Ch 7 - Antibiotics Flashcards
(180 cards)
1
Q
What does PK stand for in pharmacology?
A
Pharmacokinetics
2
Q
What does PD stand for in pharmacology?
A
Pharmacodynamics
3
Q
Why is it important to consider PK and PD MIC when designing a dose regimen?
A
To ensure effective drug dosing and therapeutic outcomes
4
Q
What are the important PK parameters for time and concentration dependent drugs?
A
Maximum drug concentration and elimination half-life
5
Q
For time-dependent drugs, what is a critical PK parameter?
A
Elimination half-life
6
Q
What is the aim for T>MIC in time-dependent PD index?
A
50-75%
7
Q
What is the exception for T>MIC in carbapenems?
A
25%
8
Q
What is the Cmax/MIC ratio for concentration-dependent PD index?
A
Cmax/MIC ≥ 10
9
Q
What is the AUC/MIC range for concentration-dependent PD index?
A
125 to 250
10
Q
What does MBC stand for?
A
Minimum Bactericidal Concentration
11
Q
What does MPC stand for?
A
Minimum Concentration needed to block growth of less susceptible bacteria
12
Q
What type of drugs target the bacterial cell wall?
A
Beta-Lactam
13
Q
What are the two main types of beta-lactam antibiotics?
A
Penicillins and Cephalosporins
14
Q
What is the origin of natural penicillin?
A
Mold Penicillium
15
Q
What is the significance of the beta-lactam ring in beta-lactam antibiotics?
A
It is the active site for inhibiting bacterial cell wall synthesis
16
Q
What is the effect of the six-member ring in cephalosporins compared to the five-member ring in penicillins?
A
More stable and less susceptible to degradation and resistance
17
Q
What is the mechanism of action for beta-lactams?
A
Interference with bacterial cell wall synthesis
18
Q
What are the key components of the bacterial cell wall that beta-lactams target?
A
Peptidoglycan strands
19
Q
What leads to bacterial cell lysis when affected by beta-lactams?
A
Loss of cell wall rigidity and osmotic pressure
20
Q
What is the relationship between beta-lactams and ribosomal inhibitors?
A
They have well-documented antagonistic effects
21
Q
What is the activity spectrum of natural penicillin G?
A
Effective against gram-positive cocci and some gram-negative anaerobes
22
Q
What type of penicillins are resistant to beta-lactamase?
A
Beta-lactamase-resistant penicillins such as dicloxacillin, cloxacillin, methicillin, and oxacillin
23
Q
What are aminopenicillins?
A
Amoxicillin and ampicillin
24
Q
What is the significance of beta-lactamase inhibitors?
A
They improve the efficacy of beta-lactams against resistant organisms
25
What is the role of carbapenems?
Broad-spectrum antibiotics with resistance to beta-lactamase
26
What is the MOA of carbapenems?
Bind to PBPs and are effective against a wide range of bacteria
27
What is the significance of the mecA gene in MRSA?
It alters the penicillin-binding protein, leading to resistance
28
What are ESBLs?
Extended-Spectrum Beta-Lactamases that confer resistance to certain cephalosporins
29
What is a common challenge in detecting ESBLs?
They may be missed in routine susceptibility testing
30
What is the role of pharmacokinetics in beta-lactam treatment?
Determines absorption, distribution, metabolism, and excretion of the drugs
31
Fill in the blank: Many beta-lactams are _______ bound to plasma proteins.
highly
32
What is the significance of protein binding in beta-lactams?
Prolongs their half-life and duration in circulation
33
What is the elimination route for most beta-lactams?
Primarily via the kidneys
34
What is the Cmax and half-life of amoxicillin at the label dose?
Low Cmax and short half-life increase likelihood of therapeutic failure even with susceptible isolates
35
How do procaine and benzathine penicillin G esters differ in terms of absorption duration?
Procaine lasts 24 hours, benzathine up to 120 hours
36
What is the MIC90 for amoxicillin-clavulanic acid against S. pseudintermedius?
<0.5 μg/mL
37
What is the MIC90 for E. coli?
8 μg/mL
38
What is the protein binding characteristic of imipenem in dogs?
Minimally protein bound
39
What is the clearance rate of imipenem in dogs?
0.26 L/hr/kg
40
What is the preferred administration route for meropenem for faster onset?
Intravenous administration
41
What is the half-life of cefalexin at a 20 mg/kg dose?
5 hours
42
What is the Cmax of cefazolin after a 22 mg/kg IV dose?
178 μg/mL
43
What is the Cmax of cefuroxime after subcutaneous administration in Beagles?
29 μg/mL
44
What is the oral bioavailability of cefpodoxime?
63%
45
What is the protein binding percentage of cefovecin?
96%-98% at low concentrations
46
What is the dosing interval for cefpodoxime to stay above MIC90 for E. coli?
12-24 hours
47
What is the risk associated with combining beta-lactams and bacteriostatic drugs?
Beta-lactams may become bacteriostatic rather than bactericidal
48
Which beta-lactam may not exhibit antagonism with certain Enterobacteriaceae?
Chloramphenicol
49
What is a common side effect of beta-lactam antibiotics?
Diarrhea
50
What may reduce gastrointestinal upset when using amoxicillin-clavulanic acid?
Higher amoxicillin to clavulanic acid ratio
51
What serious condition may arise from overuse of cefovecin?
Emergence of methicillin-resistant Staphylococcus aureus (MRSA)
52
What is the main mechanism of action of vancomycin?
Binding to D-Ala-D-Alanine precursor in bacterial cell walls
53
What type of bacteria is vancomycin primarily used to treat?
Methicillin-resistant Staphylococcus and other Gram-positive bacteria
54
What is a potential toxicity associated with vancomycin?
Nephrotoxicity
55
How does teicoplanin differ from vancomycin?
More lipid-soluble structure
56
What is the spectrum of activity for teicoplanin?
Effective against Gram-positive bacteria
57
What type of bond characterizes fosfomycin?
Carbon–phosphorus bond
58
What is the mechanism of action of the drug similar to vancomycin?
It interferes with bacterial cell wall synthesis by binding to the D-Ala-D-Alanine precursor.
59
What spectrum of bacteria is the drug effective against?
Effective against Gram-positive bacteria, including Staphylococcus, Streptococcus, and some anaerobes.
60
What has largely replaced the clinical role of the drug similar to vancomycin?
Vancomycin and daptomycin due to similar efficacy and better options available.
61
What is fosfomycin?
A phosphonic acid with a carbon–phosphorus bond, produced by Streptomyces fradiae.
62
What is the mechanism of action of fosfomycin?
Inhibits phosphoenolpyruvate transferase, which catalyzes the first step in bacterial cell wall peptidoglycan synthesis.
63
What type of infections is fosfomycin particularly effective for?
Uncomplicated urinary tract infections (UTIs), including those caused by multidrug-resistant E. coli.
64
What is the oral bioavailability of fosfomycin?
30%, with a dose-dependent increase in plasma concentration.
65
What can decrease the bioavailability of fosfomycin?
Food.
66
What is the half-life of fosfomycin?
Short half-life (~1.3 hours).
67
What are common adverse effects of fosfomycin?
Mild gastrointestinal upset, such as diarrhea.
68
What type of drugs are aminoglycosides?
A class of antibiotics that target ribosomes and are bactericidal.
69
Name some aminoglycosides.
* Amikacin
* Gentamicin
* Neomycin
* Tobramycin
* Streptomycin
* Netilmicin
70
What is the structure of aminoglycosides composed of?
Amino sugars linked to an aminocyclitol core.
71
How do aminoglycosides enter gram-negative bacteria?
Through porins in the lipopolysaccharide layer.
72
What ribosomal subunit do aminoglycosides bind to?
30S ribosomal subunit.
73
What type of killing mechanism do aminoglycosides exhibit?
Concentration-dependent killing.
74
What is the recommended dosing strategy for aminoglycosides?
Once daily at high dosages.
75
What type of bacteria are aminoglycosides primarily effective against?
Aerobic gram-negative bacteria and some aerobic gram-positive organisms.
76
What is the synergy effect of aminoglycosides?
Enhances effectiveness when combined with penicillins or vancomycin.
77
What are the common resistance mechanisms to aminoglycosides?
* Enzymatic destruction
* Decreased cell entry
* Altered ribosomal structure
78
What is the most common resistance mechanism to aminoglycosides?
Enzymatic destruction.
79
What is the main adverse effect associated with aminoglycosides?
Nephrotoxicity.
80
What are the risk factors associated with nephrotoxicity from aminoglycosides?
* Hypocalcemia
* Hypomagnesemia
* Dehydration
* Renal diseases
81
What can cause ototoxicity when using aminoglycosides?
Active uptake of the drug into cochlear hair cells.
82
What is a significant pharmacokinetic characteristic of aminoglycosides?
They are poorly absorbed from the GI tract.
83
What is the elimination route for aminoglycosides?
Excretion is proportional to GFR.
84
What can enhance the effectiveness of aminoglycosides in patients with renal disease?
Monitoring serum creatinine levels to adjust dosing intervals.
85
What type of toxicity is associated with aminoglycosides?
Auditory & vestibular toxicity
## Footnote
Aminoglycosides can lead to hearing loss and balance issues due to damage in cochlear hair cells.
86
What is the mechanism of auditory toxicity caused by aminoglycosides?
Active uptake into cochlear hair cells results in cell damage
## Footnote
This mechanism contributes to hearing loss and balance issues.
87
What trough levels of aminoglycosides should be avoided to minimize ototoxicity?
Above 2-5 µg/mL
## Footnote
Higher trough levels are associated with increased risk of ototoxicity.
88
Why should drugs not be used in patients with a perforated eardrum?
Increased risk of ototoxicity
## Footnote
Perforated eardrums can enhance the risk of drug-induced hearing loss.
89
What neuromuscular effects can aminoglycosides have?
Impair calcium release, leading to muscle weakness and respiratory paralysis
## Footnote
Risk increases with intravenous administration, hypocalcemia, or combination with other neuromuscular affecting drugs.
90
What can be used to reverse neuromuscular blockade caused by aminoglycosides?
Cholinesterase inhibitors and calcium
## Footnote
These treatments help restore neuromuscular function.
91
What changes can prolonged therapy or high doses of aminoglycosides cause?
Progressive kidney damage
## Footnote
Kidney damage can be monitored through changes in urine osmolality, creatinine levels, and renal enzyme markers.
92
Which drugs increase the risk of ototoxicity and nephrotoxicity when combined with aminoglycosides?
Other aminoglycosides, NSAIDs, loop diuretics, ACE inhibitors, amphotericin B
## Footnote
These combinations can elevate toxicity risks.
93
What are the primary targets of fluoroquinolones in bacterial cells?
DNA gyrase and topoisomerase IV
## Footnote
These topoisomerases are essential for DNA replication and separation.
94
What is the mechanism of action of fluoroquinolones?
Cause irreversible breaks in bacterial DNA
## Footnote
This action leads to inhibition of DNA replication.
95
What is the significance of the Cmax/MIC ratio for fluoroquinolones?
It should exceed 10 for optimal efficacy
## Footnote
This ratio indicates effective bacterial killing.
96
What are the four generations of fluoroquinolones based on spectrum and potency?
1st: Narrow spectrum, 2nd: Broader spectrum, 3rd: Enhanced potency, 4th: Broadest spectrum
## Footnote
Each generation has different effectiveness against gram-negative and gram-positive bacteria.
97
Which gram-negative bacteria are commonly targeted by fluoroquinolones?
E. coli, Klebsiella, Pasteurella, Pseudomonas spp.
## Footnote
These bacteria are susceptible to fluoroquinolone antibiotics.
98
What is the major mode of resistance to fluoroquinolones?
Mutation in target topoisomerase enzymes
## Footnote
Resistance can also involve reduced drug uptake and increased efflux pump activity.
99
What pharmacokinetic properties do fluoroquinolones exhibit?
Excellent tissue distribution due to lipid solubility
## Footnote
They can accumulate in phagocytic white blood cells and cross the blood-brain barrier.
100
What is the role of pradofloxacin among fluoroquinolones?
Targets P. aeruginosa and many anaerobes
## Footnote
It features a cyclopropyl ring that enhances bacterial killing.
101
What is a key drug interaction concern with fluoroquinolones?
They can inhibit hepatic enzymes, prolonging elimination of other drugs
## Footnote
Notable interactions include theophylline, cyclosporine, and warfarin.
102
What is the effective concentration of fluoroquinolones for pathogens with low MICs?
4.7 μg/mL
## Footnote
This concentration suggests their use is most effective for specific pathogens.
103
What do fluoroquinolones inhibit that can prolong the elimination of other drugs?
Certain hepatic enzymes
## Footnote
This can lead to various drug interactions.
104
Which drug's metabolism can be impaired by fluoroquinolones like ciprofloxacin?
Theophylline
## Footnote
This can lead to toxicity in both dogs and humans.
105
What effect do fluoroquinolones have when combined with cyclosporine?
Increase cyclosporine concentrations
## Footnote
This may necessitate monitoring.
106
What are the potential effects of combining fluoroquinolones with warfarin?
Prolonged anticoagulant effects
## Footnote
This can increase the risk of bleeding.
107
Fill in the blank: Fluoroquinolones may enhance the hypoglycemic effects of _______.
Oral Hypoglycemics and Insulin
108
What type of activity do fluoroquinolones have when given with aminoglycosides?
Synergistic activity
## Footnote
Effective against gram-negative organisms.
109
What CNS effects may occur when fluoroquinolones are combined with drugs that inhibit GABA receptors?
Increased risk of seizures and other CNS disorders
110
What can enrofloxacin cause in terms of glucose readings?
False glucosuria
## Footnote
This can complicate diabetes management.
111
What gastrointestinal issues are associated with fluoroquinolone use?
Vomiting, nausea, and diarrhea
## Footnote
Particularly with oral administration.
112
What cardiovascular toxicity is linked to levofloxacin?
Hypotension and decreased left ventricular function
113
What type of damage can fluoroquinolones like enrofloxacin cause in growing animals?
Cartilage and connective tissue damage
## Footnote
Especially in dogs.
114
What is the risk associated with magnesium in relation to fluoroquinolones?
Magnesium antagonism leading to cartilage damage
115
What can fluoroquinolones inhibit that contributes to seizures?
The release of GABA
116
What retinal issue can occur in cats treated with fluoroquinolones?
Dose-dependent retinal degeneration
## Footnote
Clinical signs may include mydriasis and acute blindness.
117
Which fluoroquinolone is least likely to cause retinal degeneration in cats?
Marbofloxacin
118
What is a potential consequence of impaired bone healing associated with fluoroquinolones?
Impaired fracture healing
119
What can fluoroquinolones induce in certain bacteria, potentially worsening conditions?
Bacteriophage lysis
## Footnote
Examples include S. canis and E. coli.
120
What are fluoroquinolones derived from?
Nalidixic acid
121
What is the primary therapeutic use of fluoroquinolones?
Effective against a wide range of organisms in life-threatening infections
122
What is a concern regarding the use of fluoroquinolones?
Development of antimicrobial resistance
123
What must be monitored to prevent resistance development with fluoroquinolones?
Minimum Bactericidal Concentration (MBC) and mutant prevention concentrations (MPC)
124
What is the mechanism of action of rifampin?
Inhibits the B unit of DNA-dependent RNA polymerase in bacteria
125
Which organisms is rifampin mainly effective against?
Gram-positive organisms
## Footnote
Includes Staphylococcus and Mycobacterium.
126
What is a significant adverse effect associated with rifampin?
GI disturbances and liver function abnormalities
127
What drug interactions are important to consider with rifampin?
Induces microsomal enzymes including CYP450 enzymes
128
What is the mechanism of action of metronidazole?
Inhibits microbial RNA/DNA synthesis via nitrous reduction in anaerobic environments
129
What types of bacteria is metronidazole effective against?
Anaerobic bacteria
## Footnote
Includes B. fragilis and Clostridium spp.
130
What are common adverse effects of metronidazole?
Gastrointestinal upset and CNS toxicity
131
What is the mechanism of action of sulfonamides?
Inhibit bacterial folic acid synthesis by competing with PABA
132
What is the spectrum of activity for sulfonamides?
Broad spectrum but effectiveness varies due to resistance
133
What is a common adverse effect of sulfonamides?
Keratoconjunctivitis sicca
134
What is the mechanism of action for tetracyclines?
Bacteriostatic, concentration dependent
135
Fill in the blank: Tetracyclines are obtained from _______.
Streptomyces
136
What type of activity do tetracyclines exhibit?
Bacteriostatic, concentration dependent
## Footnote
Tetracyclines inhibit bacterial growth without killing bacteria directly.
137
Name three naturally occurring tetracyclines.
* Chlortetracycline
* Oxytetracycline
* Demethylchlortetracycline
## Footnote
These are the foundational tetracyclines from which semisynthetic derivatives are derived.
138
List the classification of tetracyclines by half-life.
* Short-acting: tetracycline, oxytetracycline, chlortetracycline
* Intermediate-acting: demethylchlortetracycline, methacycline
* Long-acting: doxycycline, minocycline
## Footnote
This classification affects the dosing and administration of these drugs.
139
What is the mechanism of action for tetracyclines?
Bind to the 30S ribosomal subunit, preventing the binding of amino-acyl tRNA
## Footnote
This inhibition impairs protein synthesis in bacteria.
140
What is the spectrum of activity for tetracyclines?
Broad-spectrum: effective against gram-positive and gram-negative bacteria, anaerobes, rickettsial organisms, mycoplasma, Chlamydia, Hemobartonella, and spirochetes
## Footnote
However, they are not effective against P. aeruginosa unless specified.
141
True or False: Tetracyclines can be used in immunocompromised patients.
False
## Footnote
Tetracyclines are bacteriostatic and may not be effective in patients with weakened immune systems.
142
What are the main adverse effects of tetracyclines?
* Gastrointestinal upset
* Hepatotoxicity
* Renal toxicity
* Esophageal erosions
* Discoloration of teeth
* Enamel hypoplasia
* Hypersensitivity reactions
* Fanconi-like syndrome
## Footnote
These effects vary by individual and specific tetracycline used.
143
What is the pharmacokinetic profile of doxycycline?
100% bioavailable, penetrates tissues well, including CNS
## Footnote
Doxycycline's bioavailability makes it a preferred choice in many cases.
144
How do tetracyclines interact with cations?
Chelation with cations reduces absorption
## Footnote
Tetracyclines should not be given with antacids, sucralfate, or calcium supplements.
145
What is the mechanism of action for chloramphenicol and florfenicol?
Both bind to the 50S ribosomal subunit, inhibiting peptidyl transferase
## Footnote
This action impairs protein synthesis in bacteria.
146
What are the primary uses for florfenicol?
Approved for bovine respiratory disease and has fewer toxicity concerns compared to chloramphenicol
## Footnote
It is commonly used in small animals, especially cats.
147
What is a notable adverse effect of chloramphenicol?
Bone marrow suppression
## Footnote
This can be reversible or irreversible and is more common in cats.
148
What is the main advantage of florfenicol over chloramphenicol?
Fewer adverse effects and less risk of irreversible bone marrow suppression
## Footnote
This makes florfenicol a safer alternative in many cases.
149
What types of bacteria are lincosamides effective against?
* Aerobic gram-positive cocci
* Nocardia
* Anaerobes
* Cell wall-deficient organisms like Mycoplasma
## Footnote
Clindamycin is more effective than lincomycin, especially against anaerobes.
150
What is a potential side effect of clindamycin?
Pseudomembranous colitis
## Footnote
This condition is caused by an overgrowth of C. difficile due to disruption of normal intestinal microbiota.
151
How do macrolides inhibit bacterial growth?
By binding to the bacterial 50S ribosomal subunit, inhibiting protein synthesis
## Footnote
This can be bacteriostatic or bactericidal depending on the concentration.
152
What are some examples of macrolides?
* Erythromycin
* Azithromycin
* Tylosin
* Tilmicosin
## Footnote
These drugs vary in their specific applications and safety in different animal species.
153
What are the adverse effects associated with erythromycin?
* Gastrointestinal upset
* Cholestatic hepatitis
## Footnote
Gastrointestinal upset can occur in up to 50% of animals treated.
154
What is the role of azithromycin in terms of pharmacokinetics?
Has a large volume of distribution and is well distributed in tissues
## Footnote
Its half-life ranges from 1.5 hours in dogs to 35 hours in humans.
155
What is a significant drug interaction concern with macrolides?
Macrolides can inhibit cytochrome P450 enzymes, increasing drug concentrations
## Footnote
This can lead to toxicity with other medications.
156
What effect do anti-acids have on azithromycin absorption?
Anti-acids extend the absorption of azithromycin
## Footnote
This may influence the effectiveness of the drug.
157
How do macrolides affect cytochrome P450 enzymes?
Macrolides can inhibit cytochrome P450 enzymes, increasing drug concentrations
## Footnote
This can lead to potential drug interactions.
158
Which macrolides are most likely to interact with CYP 3A4?
Azithromycin and clarithromycin
## Footnote
They affect drugs like theophylline, digoxin, and warfarin.
159
What type of effects can occur when azithromycin is combined with other antibiotics?
Synergistic effects
## Footnote
Examples include cefamandole or sulfadiazine/trimethoprim.
160
What is azithromycin used for in cystic fibrosis treatment?
Azithromycin impairs P. aeruginosa adhesion in the respiratory tract
## Footnote
This helps in managing lung infections.
161
What is Tylosin classified as?
Technically classified as a macrolide
## Footnote
It is structurally different from erythromycin.
162
What is the mechanism of action for Tylosin?
Targets the 50S ribosomal subunit
## Footnote
Similar to erythromycin.
163
What is the stability characteristic of Tylosin?
Stable in gastric environment
## Footnote
No need for enteric coating for oral administration.
164
What type of infections is Tylosin used to treat in small animals?
Gastrointestinal infections and bacterial pyodermas
## Footnote
Example includes chronic inflammatory bowel disease.
165
What is the first ketolide approved for human use?
Telithromycin
## Footnote
It is developed for treating respiratory tract infections.
166
What is the mechanism of action for ketolides?
Bind to 50S ribosomal subunit
## Footnote
Similar to macrolides and azalides.
167
What is the primary use of linezolid?
Effective against gram-positive bacteria
## Footnote
Examples include MRSA and vancomycin-resistant enterococci.
168
What is the mechanism of action for oxazolidinones?
Binds to the 50S ribosomal subunit, inhibits protein synthesis at the P site
## Footnote
This action leads to its antibacterial effects.
169
What are the adverse effects associated with linezolid?
Myelosuppression, peripheral neuropathies, and hyperlactatemia
## Footnote
These effects are more common in humans.
170
What is the mechanism of action for daptomycin?
Binds to bacterial cell membranes, causing cell death
## Footnote
This mechanism is specific to gram-positive organisms.
171
What is the main adverse effect of daptomycin in dogs?
Can cause skeletal muscle damage and peripheral neuropathies
## Footnote
Adverse effects are dose-dependent.
172
What class does fusidic acid belong to?
Steroid like antimicrobial
## Footnote
It has a unique mechanism of action.
173
What is the spectrum of activity for fusidic acid?
Primarily gram-positive bacteria
## Footnote
Especially effective against staphylococci.
174
What is the mechanism of action for bacitracin?
Inhibits peptidoglycan synthesis
## Footnote
This action targets gram-positive organisms.
175
What are polymyxins primarily effective against?
Primarily gram-negative organisms
## Footnote
Example includes P. aeruginosa.
176
What is the limitation of using novobiocin systemically?
Systemic toxicity, such as bone marrow suppression
## Footnote
It is used topically only.
177
What is the mechanism of action for mupirocin?
Inhibits incorporation of isoleucine into proteins
## Footnote
It binds to isoleucyl transfer-RNA synthetase.
178
What is the spectrum of activity for silver sulfadiazine?
Effective against P. aeruginosa and broad-spectrum against gram-positive and other gram-negative organisms
## Footnote
Primarily used for burn wounds.
179
What are nitrofurans used for?
Effective against gram-positive and gram-negative organisms, and some protozoa
## Footnote
Examples include nitrofurantoin and furazolidone.
180
What is the mechanism of action for methenamine?
Bactericidal in acidic conditions; bacteriostatic in more alkaline environments
## Footnote
This dual action makes it versatile.
