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MEDI2004 Module 3 > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

What are Chemotherapeutic agents?

A
  • Chemical agents used to treat disease
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2
Q

How do Chemotherapeutic agents work?

A
  • They destroy pathogenic microbes or inhibit their growth within the host without doing damage to the host, allowing the immune system to take over the healing process.
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3
Q

what is selective toxicity?

A

The ability of a drug to kill or inhibit a pathogen while damaging the host as little as possible.

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4
Q

Name the General Characteristics of Antimicrobial Drugs

A
  1. Therapeutic Dose
  2. Toxic Dose
  3. Therapeutic Index (TI)
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5
Q

How is the Toxic Index (TI) calculated and what must the number be in order for the drug to be successful?

A

Toxic dose/Therapeutic Dose

Must be >1 for the drug to be used. The larger the number the better the outcome.

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6
Q

What does a low TI mean?

A

A low TI means that although it may be harmful for the bacteria it is also harmful to the host which is not desirable.

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7
Q

Name the properties of Antibacterial Drugs.

A
  • Cidal (kills)
  • Static (inhibits growth)
  • Broad-Spectrum Drugs (attack many different pathogens)
  • Narrow-Spectrum Drugs - Attack only a few different pathogens.
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8
Q

What are the first generations of microorganisms (Genera) that antibiotics are generally coming from

A
  • Streptomyces spp.
  • Micromonospora spp.
  • Bacillus spp.
  • Penicillium spp.
  • Cephalosporum spp.
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9
Q

How do we determine the effectiveness of antimicrobial activity?

A
  1. Minimal Inhibitory Concentration (MIC)

2. Minimal Lethal Concentration (MLC)

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10
Q

What are the MIC and MLC?

A

MIC - The lowest concentration of drug that inhibits growth of a particular pathogen (static)

MLC - The lowest concentration of drug that kills pathogens (cidal)

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11
Q

What are the three techniques routinely used when determining The MIC and MLC?

A
  1. Dilution susceptibility test for MIC
  2. Disk diffusion tests (Kirby Bauer)
  3. The E-test MIC and diffusion
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12
Q

When determining the MIC in a Dilution susceptibility test, what level of turbidity is the MIC?

A

Broth or agar with lowest concentration showing no growth is MIC. If this can be re-cultured in broth again then this is still MIC.

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13
Q

When using the Dilution susceptibility test at which point is the concentration at MLC?

A

If the dose the broth contains has killed all pathogens and the broth shows no Growth when re-cultured this is the MLC.

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14
Q

How does the Disk Diffusion test work?

A
  • Disk impregnated with specific drugs are placed on agar inoculated with test microbe.
  • Drug diffuses from disk into agar, establishing concentration gradient.
  • Observation of clear zones (no growth) around disks shows visible results of which drug works best.
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15
Q

What is the standardized method for carrying out disk diffusion tests?

A

Kirby-Bauer method

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16
Q

when using the Kirby-Bauer method, how is sensitivity/resistance as well as the effective concentration of the drug determined?

A
  • Sensitivity and resistance is determined using tables that relate zone diameter to degree of microbial resistance.
  • Concentration is determined using a Table with plotted values.
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17
Q

In the Disk Diffusion test what are the zones of clearing trying to determine?

A

The level of concentration of the drug that will be effective in the body.

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18
Q

What type of pathogen the E test used for?

A

Convenient for use with anaerobic pathogens.

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19
Q

How does the E Test work?

A
  • Similar to Dis Diffusion method, but uses strip rather than disk.
  • Strips contain gradient of an antibiotic
  • The intersection of the elliptical zone of inhibition with strip indicates MIC
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20
Q

what must the concentration of drug at an infection site be to be effective?

A

> MIC

21
Q

What assays can be used to determine concentration of drug in the blood?

A
  • Microbiological
  • chemical
  • immunological
  • enzymatic
  • chromatographic
22
Q

What are the factors influencing the effectiveness of Antimicrobial Drugs?

A
  1. Ability of drug to reach site of infection.
  2. Susceptibility of pathogen to drug.
  3. Ability of drug to reach concentrations in body that exceed MIC of pathogen.
23
Q

What are the two reasons blood can be excluded?

A
  • Blood clots

- Tissue necrosis

24
Q

The ability of the drug to reach site of infection depends on what factors?

A

The mode of administration:

  • Oral (some drugs destroyed by stomach acid)
  • Topical
  • Parenteral routes (non oral routes of administration)
25
Q

What are the factors influencing the ability of a drug to reach concentrations exceeding MIC

A
  • amount administered
  • route of administration
  • speed of uptake
  • rate of clearance (elimination) from body.
26
Q

How do Mechanisms of Action of Antimicrobial agents work?

A
  • targeting a function necessary for its reproduction or survival.
  • Function needs to be absent from host or substantially different from that of the host.
  • Targeted function is very specific to pathogen (higher therapeutic index)
27
Q

Mechanisms of Antibacterial Drug Action

The things we look for in order for the antimicrobials to work on the affected sites

A
  1. Inhibition of cell wall synthesis
  2. Inhibition of protein synthesis.
  3. Inhibition of nucleic acid synthesis
  4. Metabolic antagonism
28
Q

What is the hierarchy of choosing antimicrobials based on?

A

Which antimicrobials we will used first based on those with a higher therapeutic index due to their mechanisms of antibacterial action

29
Q

What modes of action (sites targeted on cell) do antimicrobials target?

A
  • Cell wall synthesis
  • Folic acid metabolism
  • Cytoplasmic membrane structure
  • RNA elongation
  • DNA gyrase
  • DNA-directed RNA synthesis
  • Protein synthesis (50s, 30s, tRNA)
30
Q

Name the two types of Cell Wall Synthesis Inhibition and what antimicrobials are used for both.

A
  1. Inhibition of normal synthesis of peptidoglycan which causes osmotic lysis.
    - Penicillins and Cephalosporins
  2. Inhibits cell wall synthesis by binding directly to cell wall peptides and blocking transpeptidase enzymes from cross-linking sugar chains.
    - Vancomycin and Teicoplanin (glycopeptide antibiotics)
31
Q

How do Penicillins and Cephalosporins work in regards to cell wall synthesis inhibition.

A
  • Blocks the enzyme that catalyses transpeptidation
    (formation of cross-links in peptidoglycan)
  • prevents cross-linking of sugar chains (NAM and NAG)
  • Prevents the synthesis of coplete cell walls resulting in weak cell wall and leading to lysis of cell.
  • Acts only on growing bacteria that are synthesising new peptidoglycan.
32
Q

What part of the penicillin molecule is cleaved in order to make new variations of penicillin?

A

The 6-APA is cleaved off the R-side chain and then other variants of R-side chain are added to the core 6-APA structure.

33
Q

What is the core structure of the Cephalosporin molecule?

A

7- aminocephalosporic acid

34
Q

How does Protein Synthesis Inhibition work?

A
  • Alter bacterial ribosomes interfering with translation causing faulty protein synthesis.
  • antibiotics will bind specifically to the bacterial ribosomal subunit (50s or 30s)
35
Q

what steps in protein synthesis inhibition will other antibiotics interrupt?

A
  • aminoacyl tRNA binding
  • peptide bond forming
  • mRNA reading
  • translocation
36
Q

What is Translation in terms of Protein Synthesis?

A

The Synthesis of polypeptide directed by sequence of nucleotides in mRNA

37
Q

What are the Ribosomes in terms of Protein synthesis?

A
  • site of translation

- polyribosome - complex of mRNA with several ribosomes

38
Q

In terms of Protein Synthesis Inhibition, what do Aminoglycosides do?

A
  • bind irreversibly to 30s subunit of bacterial ribosome
  • Prevents 50s subunit from attaching to translational initiation complex.
  • Causes misreading of codons leading to insertion of incorrect amino acids.
  • most active against gram negative.
39
Q

In terms of Protein Synthesis Inhibition, what do Tetracyclines do?

A

Bind irreversibly to 30 s subunit leading to distortion and misalignment of tRNA and mRNA.

40
Q

In terms of Protein Synthesis Inhibition, what does Chloramphenicol do?

A
  • bacteriostatic
  • Binds to 50s Subunit
  • Inhibits peptidyl transferase
41
Q

In terms of Protein Synthesis Inhibition, what do Erythromycin and other Macrolides do?

A
  • Bacteriostatic
  • Binds to 50s subunit
  • Inhibits peptide chain elongation during protein synthesis - no new proteins can be made.
42
Q

How do Nucleic Acid Synthesis Inhibition Antibiotics work?

A
  • Blocks DNA replication via inhibition of DNA polymerase and DNA helicase.
  • Blocks transcription of RNA polymerase
43
Q

Why are Nucleic Acid Synthesis Inhibition Antibiotics not as selectively toxic as other antibiotics?

A

Because bacteria and eukaryotes do not differ greatly in the way they synthesize nucleic acids.

44
Q

What is the family of antibiotics used for Nucleic Acid Synthesis Inhibition

A

Quinolones

45
Q

What are the characteristics of Quinolones?

A
  • Broad-spectrum, synthetic containing the 4-quinolone ring
  • Act by inhibiting bacterial DNA-gyrase and topoisomerase II
  • Bacterialcidal, wide range of infections
46
Q

Metabolic Antagonists act as antimetabolites and are structural analogs. How do these characteristics work?

A

Antimetabolites antagonize or block functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes.

Structural analogues are molecules that are structurally similar to and compete with naturally occurring metabolic intermediates. These will block normal cellular metabolism.

47
Q

What drugs are used as a Metabolic Antagonism?

A

Sulphonamides

48
Q

What do Sulphonamides do?

A
  • Block synthesis of folic acid in bacteria ( humans don’t make their own but bacteria do)
  • Folic acid is a cofactor required for production of purines and pyrimidines (TGUA).
  • Used in production of DNA and RNA because host doesn’t produce own folic acid.
  • p-aminobenzoic acid aromatic ring attaches to the folic acid molecular structure which inhibits the metabolic process of the bacteria from producing folic acid.
49
Q

What are the attributes of ideal antimicrobials?

A
  • Solubility in body fluids
  • Selective toxicity
  • Toxicity not easily altered
  • Nonallergenic
  • Stability
  • Resistance not easily acquired
  • Long shelf life
  • Reasonable cost

MEDI2004 Module 3 (2 decks)

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