Fall '13 Quiz 2 Flashcards
1
Q
What is the suffix for fluoroquinolones drugs?
A
“-floxacins”
2
Q
What was the first veterinary fluoroquinolone?
A
Enrofloxacin
3
Q
What does Enrofloxacin turn into after hepatic metabolism?
A
Ciprofloxacin
4
Q
What was the first quinolone drug that fluoroquinolones are based on?
A
Nalidixic acid
5
Q
What are regular fluoroquinolones’ method of action?
A
Inhibit DNA gyrase
relaxes supercoiled DNA
6
Q
Inhibition of DNA gyrase effects which type of bacteria?
A
Gram negative coliforms
7
Q
What are advanced fluoroquinolones’ method of action?
A
Inhibit Topoisomerase IV
separates replicated DNA during cell division
8
Q
Inhibition of Topoisomerase IV effects which type of bacteria?
A
Gram positive
9
Q
Are fluoroquinolones -cidal or -static?
A
-cidal
10
Q
What happens when fluoroquinolones inhibit these enzymes?
A
Stabilizes the enzyme-DNA complex
= breaks DNA
= triggers apoptosis
11
Q
What is a first generation fluoroquinolone? What is it effective against?
A
Nalidixic acid (no F- atom)
Gram negative bacteria
Urinary tract only
12
Q
What is a second generation fluoroquinolone? What is it effective against?
A
Enrofloxacin
Mostly Gram negative bacteria
Some Gram positive bacteria
13
Q
What is a third generation fluoroquinolone? What is it effective against?
A
Pradofloxacin
Gram negative bacteria
More Gram positive bacteria
14
Q
What generation of fluoroquinolones has the broadest spectrum of activity?
A
Third
Pradofloxacin
15
Q
What type of bacteria are resistant to fluoroquinolones?
A
Obligate anaerobes
16
Q
Are fluoroquinolones effective against Pseudomonas?
A
Yes!
but only some drugs
17
Q
Are fluoroquinolones effective against Mycobacteria?
A
Yes!
if it is rapidly growing
18
Q
What is special about the the drug category fluoroquinolones?
A
They are the most advanced drugs we have today
19
Q
How likely is it that bacteria will become resistant to fluoroquinolones?
A
Very likely!
20
Q
What bacterial resistance mechanism leads to a LARGE increase in the MIC value for fluoroquinolones?
A
Mutations in the drug binding sites
21
Q
What bacterial resistance mechanism leads to a SMALLER increase in the MIC value for fluoroquinolones?
A
Increased expression of drug efflux transporters
& decreased drug uptake
22
Q
What is an amphoteric substance?
A
It has both an acidic group and a basic amine group
fluoroquinolones are amphoteric
23
Q
What species have good oral bioavailability and which one have poor?
A
Good = monogastrics Poor = ruminants
24
Q
What is the only fluoroquinolone that has poor bioavailability in monogastrics?
A
Ciprofloxacin
25
How well do fluoroquinolones penetrate restricted sites?
Well!
| BBB, prostate, bone
26
What cell type accumulates fluoroquinolone drug?
Phagocytes
27
Do fluoroquinolones have a short or long half-life?
Long
28
How quickly can fluoroquinolones kill bacteria at the Cmax?
20 minutes!
29
Do fluoroquinolones produce at post-antibiotic effect? If so how for how long?
Yes
| 4-8 hrs after elimination
30
When would you reach for a fluoroquinolone antibiotic?
As a second or third drug after others have failed
31
Are fluoroquinolones effective against intracellular pathogens?
Yes!
32
What fluoroquinolone drug is approved for use in cattle? What disease is it used to treat?
Enrofloxacin (& Danofloxacin)
Bovine respiratory disease (BRD)
(only in beef cattle)
33
What fluoroquinolone drug is approved for use in swine? What disease is it used to treat?
Enrofloxacin
| Swine respiratory disease (SRD)
34
What are some of the major adverse effects of fluoroquinolones?
1. GI effects
2. Canine toxic shock syndrome
3. Arthropathy
4. Potentiates seizures
5. Retinal degeneration in cats
35
What happens in Canine toxic shock syndrome?
Associate with Enrofloxacin monotherapy
| Superantigen from killed Streptococci
36
Why can fluoroquinolones cause blindness in cats?
Genetic polymorphisms in a drug efflux pump
Drug accumulates in retina and generates free radicals
High doses of enrofloxacin
37
What are two "Nitro-" antibacterial drugs?
1. Metronidazole
| 2. Nitrofurantoin
38
Are "Nitro-" antibacterial drugs -cidal or static? What is the mechanism?
-cidal
| Nitrogens --> free radicals --> breaks DNA or RNA
39
What bacteria are susceptible to "Nitro-" antibacterial drugs?
Anaerobic bacteria!
40
What other organisms are susceptible to "Nitro-" antibacterial drugs?
Anaerobic protozoa
1. Coccidia
2. Trypanosomes
41
What is a Nitroimidazole prototype drug?
Metronidazole
42
What are some ADME characteristics about Metronidazole?
1. Lipophilic
2. Good oral bioavailability in monogastrics
3. Less oral bioavailability in ruminants
5. Great tissue penetration to restricted sites
43
What is Metronidazole's spectrum of activity?
Narrow
Bactericidal
Anaerobes only
Spirochetes & Protozoa
44
What drug is Metronidazole frequently combine with to kill Gram negative aerobes?
Aminoglycoside
45
What are some indications for using Metronidazole in dogs & cats?
1. GI = empirical treatment of diarrhea
2. GU
3. Respiratory
4. Brain abscesses
5. protozoal infection
46
Why is Metronidazole NOT approved for use in food animals?
Potential carcinogen!
47
What are some adverse effects of Metronidazole?
Not many
Mild GI disturbances
Hypersalivation in cats
Neurotoxic at high doses
48
What is the mechanism of action of Rifamycins?
Inhibit RNA synthesis
49
Are Rifamycins time-dependant or concentration dependent?
Time-dependant
50
If the effect of Rifamycins -cidal or -static?
-cidal
51
What is the risk associated with using Rifampin alone?
High risk of developing bacterial resistance
| commonly use in combinations
52
Which monogastric has surprisingly poor oral bioavailability?
Horses
53
What important to remember about Rifampin's metabolism?
Potent CYP inducer
| Increase its elimination and that of other drugs
54
What is a shocking but normal side effect of Rifampin?
Orange-red color to urine, feces & saliva!
55
What is Rifampin's spectrum of activity?
Narrow
Good against Gram positive bacteria
(not many Gram negatives!)
56
How can Rifampin's risk of bacterial resistance be reduced?
Use in combination with bacteriostatic drugs like tetracyclines or macrolides
57
What are some clinical indication for using Rifampin in horses?
Rhodococcus infections in foals
58
What are some clinical indication for using Rifampin in small animals?
Staphylococcal infections
| esp. MRSA
59
What are some clinical indication for using Rifampin in food animals?
Illegal!
60
What is main adverse effect with Rifampin?
Hepatotoxicity
61
What are the three important aminoglycosides in vet medicine?
1. Amikacin
2. Gentamicin
3. Neomycin
62
What is the method of action for aminoglycosides?
Bind to 30S bacterial ribosome
| Abnormal proteins are made
63
Are aminoglycosides -cidal or -static?
-cidal
64
Are aminoglycosides time-dependant or concentration-dependant?
Concentration-dependant
| one large dose binds many ribosomes
65
Do aminoglycosides have a post-antibiotic effect?
Yes!
66
What is the solubility and transport chemistry of aminoglycosides?
Water soluble! (sugar molecules)
Basic drugs
Energy-dependant transport into bacteria
67
What spectrum of activity do aminoglycosides have?
Narrow spectrum
68
What type of bacteria are most susceptible to aminoglycosides?
Gram negative aerobic bacilli
69
What are some special bacteria that are susceptible to aminoglycosides?
1. Pseudomonas
| 2. Proteus
70
Do aminoglycosides work on anaerobes?
No!
| drug uptake is oxygen dependant
71
What is the most important drug resistance mechanism in bacteria?
Bioinactivation of the drug
| 11 plasmid enzymes can do this
72
What is the best route of administration of aminoglycoside drugs?
SC or IM
| poor oral bioavailability
73
Why should you not mix aminoglycosides and penicillins?
Aminoglycosides are bases
Penicillins are acids
Cannot mix acidic and basic drugs together!
74
What are two newer aminoglycosides? Why do they need to be given slowly?
1. Amikacin & Gentamicin
| 2. They can paralyze the patient (NMJ blockade)
75
How well do aminoglycosides penetrate tissues?
Not very well
| but they can cross placental membranes
76
What biological fluid inactivates aminoglycosides?
Purulent debris
| wounds need to be cleaned out
77
How are aminoglycosides eliminated? What adverse effect is related to the drug's excretion?
Glomerular filtration
Excretion in urine
Risk for nephrotoxicity
78
In dogs & cats what infections are treated with amikacin or gentamicin?
1. Bacteremia
2. Skin & soft tissue
3. Bone & joints
4. Respiratory
5. Genitourinary
79
What infections are treated with aminoglycosides in horses?
1. Bacterial enteritis = neomycin
2. Uterine infections = gentamicin
3. General infections = amikacin
80
Why are aminoglycosides not commonly used in food animals?
LONG withdrawal time
| months
81
What aminoglycoside is used to treat bacterial enteritis in food animals?
Neomycin
82
Which aminoglycoside can be used to treat Swine dysentery?
Gentamicin
83
What are the three important adverse effects of aminoglycosides?
1. Nephrotoxicity = acute tubular necrosis
2. Neuromuscular block = blocks Ca++
3. Ototoxic effects = high frequency hearing loss
84
What organ can be damaged by aminoglycosides? In what direction does it progress?
Organ of Corti
| Basal (high greq) to apical (low freq)
85
What do you think of first when you hear tetracycline?
Ticks!
| arthropod infections
86
What ribosomal subunit are tetracyclines' site of action?
30S
87
What ribosomal subunit are amphenicols' site of action?
50S
88
What is the mechanism of action of tetracyclines?
Reversibly bind to 30S ribosome
| Block tRNAs from binding to the aceptor site
89
Is tetracycline -cidal or -static? Time- or concentration-dependant?
-static
| Time-dependant
90
Why is tetracycline selective for bacteria?
Taken in by bacterial active transport
91
What are two tetracycline derived drugs?
1. Chlortetracycline
| 2. Doxycycline
92
Which tetracycline derivative is shorter acting and water soluble?
Chlortetracycline
93
Which tetracycline derivative is long acting and lipid soluble?
Doxycycline
94
What are tetracyclines spectrum of activity?
Intermediate to broad spectrum
95
Which tetracycline derivative has some bactericidal activity against a few bacteria?
Doxycycline
| Time -dependant
96
What organisms are susceptible to tetracycline?
1. Gram negative & positive
2. Aerobic & anaerobic
3. Atypicals = think ticks!
4. Protozoans
97
What bacteria are usually resistant to tetracyclines?
1. Pseudomonas
| 2. Proteus
98
What type of bacteria carries the most resistance to tetracyclines? The least resistance?
Most resistant = enteric bacteria
| Least resistance = Intracellular bacteria
99
What is the most important resistance mechanism that affects tetracyclines?
Efflux pumps
| Decreased penetration of the drug
100
Why is the use of tetracyclines of public health concern?
Extensively used in food animals
Many animals harbor resistant enteric bacteria
Esp. Salmonella
101
What type of food limits tetracycline absorption?
Foods high in calcium
| Esp. milk
102
Why is oral administration of tetracyclines not a good idea in horses or ruminants?
Risk for colitis
103
What is unique about tetracycline's ADME?
Can complex with Ca and be deposited in growing teeth and bones
104
Why do tetracyclines tend to persist in the body?
Enterohepatic recycling
| Little to no metabolism
105
What is the primary route of elimination of tetracyclines?
Excreted unchanged
| Urine & bile
106
What is important to know about Doxycycline's elimination?
Excretion in the feces
| Can be used in patients with renal dysfunction
107
What infections can tetracyclines treat in cats & dogs?
Common infections
Tick borne infections
Lyme disease (off label)
108
What infections can tetracyclines treat in horses?
Potomac horse fever = neorickettsia
| Oxytetracycline
109
Which tetracycline is used most often in food animals?
Chlortetracycline
| short-acting
110
What type of infections are tetracyclines used to treat in birds?
Common bacterial infections
| Protozoan infections
111
What are the four main adverse effects of tetracyclines?
1. GI upset (esp. colitis in horses)
2. Nephrotoxicity (excreted unchanged)
3. Hepatotoxicity
4. Azotemia
112
What are the two main drugs in the group Amphenicols?
1. Chloramphenicol
| 2. Florfenicol
113
Where do Amphenicols have their site of action?
```
50S ribosome
(same action as tetracyclines but on the other subunit = 30S)
```
114
Are Amphenicols -cidal or -static?
-static
115
What type of drug can block the action of Amphenicols?
Macrolides
Lincosamides
Type B Streptogramin
= MLS antibacterial drugs
116
Which Amphenicol is banned from use in food animals and why?
Chloramphenicol causes aplastic anemia in 1/25,000 humans
117
Which of the two main Amphenicols is more potent?
Florfenicol
118
What are two bacteria that are resistant to Amphenicols?
1. Nocardia
| 2. Mycobacteria
119
How do resistent types of bacteria evade Chloramphenicol?
Acetylation of a hydroxyl group
120
What is the oral bioavailability of Amphenicols in monogastrics and ruminants?
```
Monogastrics = good
Ruminants = poor (inactivation)
```
121
How good is the tissue penetration of Amphenicols?
Very good!
Reaches protected sites
(eye & CSF)
122
What is the main mechanism of metabolism of Amphenicols?
Glucuronidation
123
How are Amphenicols excreted?
Mostly renal
| Some biliary
124
What is Chloramphenicol typically used for in companion animals?
Empirical treatment of serious ANAEROBIC infection
125
Can Florfenicol be used in food animals? If so for what infections?
Yes
| Respiratory infections
126
What are three main adverse effects of Amphenicols?
1. Bone marrow suppression
2. GI upset
3. Hypotension
(calves given drug IV)
127
What three drugs are included in MLS antibacterial drugs?
1. Macrolides
2. Lincosamides
3. Streptogramins
128
What drug can be blocked from its binding site by MLS drugs?
Chloramphenicol
129
What is the main mechanism of action of Macrolide drugs?
Interrupt protein synthesis
1. Prematurely detach growing peptide chain
2. Obstruct the exit of the peptide chain
130
What is the main mechanism of action of Lincosamide drugs?
Interrupt protein synthesis
| 1. Inhibits tRNA transfer of AAs
131
What is the main mechanism of action of Streptogramin drugs?
Interrupt protein synthesis
| Uses both Macrolides and Lincosamides mechanisms
132
Are Macrolides and Lincosamides acids or bases?
Bases
133
Macrolides and Lincosamides penetrate tissue well except which tissue?
CNS
134
Macrolides and Lincosamides have what spectrum of activity?
Narrow
135
What bacteria are usually not susceptible to Macrolides and Lincosamides?
Aerobic Gram negative bacteria
136
What bacteria are typically susceptible to Macrolides and Lincosamides?
Gram positive bacteria
Mycoplasma
Some Gram negative anaerobes
137
Are Macrolides and Lincosamides concentration- or time-dependant? -cidal or -static?
Time-dependant
| Bacteriostatic
138
What are some adverse effects of Macrolides and Lincosamides?
1. Diarrhea
| 2. Enteric super infections esp. horses
139
How are resistance genes transferred between bacteria for Macrolides and Lincosamides drugs?
Horizontal transfer!
| Via mobile elements
140
How to target modifications by bacteria affect resistance in the other MLS drug categories?
They are cross-resistant!
141
Name three important Macrolides.
1. Erythromycin
2. Tylosin
3. Tilmicosin
142
Name three important Lincosamides.
1. Lincomycin
2. Clindamycin
3. Pirlimycin
143
Name one important Streptogramin drug?
Virginiamycin
144
Name one important Pleuromutilin drug?
Tiamulin
145
Which Macrolide is destroyed by gastric acid?
Erythromycin
146
What is important to know about the distribution of Macrolides in the body?
Drug concentration is higher in the tissues than in the body
147
What is the major route of elimination of Macrolides?
Bile
| some in the urine
148
Which Lincosamide has the best oral bioavailability?
Clindamycin
149
What bacteria is NOT susceptible to Macrolides and Lincosamides?
Gram negative bacteria
150
What are Macrolides and Lincosamides used as a second choice in patients sensitive to the first choice drug?
Penicillin
151
Which two MLS drugs are mostly used in companion animal medicine?
1. Erythromycin
| 2. Clindamycin
152
Which two MLS drugs are mostly used in food animal medicine?
1. Tilmicosin
| 2. Lincomycin
153
What MLS drug is used in many species?
Tylosin
154
What MLS drug is used to treat Campylobacter enteritis in dogs and R. equi infections in foals?
Erythromycin
155
What drug can be used as an alternative to Erythromycin and has greater activity against Gram negative bacteria?
Azithromycin
156
What drug is effective for treating chronic colitis and acute lung infections in dogs & cats?
Tylosin
157
What drug is good for treating recurrent skin Staphlococcal infections and other infections?
Clindamycin
158
What drug is good for mastitis in ruminants and proliferative enteropathy in swine?
Erythromycin
159
What drug is effective against mycoplasma infections?
Tylosin
160
What drug is approved for use only in swine?
Linomycin
161
In which species are MLS antibiotics contraindicated? Why?
1. Pocket pets
2. Rabbits
3. Horses
= causes GI superinfections
162
What is a side effect of Macrolides?
Diarrhea
| macrolides are motilides!
163
What drug causes lip-smacking and salivation in cats?
Clindamycin
164
What adverse reaction can occur with high doses of Tilmicosin given i.v.?
Cardiotoxicosis
165
What is the main use of Streptogramins?
Livestock growth promoter
166
What is another drug used as a growth promoter?
Macrolide Tylosin
167
What is the oral bioavailability of Streptogramins?
Poor
| confines drug to GI tract
168
What is a specific Streptogramin drug?
Virginiamycin
169
What is the Pleuromutilin drug Tiamulin commonly used for?
Treatment of infections in swine
170
How many layers of Peptidoglycan are in Gram negative bacteria? Gram positive bacteria?
Gram negative = one layer
| Gram positive = many layers < 40
171
How to B-Lactams act against the bacteria's cell wall?
1. Penetration of bacterial cell wall
2. Binding to penicillin-binding proteins
3. Interruption of peptidoglycan cross-linkage
4. Arrest in cell wall formation
5. Cell lysis!
172
What protein does the B-Lactam ring structure inhibit?
Bacterial transpeptidases
| = penicillin binding proteins (PBPs)
173
Are B-Lactam drugs time- or concentration-dependant? -cidal or -static?
Time-dependant
| Bactericidal
174
What role do Autolysins have a cell wall breakdown?
B-Lactams inhibit cell wall synthesis allowing autolysins to degrade cell wall membrane unchecked
175
Can B-lactam drugs reach intracellular bacteria?
No
176
Which bacteria are most susceptible to B-lactam drugs?
Gram positive
177
What are three main mechanisms of bacterial resistance to B-lactam drugs?
1. Restrict drug access (Gram negative)
2. Change PBP target molecule
3. Produce B-lactamases that breakdown the drug's ring
178
What type of B-lactamase enzyme expression is clinically important?
Plasmid-associated B-lactamases
179
How does the location of the B-lactamase differ between gram negative and gram positive bacteria?
Gram negative = periplasmic space
| Gram positive = extracellular space
180
Which groups of B-lactamases are insensitive to clavulanic acid?
Group 1 & 3
181
Which drug is still able to escape B-lactamase activity?
Carbapenems
| newest drugs
182
What is a gram positive bacteria that produces B-lactamases?
Staphlococcus
183
What types of Gram negative bacteria produce B-lactamases?
Enterobacteriaceae
| E. coli, pseudomonas, proteus, salmonella, etc
184
What are two B-lactamase inhibitors?
1. Clavulanic acid
| 2. Tazobactum
185
What animals should not receive Clavulanic acid?
Pocket pets!
| Use caution in herbivores and horses
186
How do B-lactamase inhibitors affect the MIC value?
Reduce the MIC value
187
What are 4 important categories of B-lactam drugs?
1. Penicillin = wide
2. Cephalosporin = narrow-wide
3. Carbapenems = wide
4. Monobactams = narrow
188
What is the spectrum of activity of Penicillin G?
Narrow
| Mostly Gram negative bacteria
189
What is the spectrum of activity of cloxacillin?
Narrow
| But works against MSSA (staphylococci)
190
What is the spectrum of activity of Ampicillin, Amoxicillin, Piperacillin, Ticarcillin?
Broadest
| Even works against Pseudomonas, Proteus, Klebsiella
191
Which generation of cephalosporins are better against gram negative bacteria?
Newer generations
| 4th & 5th
192
What is a first generation cephalosporin?
Cephalexin
| mostly Gram positive
193
What is a third generation cephalosporin?
Ceftiofur
Cefovecin
Cefpodoxime
(more Gram negatives and pseudomonas)
194
What is the spectrum of activity of Carbapenems?
Broadest of all B-Lactam drugs
| Least sensitivity to B-Lactamases
195
Are penicillins acids or bases?
Acids
196
How are penicillins stored?
As dry powder
197
What is the distribution of penicillins?
Low Vd!
| Poor penetration
198
How are penicillins secreted?
90% in the urine
199
Are cephalosporins acids or bases?
Also acids = low oral bioavailability
200
Are carbapenems also acids?
Yes!
| Also Low Vd, short T1/2, excretion in the urine
201
Which B-Lactam is best for urinary tract infections?
Carbapenems
| active in urine
202
How do cephalosporins relate to penicillins in effectiveness?
Cephalosporins are one step ahead of penicillins
203
Which drug is used to treat serious pseudomonas infections in small animals?
3rd generation cephalosporins
204
Why should B-lactam drugs not be used at high doses even though the dose is safe for the patient?
High doses can produce bacteriostatic effects
| Limiting bactericidal effects
205
What drugs should only be considered after first-line drugs have failed in small animal patients?
Carbapenems
206
What are some adverse effects of B-lactam drugs?
1. Hypersensitivity reactions
2. Disruption of commensal flora
3. Nephrotoxicity
4. Blood dyscrasias
