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Pharmacology 3- Antibacterial agents for systemic therapy Flashcards

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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
What is narrow specturm?
Implies activity against a limited subset of bacteria
26
What is broad spectrum?
Implies activity against a wide range of bacteria but doesn't do it well
27
Antibacterial spectrum 4 quadrants
1. Aerobic GramPOS 2. Aerobic GramNEG 3. Anaerobic GramPOS 4. Anaerobic GramNEG
28
Antibacterial spectrum 4 quadrants- broad spectrum activity
Gets all four quadrants
29
Antibacterial spectrum 4 quadrants- intermediate spectrum activity
2-3 out of 4 quadrants
30
Antibacterial spectrum 4 quadrants- Narrow spectrum activity
1-2 out of 4 quadrants
31
Antibacterial spectrum 6 quadrants
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
What is a facultative anaerobe? And how do they fall in the quadrants?
With grow with or without O2 - They fall under that category of AEROBES
33
What are the various types of ABX drug interactions?
- Additive - Syngerism - Antagonism
34
What is an additive drug interaction?
Typically two narrow range drugs used together to extend the drug range ** They do not enhance each others activity
35
What is synergism drug interaction?
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
What is antagonism drug interaction?
what we worry about - Activity of the combination is less than the sum - Combining a -static plus a -cidal = try to avoid
37
Main question of judicious use?
Is the antibacterial necessary
38
When do we use ABX?
Bacterial systemic infection
39
When do we not use ABX?
- Viral infection - Fungal infection - Parasitic infection
40
When might we use ABX?
- Protozoal infections bacterial infection - locally
41
Important questions for judicious use?
- What is the most appropriate route of administration? - Where is the infection? - Are there ant local factors that may affect antibiotic efficacy?
42
Factors of IV administration and judicious use
- Used for severe systemic illness - High concentrations (100% bioavailability) - High risk for adverse effects
43
Factors of IM/SC
- Bioavailability < 100% (Can be affected by dehydration/shock) - Less risk of drug toxicity than IV (may lead to injection site reactions)
44
Factors of oral administration and judicious use
- Can lead to colitis - Malabsorption - Drug interactions (one drug may lower the bioavailability of another)
45
Factors of transdermal administration and judicious use
NOT RECOMMENDED - none ABX formulated for this in veterinary medicine
46
Factors of topical administration and judicious use
- 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
Factors of inhaled administration and judicious use
used for a systemic abx - Respiratory Dx`
48
Factors of intraarticular regional limb perfusion administration and judicious use
Drug administered straight into an articulation - Good to localize ABX
49
Where is the site of infection for most pathogens?
ISF interstitial fluid
50
Site of infection consideration with judicious use
- Protein binding is major determinant of drug distribution into the ISF
51
Low protein bound drugs have ___ distribution
good
52
High protein bound drugs have ___ distribution
limited (with > 80% protein binding)
53
Exceptions to site of infection considerations - protected sites
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
Significance of inflammation in protected sites and treating with ABX
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
Exceptions to site of infection considerations - Intracellular infection
Need lipophilic drug to have better penetration into cells
56
Exceptions to site of infection considerations - abscesses and granulomas
- 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
Exceptions to site of infection considerations - Local tissue factors
- 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
Does MIC take into account local tissue factors
NO so you may need to increased amount of drug used if there is a unavoidable local tissue factor
59
Steps to choosing an ABX
- 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
What is Empiric treatment?
Knowing which bacteria commonly cause a disease
61
What bacteria commonly causes equine respiratory dx?
Streptococcus zooepidemicus
62
What bacteria commonly causes canine skin dx?
Staphylococcus pseudintermedius
63
What bacteria commonly causes feline bacterial cystitis dx?
E. Coli
64
What bacteria commonly causes bovine footrot dx?
Fusobacterium necrophorum

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