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DWT exam 2 > Pharmacology antimicrobials > Flashcards

Pharmacology antimicrobials Flashcards

(59 cards)

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1
Q

Minimum Inhibitory Concentration (MIC)

A

The lowest concentration of drug that inhibits visible bacterial growth
MIC90: concentration for inhibiting 90% of the bacteria

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2
Q

Minimum Bactericidal Concentration (MBC)

A

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

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3
Q

Mutant Prevention Concentration (MPC)

A

The concentration to kill the least susceptible single-step mutant
In theory, kills them all so mutants (ie resistant bacteria) can’t form

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4
Q

bacteriostatic

A

Stop bacteria from multiplying; don’t kill them
* MBC much larger than the MIC (not always able to reach MBC)

Elimination of infection requires host immune response
* Requires an immunocompetent patient

Not as good for
* Sepsis
* Neonates
* Animals on glucocorticoids
* Animals on cancer chemotherapy
* (anything with not great immune system)

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5
Q

bactericidal

A

Kill bacteria if concentrations reach MBC for a certain period of time
* MBC at or near the MIC

Preferred for:
* immunosuppressed animals
* Preferred for severely ill patients
* Sepsis
* Neonates
* Animals on glucocorticoids
* Animals on cancer chemotherapy

Bactericidal antimicrobials are NOT always bactericidal
* Static at concentrations below MBC
* Dose dependent
* Bacteria dependent
* Bacteria must be multiplying for bactericidal antibiotic to work
* Combinations of –static and –cidal???

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6
Q

postantibiotic effect (PAE)

A

Persistent drug effect after plasma concentrations decline below the MIC/MBC

Mechanisms
* Decreased virulence of the bacteria
* Development of abnormal cell wall or septum
* Increased susceptibility to host defenses
* Persistence at sites of infection

Only occurs with some drugs and is bacteria-dependent

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7
Q

pharmokinetic- pharmodynamic interactions

A

Predict the success of antimicrobial therapies
* Relate concentration of drug to MIC of the pathogen
* Vary by class of drug
* Vary with each pathogen

Guidelines for successful treatment:
* Meeting them increases chance of success
* Not meeting them increases chance of failure

“Drug-Bug” Interactions

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8
Q

time dependent antibiotics

A

T>MIC: Duration plasma concentration is above the MIC over 24 hours

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9
Q

concentration dependent antibiotics

A

Cmax:MIC ratio of the maximum plasma concentration (Cmax) to the MIC

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10
Q

concentration/time dependent antibiotics

A

AUC:MIC: ratio of the AUC (area under curve 0-24h) to the MIC

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11
Q

3 main categories of antibiotic mechanism of action

A

cell wall: inhibit synthesis
protein synthesis: inhibit 50s or 30s ribsomal subunit
nucleic acids: inhibit synthesis or function

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12
Q

spectrum of activity

A

Describes the general activity of an antimicrobial
Narrow spectrum
* Implies activity against a limited subset of bacteria

Broad Spectrum
* Implies activity against a wide range of bacteria
* May include mycoplasma, rickettsia, and chlamydia

Tells you that the bacteria CAN BE affected by the antimicrobial
* Individual isolates of bacteria may be resistant to an antimicrobialeven though they are part of its spectrum!

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13
Q

antibacterial spectrum (4 quadrants)

A

Aerobic bacteria
* Gram (+)
* Gram (-)

Anaerobic bacteria
* Gram (+)
* Gram (-)

Broad Spectrum
* Gets all four quadrants
* Gets other categories

Narrow Spectrum
* 1-2/4 quadrants

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14
Q

antibiotic spectrum (6 quadrants)

A

Aerobic bacteria (includes facultatice aerobes)
Gram (+)
* Streptococci
* Staphylococci

Gram (-)
* Respiratory pathogens
* Enteric pathogens

Anaerobic bacteria
* Gram (+)
* Gram (-)

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15
Q

additive/indifferent antimicrobial interaction

A

Typically used to **extend the spectrum **
Does not enhance activity of either

Example:
Horse with pneumonia
Culture – Strep. zooepidemicus (Gm +) and E. coli (Gm -)
Treatment:
Penicillin (for strep) and enrofloxacin (for e coli)

2+2=4

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16
Q

synergistic antimicrobial interaction

A

Synergism – what we hope for
Combination enhances activity
* Trimethoprim / sulfonamide: Static alone; -cidal together
* Ampicillin / clavulanic acid: CA prevents degradation by β-lactamases
* β-lactams and aminoglycosides: β-lactam increases permeability of cell to aminoglycoside

2+2=6

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17
Q

antagonistic antimicrobial interaction

A

Antagonism – what we worry about
Activity of the combination is less than the sum

Example: Static plus Cidal
* Penicillin plus tetracycline

Probably depends on the drug/bug
Not necessarily contraindicated, but avoided when possible

2+2=2

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18
Q

IV route of antibiotics

A
  • Highest concentrations
  • Highest risk for adverse effects
  • Severe systemic illness
  • Owner comfort level/animal temperament
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19
Q

IM/SQ route for antibiotics

A

Bioavailability often complete
* Dehydration/shock may affect absorption

Risk of drug toxicity less than IV
* Injections site reactions

Owner comfort level/animal temperament

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20
Q

oral route for antibiotics

A

Ileus/colitis
Malabsorption
Drug interactions

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21
Q

transdermal route for antibiotics

A

DO NOT GIVE to treat systemic infection

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22
Q

topical route for antibiotics

A

Eyes
Skin
Wounds?
MICs may underestimateactivity of topically/locally applied antibacterial drugs! (MICs are based on plasma concentrations)

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23
Q

site of infections: ISF

A

For most pathogens, the site of infection is the ISF
* Protein binding is major determinant of drug distribution to the ISF
* Low protein bound drugs have good distribution
* Highly protein bound drugs have limited distribution (>80%)

In general, MICs adequately predict success for infections in the ISF

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24
Q

site of infection: protected sites

Study These Flashcards
A

CNS, eye, prostate, bronchus, testes
* Protective barriers that consist of tights junctions between the endothelial cells
* Limited drug movement into these areas
* Lipid solubility or active transport

Significance during inflammation: more able to get to site through increased permeability
MIC testing will overestimate activity of antibiotics!
* need to give higher dose over longer duration

25
intracellular infections
Examples: R. equi, Salmonella sp., Babesia **Lipophilic drugs have better penetration into cells** than do hydrophilic drugs
26
site of infection: abscesses and granulomas
Drug diffusion slow * Lower Cmax * Slower equilibrium **Lower blood supply** to the area **Treatment unsuccessful without DRAINAGE!!!** * If you can DRAIN and LAVAGE the abscess, antibacterials may not be necessary… If you can’t drain: * Choose more lipophilic drugs * Treat for long periods
27
most common bacteria in equine respiratory disease
Streptococcus zooepidemicus
28
most common bacteria in canine skin dz
Staphylococcus pseudintermedius
29
most common bacteria in Feline bacterial cystitis
E. coli
30
beta lactam antibiotics
Penicillins Cephalosporins Carbapenems * Imipenem and meropenem Monobactams * Aztreonam
31
beta lactam antibiotic types
Penicillins Cephalosporins Carbapenems * Imipenem and meropenem Monobactams * Aztreonam
32
beta lactam mechanism of action
Penetrate the outer cell wall Bind to and inhibit **penicillin binding proteins (PBPs)** * Transpeptidase enzymes required for cross-linking of cell wall precursors **Inhibition of cross-linking** * Opens channels through the cell wall to create pores * Allows fluid into the cell, causing cell swelling and death **bactericidal**
33
beta lactams pharmokinetics
Low plasma protein binding * Distribute well to the extracellular fluid in most tissues * Exceptions: cefovecin, ceftiofur **Hydrophilic** * Minimal intracellular concentrations * Do not distribute well to protected sites (CNS, eye, prostate) Metabolism * Minimal * Exceptions: ceftiofur Elimination * Glomerular filtration and tubular secretion * **Very high concentrations in urine!!!** (use for UTI) * 1000x higher than plasma!!! Short half-life and require frequent dosing * Exceptions: cefovecin, ceftiofur crystalline free acid Some **post antibiotic effect (PAE) against gram-positive bacteria** * Penicillin and Streptococci **Time-dependent ** * T>MIC 50% of the dosing interval (Minimum- Some people say 80% for Gm (-)) * If immunosuppressed: T>MIC 90-99%, Constant rate infusions
34
beta lactams plasma protein binding
**Low plasma protein binding** Distribute well to the extracellular fluid in most tissues Exceptions: cefovecin, ceftiofur
35
beta lactams hydrophobic or hydrophilic?
hydrophilic Minimal intracellular concentrations Do not distribute well to protected sites (CNS, eye, prostate)
36
beta lactams metabolism
Minimal Exceptions: ceftiofur
37
beta lactams elimination
Glomerular filtration and tubular secretion Very high concentrations in urine!!! 1000x higher than plasma!!!
38
beta lactam half life
Short half-life and require frequent dosing * Exceptions: cefovecin, ceftiofur crystalline free acid Some PAE against gram-positive bacteria * Penicillin and Streptococci
39
beta lactam time dependency
T>MIC 50% of the dosing interval Minimum- Some people say 80% for Gm (-) If immunosuppressed: T>MIC 90-99%, Constant rate infusions
40
penicillin G
first beta lactam Oral absorption limited * Degraded in gastric acid IV formulations * Potassium or sodium salt * Human products ($$$) IM/SC formulations * Complexed with procaine or benzathine * Longer half-lives and can be dosed less frequently * Veterinary products (cheap)
41
benzylpenicillins
Still effective against * **Streptococcus species** * Anaerobes (Clostridia) * Gram-negative bacteria are usually resistant (E. coli, Klebsiella, Pseudomonas) Inactivated by β-lactamases * Staphylococci +/- * Bacteroides fragilis (anaerobe) Spectrum: Gram-positives, Streptococci, Anaerobes
42
aminopenicillins
Ampicillin, amoxicillin Good oral absorption in small animals * Am**o**xicillin (oral) > ampicillin * Ampicillin more commonly used IV/IM/SC Limited to no oral absorption in large animals Increased spectrum against **gram-negative bacteria** **Lower urinary tract** Still maintain activity against Gram-positives and anaerobes Used VERY frequently in small animals (#1 in cats #2 in dogs)
43
Methicillin (oxacillin) resistant Staph. (MRSA/MRSP)
Bacteria reported resistant to oxacillin should also be considered to be resistant to all other β-lactam antibiotics drugs in methicillin class not used clinically
44
cephalosporin 1st generation
Active against **gram-positive bacteria**, including some beta-lactamase positive staphylococci * Includes cefazolin, cefadroxil and cephalexin **Cefazolin** has the most activity against **gram-negative** bacteria **Cephalexin** (oral) VERY commonly prescribed for dogs for staph pseudointermedius | 1st generation have A in name
45
2nd generation cephalosporins
rarely used in clinical practice
46
3rd generation cephalosporins
Have the **most activity against gram-negative bacteria** Still retain activity against **gram-positives** (but lesser) Not used clinically - injudicious Includes **ceftiofur, cefovecin, cefpodoxime proxetil** * Human drugs * Ceftazidime and cefotaxime – Pseudomonas, CNS infections
47
4th generation cephalosporins
Includes cefepime and cefquinome * **Broad-spectrum** * Cefquinome is currently available in Europe and the UK for veterinary use * Approval for BRD denied by FDA **Rarely used in veterinary medicine** (US) in any species | prob not on test
48
cephalexin
1st gen cephalosporin **Oral use in dogs and cats** FDA approved chewable tablet in dogs (Rilexine®) **Dermatitis** caused by non-methicillin/oxacillin resistant staphylococci
49
cefazolin
cephalosporin 1st generation **IV use in dogs, cats** (sometimes horses) Extralabel use **Surgical prophylaxis*** * Administer within 60 minutes of incision * Dose q90-120 minutes until wound closure
50
Cefpodoxime proxetil
3rd gen cephalosporin Labeled for use in dogs (Has been used safely in cats, foals) **Skin and soft tissue infections** **Longer half-life = Once daily dose** * Better owner compliance **Prodrug** * Ester improves oral absorption | simplicef
51
cefovecin
3rd gen cephalosporin FDA approved for the treatment of **skin infections** in **dogs and cats** **Single subcutaneous dose** (Long half-life due to high affinity protein binding!) Provides therapeutic concentrations for up to **14 days** not fast acting, adverse effects also last 2 weeks | Convenia®
52
ceftiofur
3rd gen cephalosporin FDA approved for use in **(dogs), horses, chickens, turkeys, cattle, goats, sheep and swine** Main cephalosporin used systemically in **large animals** **3rd generation, but…Higher doses needed for Gm-negative bacteria!!!** Three formulations available * Ceftiofur sodium (Naxcel®) powder * Ceftiofur hydrochloride (Excenel®) liquid * Ceftiofur crystalline free acid (Excede®)
53
Ceftiofur crystalline free acid (Excede®)
3rd gen cephalosporin FDA approved for use in **(dogs), horses, chickens, turkeys, cattle, goats, sheep and swine** Main cephalosporin used systemically in **large animals** **3rd generation, but…Higher doses needed for Gm-negative bacteria!!!** **Long-acting:** Long half-life due to extended release formulation! Single **SC dose at the base of the ear in cattle** Single IM dose in swine IM dose in horses, repeated once in 4 days * **Injection site reactions** common!
54
extralabel use of cephalosporins in food animals
**Prohibited by FDA** in major food producing species (Cattle, swine, chickens and turkeys) Exceptions: * Cephapirin: can use for indications not on the label * All other label indications met (dose, route, duration of therapy, etc.) * No prohibition in minor food-producing species (Sheep, goats, honeybees, fish, wildlife, etc.)
55
beta lactam antibiotic adverse effects
Relatively **rare** **Hypersensitivity reactions** (anaphylaxis, IMHA) * Cross-reactivity between penicillins and cephalosporins may exist (15% in people) **At very high concentrations, can inhibit GABA** * Cause CNS excitement and seizures Procaine reactions (reaction to procaine in formulation, not penicillin) * DONT GIVE PROCAINE PENICILLIN IV TO HORSE **Gastrointestinal effects** * Dogs and cats: Vomiting with high oral doses due to irritation of the gastric mucosa * Horses and rabbits: High incidence of antibiotic associated colitis with oral administration
56
beta lactam drug interactions
Aminoglycosides **Synergism!!!** Inactivation!!! * Chemical inactivation when mixed * Does not precipitate Does not happen in vivo * Diluted by plasma
57
methicillin resistance
Mediated via the **MecA gene** Encodes for penicillin binding protein (PBP) 2a Very low binding affinity for all β-lactam antibiotics **resistant to all β-lactams!!!** * Includes carbapenems and monobactams
58
B lactam mechanism of resistance
enzyme degredation- beta lactamases break beta lactam ring ex: staphs
59
b lactamase inhibitors
combine with b lactam antibiotics **blocks b lactamases** **clavulanic acid, sulbactam (not absorbed orally)**, tazobactam ex: clavamox (better choice for staphs)

DWT exam 2 (22 decks)

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