria from reproducing, while not necessarily killing them otherwise?

A

Bacteriostatic

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10
Q

What kill or inhibit limited species of bacteria?

A

Narrow-spectrum

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11
Q

Many types of superinfection have been caused by the overuse of what?

A

Broad-spectrum antibiotics

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12
Q

Which type of antibiotic are more recommended because of its specificity that allows for your body to not be exposed to other types of microbes?

A

Narrow-spectrum antibiotics

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13
Q

Who won the 1908 Nobel Prize for the “magic bullet” - chemicals that could be designed to bind to and kill specific microbes or tumor cells

Arsenic compounds for syphilis patients: Trypan Red for sleeping sickness - killed trypanosomes and another that worked against treponemes

600 derivative compounds tried

A

Paul Ehrlich

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14
Q

Who won the Nobel Prize in 1945 for the 1928 discovery of penicillin, produced by Penicillium

Zone of inhibition: circular area around the spot of the antibiotic in which the bacteria colonies do not grow

A

Alexander Fleming

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15
Q

Who won the Novel Prize in 1939 for Sulfa Drugs – Sulfanilamide?

Red-dye Prontosil converts to sulfanilamide

First antimicrobial agent used to treat wide array of infections

A

Gerhard Domagk

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16
Q

These are:

  1. Inhibition of cell wall synthesis
  2. Inhibition of protein synthesis
  3. Disruption of cell membrane
  4. Inhibition of a metabolic pathway
  5. Inhibition of DNA or RNA synthesis
  6. Inhibition of pathogen attachment
A

Mechanisms of Antimicrobial action

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17
Q

What are the six mechanisms of antimicrobial action?

A
  1. Inhibition of cell wall synthesis
  2. Inhibition of protein synthesis
  3. Disruption of cell membrane
  4. Inhibition of a metabolic pathway
  5. Inhibition of DNA or RNA synthesis
  6. Inhibition of pathogen attachment
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18
Q

Describe penicillin mechanism

A

Penicillin interferes with the linking enzymes, and NAM subunits remain unattached to their neighbors. However, the cell continues to grow as it adds more NAG and NAM subunits. This makes the membrane wall very weak.

The cell bursts from osmotic pressure because the integrity of the peptidoglycan is not maintained

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19
Q

What can cause the inhibition of cell wall synthesis?

A

Most common agents act by preventing cross-linkage of NAM subunits

Most prominent in this group - beta-lactams
-function groups are beta-lactam rings
-Beta-lactams bind to enzymes that
cross-link NAM subunits

Bacteria have weakened cell walls and eventually lyse

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20
Q

Penicillin are effective against what type of organism?

A

Simplest beta-lactams: Aerobic Gram-positive organisms

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21
Q

Penicillinase enzyme breaks down into what?

A

Penicilloic acid

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21
Q

What are the reason bacteria become resistant to penicillin or can do so naturally?

A

They can produce the enzyme Penicillinase

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22
Q

What are the semisynthetic derivatives of beta-lactams?

A

More stable in acidic environments

More readily absorbed

Less susceptible to deactivation

More active against more types of bacteria

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23
Q

What are these:

More stable in acidic environments

More readily absorbed

Less susceptible to deactivation

More active against more types of bacteria

A

Semisynthetic derivatives of beta-lactams

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24
Q

Which generations of Cephalosporins are more effective against gram-negatives?

A

2nd, 3rd, and 4th generations

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25
Q

These are what:

-Vancomycin and cycloserine

-Bacitracin

-Isoniazid and ethambutol

A

Other inhibitors of cell wall synthesis

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26
Q

What interfere with bridges that link NAM subunits in many Gram-positives?

A

Vancomycin and cycloserine

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27
Q

What blocks secretion of NAG and NAM from cytoplasm?

A

Bacitracin

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28
Q

What disrupt formation of mycolic acid in mycobacterial species?

A

Isoniazid and ethambutol

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29
Q

What are the limitations of inhibition of cell wall synthesis?

A

Prevent bacteria from increasing amount of peptidoglycan

Have no effect on existing peptidoglycan layer

Effective only for growing cells

No effect on plant or animal cells; no peptidoglycan

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30
Q

Eukaryotic ribosomes are?

A

80S (40S and 60S)

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30
Q

Prokaryotic ribosomes are?

A

70S (30S and 50S)

31
Q

What are these:

Prevent bacteria from increasing amount of peptidoglycan

Have no effect on existing peptidoglycan layer

Effective only for growing cells

No effect on plant or animal cells; no peptidoglycan

A

The limitations of inhibition of cell wall synthesis

32
Q

What are the inhibitions of protein synthesis?

A

Drugs can selectively target translation

Prokaryotic ribosomes are 70S

Eukaryotic ribosomes are 80S

Mitochondria of animals and humans contain 70S ribosomes; can be harmful

33
Q

What are these:

Drugs can selectively target translation

Prokaryotic ribosomes are 70S

Eukaryotic ribosomes are 80S

Mitochondria of animals and humans contain 70S ribosomes; can be harmful

A

Inhibitions of protein synthesis

34
Q

What is an inhibitor of protein synthesis that is:

broad spectrum
binds to 50S subunit
inhibits peptide bond formation

A

Chloramphenicol

35
Q

What is an inhibitor of protein synthesis that is

broad spectrum
Streptomycin, neomycin, gentamicin
Changes shape of 30S subunit

A

Aminoglycosides

36
Q

What is an inhibitor of protein synthesis that is

broad spectrum
interferes with tRNA attachment

A

Tetracyclines

37
Q

What is an inhibitor of protein synthesis that is

Gram-positives
Binds 50S, prevents translocation

A

Macrolides & Erythromycin

38
Q

What causes the disruption of cytoplasmic membrane?

A

Some drugs become incorporated into cytoplasmic membrane and damage its integrity

Polymyxin
-disrupts cytoplasmic membranes of Gram-negative
-Toxic to human kidneys

Amphotericin B (polyene) attaches to ergosterol found in fungal membranes
-Humans somewhat susceptible because cholesterol similar to ergosterol
-Bacteria lacks sterols; not susceptible

39
Q

Attaches to ergosterol found in fungal membranes
-Humans somewhat susceptible because cholesterol similar to ergosterol
-Bacteria lacks sterols; not susceptible

A

Amphotericin B (polyene) causes the disruption of cytoplasmic membrane

40
Q

When differences exist between metabolic processes of pathogen and host, antimetabolic agents can be effective

A

causes inhibition of metabolic pathways

40
Q

What
-disrupts cytoplasmic membranes of Gram-negative
-Toxic to human kidneys

A

Polymyxin
causes the disruption of cytoplasmic membrane

41
Q

What is an antimetabolite is a chemical that inhibits the use of a metabolite?

A

Metabolic antagonists

42
Q

What are the competitive inhibitors of metabolic pathways?

A

Sulfonamides (Sulfa drugs)
-inhibit folic acid synthesis
-broad spectrum

43
Q

PABA is?

A

Para-aminobenzoic acid

44
Q

PABA is?

A

a starting compound
normally bound to an enzyme with other substrates

45
Q

Trimethoprim inhibits what?

A

inhibits at the second step of metabolic pathways

45
Q

In Sulfonamides mechanism, how do they interact with PABA?

A

It competes with PABA for the active site and PABA will not be able to bind and create dihydrofolic acid and not make DNA and RNA

46
Q

Sulfamethoxazole inhibits what?

A

Inhibits the first step of the metabolic pathway

47
Q

What are the effects of Sulfonamides (Sulfa drugs) that inhibit folic acid synthesis on humans?

A

Since humans obtain folic acid from diet; metabolism is unaffected

48
Q

What can antiviral agents do?

A

Target unique aspects of viral metabolism

49
Q

How does inhibition of nucleic acid synthesis work?

A

Several drugs function by blocking DNA replication or mRNA transcription

Only slight differences between prokaryotic and eukaryotic DNA

50
Q

Why are drugs that inhibit nucleic acid synthesis not normally used to treat infections?

A

Because drugs can affect both types of cells (eukaryotic and prokaryotic) which means human cells can be targeted and harmed

Used in research and perhaps to slow cancer cell replication

51
Q

Why are inhibition of nucleic acid synthesis most often used against viruses?

A

Viral DNA polymerases more likely to incorporate

Viral nucleic acid synthesis more rapid than that in host cells

52
Q

What are the effects on shapes of inhibition of nucleic acid synthesis?

A

Distort shapes of nucleic acid molecules and prevent further replication, transcription, or translation

53
Q

Compounds can interfere with function of nucleic acids (nucleotide analogs)

A

Inhibition of nucleic acid synthesis

54
Q

Effective against rapidly dividing cancer cells

A

Inhibition of nucleic acid synthesis

55
Q

inhibitors of nucleic acicds

A
56
Q

Prevention of virus attachment

Attachment can be blocked by
-peptide and sugar analogs of attachment or receptor proteins (attachment antagonists)

-still in developmental stage

A

Inhibition of pathogen attachment

56
Q

Mechanisms of antimicrobial action

A
57
Q

Readily available
Inexpensive
Chemically stable
Easily administered
Non-toxic and non-allergenic
Selectively toxic against wide range of pathogens

A

Characteristics of an ideal antimicrobial agent

58
Q

Diffusion susceptibility test

A

its a picture

59
Q

If infection is external what drug do you administer?

A

Topical

ointment, liquid solution that is applied on to the outside of the skin

60
Q

What is the type of drug that is the simplest and has

  • lower drug concentrations in blood
  • no reliance on health care provider
  • patients do not always follow prescribing information
A

Oral drugs

61
Q

Oral drugs have these characteristics

A
  • lower drug concentrations in blood because you lose some in digestive tract
  • no reliance on health care provider
  • patients do not always follow prescribing information
62
Q

Drug that requires needle for administration

A

Intramuscular drug

Concentration never as high as IV administration

62
Q

Drug that requires needle or catheter

A

Intravenous drug

Drug concentration diminishes fast as liver and kidneys remove drug from circulation

63
Q

Do you need to know how antimicrobial agent will be distributed to infected tissues?

A

Yes, to know the cause of the problem and how the antimicrobial agent will be distributed in order for you to effectively get the drug to infected tissues

64
Q

What are the three main categories of side effects?

A

Toxicity
Allergies
Disruption of normal microbiota

65
Q

Drug resistant organisms in the population

A

Some organisms are naturally, partially, or completely resistant

Resistance by bacteria acquired in 2 ways
- new mutations of chromosomal genes
- acquisition of R-plasmids via transformation, transduction, and conjugation

66
Q
  • new mutations of chromosomal genes
  • acquisition of R-plasmids via transformation, transduction, and conjugation
A

Resistance by bacteria acquired in 2 ways

67
Q

Tolerance to a usually toxic substance as a result of exposure to a similarly acting substance

A

Cross resistance

67
Q

Multiple resistance and cross resistance

A

Pathogen can require resistance to more than one drug at a time

Common when R-plasmids exchanged

Develop in hospitals and nursing homes; constant use of drugs eliminates sensitive cells

Superbugs

Cross resistance: tolerance to a usually toxic substance as a result of exposure to a similarly acting substance

68
Q

What can be done for drug resistance?

A

High concentrations of drug
- maintained in patient for long enough time

69
Q

Why do we use antimicrobial derivatives? What are the derivatives of Penicillin, cephalosporin, monobactam?

A

to expand the spectrum of activity, improve potency, reduce side effects, and overcome emerging resistance to existing antimicrobial agents. By modifying existing antimicrobials, new versions that are more effective against a wider range of microbes or have better therapeutic properties can be created

they are derived from the original penicillin-G structure, and the derivatives included are penicillin G (benzylpenicillin), penicillin V (phenoxymethylpenicillin), penicillin VK (phenoxymethylpenicillin potassium), and procaine penicillin.

70
Q

What are the limitations of cell wall synthesis inhibitors?

A

Cell wall synthesis inhibitors, like penicillin and vancomycin, have limitations in microbiology mainly due to the emergence of bacterial resistance mechanisms, where bacteria develop ways to evade the antibiotic’s action by altering the target proteins or hindering drug entry, leading to reduced effectiveness against certain bacterial strains, like the Gram-negative bacteria due to their outer membrane barrier. Their activity can be affected by the growth phase of the bacteria, with slower-growing bacteria often exhibiting increased tolerance to these antibiotics.

71
Q

Name examples of metabolic pathways inhibitors and their specific inhibitory actions. What is PABA and how is its activity blocked?

A

Trimethoprim and Sulfamides: often used together as antibiotics and inhibit the synthesis of folic acid, a crucial molecule for bacterial metabolism.

Fluoroquinolones: antibiotics inhibit DNA gyrase, an enzyme essential for bacterial DNA replication, disrupting their cell division.

Penicillin: antibiotic interferes with the synthesis of peptidoglycan, a key component of bacterial cell walls, ultimately leading to cell lysis.

Isoniazid: drug specifically targets the synthesis of mycolic acid, a lipid important for the cell wall of Mycobacterium tuberculosis, making it effective against tuberculosis

72
Q

Name examples of nucleic acid synthesis inhibitors and their specific inhibitory actions

A

fluoroquinolones (ciprofloxacin), rifampicin, and nucleoside analogs (acyclovir), which inhibit bacterial DNA replication by targeting topoisomerases, RNA polymerase, and nucleotide incorporation respectively, thereby disrupting the process of nucleic acid synthesis within the microbial cell.

73
Q

Describe the relative drug concentration in blood when administered by oral vs. intramuscular vs. intravenous routes

A

Oral: lower drug concentrations in blood

Intramuscular: concentration never as high as IV administration

Intravenous: highest drug concentration out of all 3; drug concentration diminishes fast as liver and kidneys remove drug from circulation

74
Q

Describe the routes of drug administration

A

Topical: ointment, liquid solution that is applied on to the outside of the skin

Oral: lower drug concentrations in blood, taken by mouth

Intravenous: requires needle or catheter; drug concentration diminishes fast as liver and kidneys remove drug from circulation

Intramuscular: requires needle; concentration never as high as IV administration