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Pharmacology (3) > CH1 | Principles of Antimicrobial Therapy > Flashcards

CH1 | Principles of Antimicrobial Therapy Flashcards

1
Q

What is the primary principle that antimicrobial therapy relies on?

A

Antimicrobial therapy takes advantage of the biochemical differences between microorganisms and human beings, resulting in selective toxicity.

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2
Q

Define selective toxicity in the context of antimicrobial therapy.

A

Selective toxicity is the ability of antimicrobial agents to target microorganisms specifically, causing minimal harm to human cells.

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3
Q

What does the term “relative selective toxicity” mean in the context of antimicrobial therapy?

A

It means that the toxicity of the antimicrobial is differential between microbial and host cells, establishing a therapeutic window where pathogen elimination occurs at concentrations that maintain acceptable host tissue safety margins.

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4
Q

What makes selective toxicity possible in antimicrobial therapy?

A

The biochemical differences between microbial cells and human cells.

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5
Q

What are the six factors considered in the selection of the most appropriate antimicrobial agent to use?

A
  1. The identity of the organism.
  2. The susceptibility of the organism to a particular agent.
  3. The site of infection.
  4. The individual factors of the patient receiving the therapy.
  5. The safety and efficacy of the agent.
  6. The cost of the therapy.
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6
Q

What are the most common methods used to identify the microorganism(s) causing an infection?

A
  • Gram stain.
  • Sample culture.
  • DNA.
  • RNA.
  • Antigen detection.
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7
Q

What does the susceptibility of an organism to an antimicrobial agent determine?

A
  • Whether bacteriostatic or bactericidal drugs should be used.
  • The appropriate MIC or MBC.
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8
Q

What does a bactericidal drug do?

A

It kills bacteria.

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9
Q

What does a bacteriostatic drug do?

A

It inhibits bacterial growth.

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10
Q

What is MIC?

A

The minimum concentration that inhibits visible bacterial growth.

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11
Q

What is MBC?

A

The minimum concentration that kills 99.9% of the bacteria.

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12
Q

What structures in tissues act as natural barriers to drug delivery?

A

Capillaries in:
1. The prostate,
2. The testes,
3. The placenta,
4. The vitreous body of the eye,
5. and the CNS.

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13
Q

What role do capillaries in the brain play in drug delivery?

A

They help create and maintain the blood-brain barrier (BBB), restricting drug penetration.

Meningitis increases the permeability of some drugs.

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14
Q

What are the three factors that influence the penetration and concentration of antimicrobial agents in the brain?

A
  1. The lipid solubility of the drug.
  2. The molecular weight of the drug.
  3. The protein binding of the drug.
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15
Q

How does lipid solubility affect drug delivery to the brain?

A

Higher lipid solubility means higher BBB penetration.

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16
Q

How does molecular weight affect drug delivery to the brain?

A

Lower molecular weight results in higher BBB penetration.

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17
Q

How does the protein binding of the drug affect drug delivery to the brain?

A

Lower protein binding of the drug results in higher BBB penetration.

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18
Q

How does the permeability of chloramphenicol and metronidazole compare to beta lactam antibiotics?

A
  • Chloramphenicol and metronidazole both have high lipid-solubility, which results in high BBB penetration.
  • Whereas beta lactams have low lipid solubility, resulting in low BBB penetration.
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19
Q

Why does vancomycin have low BBB permeability?

A

Because of its high molecular weight.

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20
Q

What are the most common patient factors considered when selecting antimicrobial therapy?

A
  1. The state of the immune system (immunocompetent or immunocompromised?).
  2. The presence of renal dysfunction.
  3. The presence of hepatic dysfunction.
  4. The presence of poor perfusion to site of infection.
  5. The patient’s age (affects renal and hepatic elimination processes).
  6. Pregnancy and lactation.
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21
Q

When is empiric therapy used instead of definite therapy?

A

When the patient is critically ill.

22
Q

Define empiric therapy and definite therapy.

A

Empiric therapy refers to the initiation of antimicrobial treatment prior to a definite diagnosis, in contrast to definite therapy, when the invading organism has been identified.

23
Q

What are the common routes of drug administration for antimicrobials?

A

Oral, parenteral, and/or topical administration.

24
Q

What is rational dosing?

A

Rational dosing refers to the design of a drug regimen that ensures optimal therapeutic income.

25
Q

What factors affect the rational dosing of antimicrobial drugs?

A

The pharmacokinetics (ADME) and pharmacodynamics (CDK/TDK/PAE) of the antimicrobial agent.

26
Q

What are the antimicrobial killing patterns that affect the frequency of dosing?

A
  1. Concentration-dependent killing.
  2. Time-dependent killing.
  3. The postantibiotic effect.
27
Q

What is concentration-dependent killing?

A

A property where the antimicrobial’s rate of bacterial killing increases as antibiotic concentration increases from 4-fold to 64-fold the MIC of the drug for the infecting organism.

28
Q

What are examples of drugs that exhibit concentration-dependent killing?

A

Aminoglycosides, and daptomycin.

29
Q

How are drugs that exhibit concentration-dependent killing dosed?

A

Administered as once-a-day bolus infusion: to achieve high peak levels, which favor the rapid killing the infecting pathogen.

30
Q

What is time-dependent killing?

A

A property where the antimicrobial’s rate of bacterial killing is best predicted by the percentage of time that the blood concentrations of the drug remain above the MIC.

31
Q

What are examples of drugs that exhibit time-dependent killing?

A

Beta-lactams, macrolides, and clindamycin.

32
Q

Explain how penicillin is an example of time-dependent killing.

A

For penicillins to provide the most clinical efficacy, their blood levels must be greater than the MIC for 50% of the time. This property is called “time-dependent killing”.

33
Q

What is the postantibiotic effect (PAE)?

A

A property where the antimicrobial’s suppression of microbial growth persists even after the levels of the antibiotic have fallen below the MIC.

34
Q

How are drugs that exhibit the postantibiotic effect dosed?

A

These classes of antibiotic often require only one dose per day due to the postantibiotic effect.

35
Q

What are examples of antibiotics that exhibit the postantibiotic effect?

A

Aminoglycosides and fluoroquinolones.

36
Q

What are the two main categories of chemotherapeutic spectra for antimicrobial drugs?

A
  1. Narrow-spectrum antimicrobial drugs.
  2. Extended- or broad-spectrum antimicrobial drugs.
37
Q

What is the advantage of using narrow-spectrum antimicrobial drugs?

A

They are most specific to the infecting organism, reducing the possibility of superinfections, decreasing the emergence of resistant organisms, and minimizing toxicity. However, Combinations are required in some situations where a single agent is not sufficient.

38
Q

What is an advantage of using combinations of antimicrobial drugs?

A

Synergism, where the combination is more effective than either drug used separately.

39
Q

In which situations is the combination of antimicrobial drugs for synergism recommended?

A

In the treatment of TB, or an infection of unknown origin.

40
Q

What is a disadvantage of combining bactericidal and bacteriostatic drugs?

A

A drug may interfere with the activity of the other drug.

41
Q

How can combination therapy contribute to antibiotic resistance?

A

It can create selection pressure and lead to the development of antibiotic resistance.

42
Q

What defines bacteria as resistant to an antibiotic?

A

Bacteria are considered resistant if the maximal level of the drug that can be tolerated by the host does not halt their growth.

43
Q

What are the two main causes of drug resistance in microorganisms?

A

Naturally inherent resistance and acquired resistance.

44
Q

What are the genetic alterations that can lead to drug resistance?

A

Genetic alterations leading to drug resistance include modification of target sites, decreased accumulation, and enzymatic inactivation.

45
Q

Why do drug-resistant organisms modify target sites?

A

Drug-resistant organisms modify target sites to prevent drugs from binding effectively.

46
Q

What role do porins and efflux pumps play in drug resistance?

A

Porins and efflux pumps decrease drug accumulation in resistant organisms, contributing to drug resistance.

47
Q

What are the most common enzymes that inactive antimicrobials?

A
  1. Beta-lactamases.
  2. Acetyltransferases.
  3. Esterases.
48
Q

Which antimicrobial drugs do beta-lactamases inactivate?

A

Penicillins, cephalosporins, and related drugs.

49
Q

Which antimicrobial drugs do acetyltransferases inactivate?

A

Chloramphenicol, and aminoglycosides.

50
Q

Which antimicrobial drugs do esterases inactivate?

A

Macrolides.

51
Q

What is the purpose of prophylactic use of antibiotics?

A

To prevent infections rather than treat them.

52
Q

When is the prophylactic use of antibiotics considered appropriate?

A

When the benefits outweigh the potential risks such as resistance and superinfections.

Pharmacology (3) (15 decks)

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