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Pharmacology 3- Antibacterial agents for systemic therapy Flashcards

1
Q

Minimum Inhibitory Concentration (MIC)

A

The lowest concentration of a drug that INHIBITS the visible bacterial growth

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2
Q

What does MIC90 mean?

A

It will inhibit 90% of bacterial growth

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3
Q

Minimum bactericidal concentration (MBC)

A

The lowest concentration of a drug that kills 99.9% of bacteria

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4
Q

Mutant prevention Concentration (MPC)

A

Such a high concentration killing ALL potential bacteria

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5
Q

What is a bacteriostatic drug?

A
  • Stop bacteria from multiplying but DO NOT kill them.
  • Elimination requires host immune response
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6
Q

What is the relationship of MBC to MIC for a bacteriostatic drug?

A

A bacteriostatic drugs MBC is much larger than the MIC

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7
Q

What kind of patients are bacteriostiatics not okay for and bactericidal good for?

A

ANYONE immunodeficient
- Sepsis
- Neonates
- Animals on glucocorticoids
- Cancer chemotherapy

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8
Q

What is a bactericidal drug?

A

Kill all bacteria if concentrations reach MBC for a certain period of time

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9
Q

What is the relationship of MBC to MIC for a bactericidal drug?

A

The MBC of the drug is at or near the same level of the MIC

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10
Q

Are bactericidal ABX always bactericidal?

A

NO
- Static at concentrations below MBC
- Dose dependent
- Bacteria dependent

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11
Q

What must bacteria be doing for a bactericidal to work?

A

Only kills if replicating
- Some older veterinarians will argue the combination of -static and -cidal

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12
Q

What is the Post-antibiotic effect? (PAE)

A
  • A persistent drug effect
  • Stays in the animal after PLASMA concentration decline below the MIC/MBC
  • Drug is gone but is still working on infection
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13
Q

What are the mechanisms that come from a PAE?

A
  • Decreased virulence of the bacteria
  • Development of abnormal cell wall
  • Increased susceptibility to host defenses
  • Persistence at sites of infection

** Only with come drugs and is bacteria-dependent

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14
Q

What is the drug-bug interaction?

A

Relating of MIC of drug to pathogen
- varies with drug
- varies with pathogen

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15
Q

What is Cmax?

A

Maximum plasma concentration

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16
Q

What is AUC?

A

Area under curve
- Bioavailability over time

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17
Q

What is a time-dependent antibiotic

A

Time > MIC: How long the plasma concentration is above the MIC over a course of 24 hours

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18
Q

What is a concentration-dependent antibiotics?

A

Cmax:MIC
- Cmax ratio to MIC showing if the maximum plasma concentration is reaching the effective levels for MIC

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19
Q

Concentration/Time dependent ABX

A

AUC:MIC
- Ratio of the AUC (over a 24 hour period) to the MIC

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20
Q

What are the three ABX mechanisms of action?

A
  1. Cell Wall
  2. Nucleic Acids
  3. Protein synthesis
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21
Q

ABX Cell Wall mechanism

A

Can
- inhibit synthesis
- inhibit function

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22
Q

ABX Nucleic acid mechanism

A

Can
- inhibit synthesis
- inhibit function

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23
Q

ABX protein synthesis mechanism

A
  • Inhibit 50s: ribosomal subunit
  • Inhibit 30s: ribosomal subunit
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24
Q

What is spectrum of activity?

A

Describes the general activity of an antimicrobial
- Narrow spectrum
- Broad spectrum

*Individual bacterium may be resistant to an antimicrobial even though they are part of the spectrum

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25
Q

What is narrow specturm?

A

Implies activity against a limited subset of bacteria

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26
Q

What is broad spectrum?

A

Implies activity against a wide range of bacteria but doesn’t do it well

27
Q

Antibacterial spectrum 4 quadrants

A
  1. Aerobic GramPOS
  2. Aerobic GramNEG
  3. Anaerobic GramPOS
  4. Anaerobic GramNEG
28
Q

Antibacterial spectrum 4 quadrants- broad spectrum activity

A

Gets all four quadrants

29
Q

Antibacterial spectrum 4 quadrants- intermediate spectrum activity

A

2-3 out of 4 quadrants

30
Q

Antibacterial spectrum 4 quadrants- Narrow spectrum activity

A

1-2 out of 4 quadrants

31
Q

Antibacterial spectrum 6 quadrants

A
  1. Aerobic GramPOS Streptococci
  2. Aerobic GramPOS Staphylococci
  3. Aerobic GramNEG Respiratory pathogens
  4. Aerobic GramNEG Enteric pathogens
  5. Anaerobic GramPOS
  6. Anaerobic GramNEG
32
Q

What is a facultative anaerobe? And how do they fall in the quadrants?

A

With grow with or without O2
- They fall under that category of AEROBES

33
Q

What are the various types of ABX drug interactions?

A
  • Additive
  • Syngerism
  • Antagonism
34
Q

What is an additive drug interaction?

A

Typically two narrow range drugs used together to extend the drug range

** They do not enhance each others activity

35
Q

What is synergism drug interaction?

A

What we want when combining drugs
- Combination enhances activity
- The two drugs are static when alone but become a good level of -cidal when combined

36
Q

What is antagonism drug interaction?

A

what we worry about
- Activity of the combination is less than the sum
- Combining a -static plus a -cidal = try to avoid

37
Q

Main question of judicious use?

A

Is the antibacterial necessary

38
Q

When do we use ABX?

A

Bacterial systemic infection

39
Q

When do we not use ABX?

A
  • Viral infection
  • Fungal infection
  • Parasitic infection
40
Q

When might we use ABX?

A
  • Protozoal infections bacterial infection - locally
41
Q

Important questions for judicious use?

A
  • What is the most appropriate route of administration?
  • Where is the infection?
  • Are there ant local factors that may affect antibiotic efficacy?
42
Q

Factors of IV administration and judicious use

A
  • Used for severe systemic illness
  • High concentrations (100% bioavailability)
  • High risk for adverse effects
43
Q

Factors of IM/SC

A
  • Bioavailability < 100% (Can be affected by dehydration/shock)
  • Less risk of drug toxicity than IV (may lead to injection site reactions)
44
Q

Factors of oral administration and judicious use

A
  • Can lead to colitis
  • Malabsorption
  • Drug interactions (one drug may lower the bioavailability of another)
45
Q

Factors of transdermal administration and judicious use

A

NOT RECOMMENDED
- none ABX formulated for this in veterinary medicine

46
Q

Factors of topical administration and judicious use

A
  • Eyes, skin, wounds
  • MIC of these drugs may be easer to reach than we think because of the high concentration
  • This allows these drugs to overpower bacteria with intermediate susceptibility
47
Q

Factors of inhaled administration and judicious use

A

used for a systemic abx
- Respiratory Dx`

48
Q

Factors of intraarticular regional limb perfusion administration and judicious use

A

Drug administered straight into an articulation
- Good to localize ABX

49
Q

Where is the site of infection for most pathogens?

A

ISF interstitial fluid

50
Q

Site of infection consideration with judicious use

A
  • Protein binding is major determinant of drug distribution into the ISF
51
Q

Low protein bound drugs have ___ distribution

52
Q

High protein bound drugs have ___ distribution

A

limited (with > 80% protein binding)

53
Q

Exceptions to site of infection considerations - protected sites

A

Protected sites:
CNS, eyes, prostate, bronchus, and tested
- Protective barriers consist of tight junctions btwn endothelial cells
- Limited drug movement into these areas
- Need lipid solubility or Active transport mechanisms

54
Q

Significance of inflammation in protected sites and treating with ABX

A

Due to inflammation causing tissue compromise ABX can get into protected sites
- Once inflammation starts to resolve sites become harder to penetrate and ABX becomes less effective

55
Q

Exceptions to site of infection considerations - Intracellular infection

A

Need lipophilic drug to have better penetration into cells

56
Q

Exceptions to site of infection considerations - abscesses and granulomas

A
  • Drug diffuses into sites slowly due to lower blood supply
    – Lower Cmax
    – Slower equilibrium

*Treatment will be unsuccessful without DRAINAGE
- If you cant drain MUST use lipophilic drugs and treat for long periods of time.

57
Q

Exceptions to site of infection considerations - Local tissue factors

A
  • Affect the efficacy of some drugs must clean the sites of the following:
  • Purulent debris
  • Acidic environment
  • Hemoglobin/homorrhage
  • Anaerobic conditions/necrotic tissue
    – decreased blood supply
58
Q

Does MIC take into account local tissue factors

A

NO so you may need to increased amount of drug used if there is a unavoidable local tissue factor

59
Q

Steps to choosing an ABX

A
  • Empiric treatment
  • Choose a drug that is likely to treats that bacteria
    – Availability/formulations
    – Ease of use/Client compliance/Patient compliance
    – Adverse effects
    – Cost
    – Species
60
Q

What is Empiric treatment?

A

Knowing which bacteria commonly cause a disease

61
Q

What bacteria commonly causes equine respiratory dx?

A

Streptococcus zooepidemicus

62
Q

What bacteria commonly causes canine skin dx?

A

Staphylococcus pseudintermedius

63
Q

What bacteria commonly causes feline bacterial cystitis dx?

64
Q

What bacteria commonly causes bovine footrot dx?

A

Fusobacterium necrophorum

DWT (28 decks)

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