Exam 4 Flashcards
1
Q
What four characteristics are antimicrobial drugs classified by
A
1) Class of microorganism to which they show activity
2) Antibacterial spectrum of activity
3) Bacteriostatic or bactericidal
4) Time or Concentration-dependent activity
2
Q
Broad spectrum antimicrobials
A
active against a wide range of bacteria and potentially active against mycoplasma, rickettsia, chlamydia, protozoa
3
Q
Narrow spectrum antimicrobials
A
antimicrobials that only inhibit bacteria
4
Q
Narrow spectrum antibacterials
A
may only inhibit gram positive or gram negative bacteria
5
Q
Broad spectrum antibacterials
A
inhibit both gram positive and gram negative and potentially aerobic and anaerobic bacteria
6
Q
All antimicrobials are _________ at low concentrations and stop organisms from multiplying but do not call
A
Bacteriostatic
7
Q
What are some classes of antimicrobials that are bacteriostatic at all concentrations
A
tetracyclines and sulfonamide
8
Q
Some antimicrobials are capable of being _______ if high enough concentration
A
Bactericidal. almost always dependent upon target bacteria multiplying at time of the drug exposure
9
Q
Minimum inhibitory concentration (MIC)
A
the lowest concentration of a drug required to inhibit visible growth of bacteria in a test tube
-Determined using a dilution test
10
Q
Minimum bactericidal concentration
A
the minimum concentration of a drug required to inhibit visible growth of bacteria in a test tube (Can be 2-4x or more the MIC value)
11
Q
What is the breakpoint MIC
A
the value above which plasma concentrations are unlikely to be achieved and thus clinical benefit is unlikely with labeled dosing
12
Q
What is the relationship between MIC and breakpoint values
A
how the minimum inhibitory concentration is used to determine if a particular infection is likely to be clinically sensitive, intermediate, or resistant
13
Q
How do you select an antimicrobial agent based on MIC and breakpoint values
A
you want the agent MIC to be sensitive (S) , and be able to move 2 clicks and still be sensitive
14
Q
Post-Antibiotic effect
A
the persistent inhibition of bacterial growth by an antimicrobial agent even when drug levels become below its MIC
-delayed re-growth of surviving bacteria
15
Q
How would you measure concentration dependent activity of an antimicrobial
A
The concentration peak (Cmax) of the serum
ex: aminoglycosides
16
Q
How would you measure both concentration and time dependent activity of an antimicrobial?
A
The area under the curve (AUC)
ex: fluoroquinolones
17
Q
What is an example of an antimicrobial that is time dependent
A
beta lactams
18
Q
What is an example of an antimicrobial that is concentration and time (AUC) dependent?
A
fluoroquinolones
19
Q
What is an example of an antimicrobial that is concentration dependent
A
aminoglycosides
20
Q
How might you minimize the Cmax of a drug?
A
give a lower dose more frequently
21
Q
How might you achieve T>MIC
A
lower dose more frequently to acheieve a lenght of time where serum concentrations exceed the minimum inhibitory concentration (MIC)
ex: Beta lactams, some macrolides, tetracyclines, TMS, chloramphenicol
22
Q
What does time dependent activities mean
A
the length of time spent above the MIC matters, increasing the concentration several fold above the MIC does not significantly increase microbial killing
think: betalactams, some macrolides, tetracyclines, TMS, chloramphenicol
23
Q
What does concentration dependent activities mean
A
the maximum serum concentration achieved is the most significant factor determining the efficacy of some drugs such as Aminiglycosides, metronidazole, +/- fluoroquinolones
*Rate of killing increases as drug concentration increases further above MIC, not necessarily or even beneficial to maintain drug levels above MIC between doses
24
Q
How can you optimize Cmax/MIC
A
give a higher dose less frequently
25
What does both time and concentration dependent activities mean?
some drugs exert characteristics where best predictor of efficacy is the 24hours area under the serum concentration versus time curve to MIC ratio (AUC/MIC)
ex: gylcopeptides, rifampin, and to some extent the fluoroquinolone
26
What dosing schedule is most likely to be used with both time and concentration based activities
once a day (qD) or twice a day
as long as AUC/MIC is reached in both regiments
27
What dosing is best for time dependent?
lower dose more frequently
28
Why might you combine antimicrobial drugs together
1) Antimicrobial synergism
2) Polymicrobial infection
3) Decrease emergence of resistant isolates
4) Decrease dose-related toxicity
29
Additive/Indifferent interaction
the activity in combination equals the sum of separate independent activities
may not be economically justifiale
30
Synergistic effect
activity of the combined antimicrobial agents is significantly greater than the sum of the independent activites
31
Antagonistic effect
activity of the combination is significantly less than the sum of the independent activities
32
Reasons you might choose an antibiotic
1) Identify organism at site of infection
2) Knowledge of usual susceptibility profile
3) Knowledge of factors that affect drug concentration at the site of infection
4) Knowledge of drug toxicity and factors that enhance it
5) Cost of treatment
6) Knowledge of regulations about the use of a drug including withdrawal times when appropriate
33
Ciprofloxacin is a ___________
fluoroquinolone
34
Enrofloxacin is a__________
fluoroquinolone
35
Marblofloxacin is a _________
fluoroquinolone
36
Pradofloxacin is a ________
fluoroquinolone
37
What is the mechanism of fluoroquinolones?
-inhibition of bacterial DNA gyrase and/or topoisomerase IV leading to the inhibition of DNA supercoiling and replication
-Enter the cell via porins and accumulate rapidly inside susceptible bacteria
-Concentration dependent (Cmax:MIC or AUC:MIC)
-Post-antibioitc effect in enrofloxacin and orbifloxacin
38
All fluoroquinolones discussed end with:
-floxacin
39
Fluoroquinolones are best absorbed via:
oral route
-decreased absorpotion if high concentrations of divalent/trivalent cations (ex: antacids, nursing young)
-poor absorption orally in ADULT ruminants
40
What can decrease the absorption of fluoroquinolones?
if high concentrations of divalent/trivalent cations (ex: antacids, nursing young)
41
What fluoroquinolone is best absorbed in horses?
Enrofloxacin, Ciprofloxacin is poorly absorbed
42
Fluoroquinolone distribution
achieve concentrations at tissues as high as plasma
*reaches therapeutic doses from gram - organisms in the CNS and eye
* Rapidly accumulate in macrophages and neutrophils may lead to higher concentrations in infected tissues compared to healthy
-Urinary and prostate accumulation
43
In many species, Enrofloxacin is metabolized to form
ciprofloxacin via de-ethylation
(up to 40% in the dog)
44
Generations of quinolone drugs
1st: older drugs (nalidixic acid, flumequine) - activity restricted to enterobacteriaceae
2nd: all but one vet quinolone, extended spectrum of activity but limited against Streptococci and obligate anaerobes
3rd: Pradofloxacin
Improved in-vitro activity agaisnt Streptococci and obligate anaerboes
45
What is the only vet med quinolone to be 3rd generational?
Pradofloxacin, imporved activity against Streptococci and obligate anaerobe
46
2nd generational quinolones have an extended spectrum of activity but are limited against:
Streptococci and obligate anaerobes
47
Why can therapeutic concentration of ciprofloxacin be reached with dosing calculated to achieve effective enrofloxacin concentrations
Because MICs for ciprofloxacin are often lower lower than those for enrofloxacin
48
Fluroquinolones have activity against:
Good:
Gram - aerobes including enterobacteriaceae (E coli, Klebsiella, Proteus, Salmonella, Actinobacillus, Brucella, Leptospura, Pasteurella), Mycoplasma, Rickettsia
Moderate/Variable Activity:
Gram + aerobes: Streptococci (agalactiae, suis, zooepidemicus) Rhodococcus, mycobacteria
49
Anaerobic Bacteria are normally resistant against all fluoroquinolones except?
Pradofloxacin
50
Generally, all fluoroquinolones (except Pradofloxacin) are better is aerobes or anaerobes?
aerobes (gram - more than +)
51
T/F Fluoroquinolones have mycoplasma spp. activity
True
52
What is a consequence of enrofloxacin in cats when doses are higher than 5mg/kg/day
-Retinal degeneration due to reduced function of ABCG2/BCRP efflux transporter in cat retina leading to drug accumulation and photoreaction
Also neurotoxic effects have been reported
53
What is a result of fluoroquinolone admin. during immature animals
-Arthropathies and cartilage erosion in weight bearing joints (immature cats, dogs, and horses)
Avoid use in small and medium dogs during rapid growth
54
What fluoroquinolone has a greater BBB penetration and more likely to cause neurotoxic effects through GABA receptor inhibition
Enrofloxacin
55
How can enrofloxacin cause neurotoxic effects
through GABA receptor inhibiton
56
What can be a result of most antimicrobial agents in horeses
enterocolitis
57
What drugs have antagonism effects with ciprofloxin/enrofloxin?
chloramphenicol and rifampin
58
What are the four main categories of resistance to fluoroquinolones
1) Target modification
2) Decreased permeability
3) Efflux
4) Target protection
59
Target modification resistance to fluoroquinolones
Stepwise Mutation in DNA gyrase (gyrA mutation) with secondary mutations of Topo IV (parC mutation)
60
Why does Campylobacter have a higher resistance to fluoroquinolones
because it does not have Topoisomerase IV and thus a single mutation can lead to high level of resistance because it only needs a mutation in DNA gyrase
why fluoroquinolones are banned in poultry production
61
Why are fluoroquinolones banned in poultry production
because they do not have Topo IV so only a single mutation in DNA gyrase is needed for resistance
62
What factors lead to fluoroquinolone resistance through reduced intracellular drug levels
1) Altered outer membrane porins- decrease permeability of cell wall to drug
2) Induced membrane efflux pumps- removing the drug before they can interact with DNA gyrase and Topo IV
63
How does target protection resistance to fluoroquinolones occur?
quinolone resistance gene qnr functioning to protect DNA gyrase (not Topo IV) from inhibition by fluoroquinolones
result in small decrease in drug susceptibility
64
How does the qnr gene protect bacteria from quinolones
it protects DNA gyrase, not Topo IV
65
How do you reduce emergence of resistance to fluoroquinolones
targeting the dosage to the MIC of the pathogen to the clinical resolution of infection
66
Pharmacokinetic properties of quinolones
good oral absorption
large volume of distribution
good intracellular drug penetration
extended elimination half lives allow for every 24-48 hour
67
How were beta lactams discovered?
in 1928 when Penicilium mold lysed colonies of staph
1940: isolated into powder
1945: Cephalosporing C from Cephalsosporium acremonium
68
What improves the pharmacokinetic properties of beta-lactam?
substitiutions on the beta-lactam ring increases resistance to beta-lactamase enzymes, enhances activity and improves properties
69
Penicillin G is a _________
natural penicillin (beta-lactam)
70
Ampicillin is a _______
amino penicillin (beta-lactam)
71
Amoxicillin is a ________
amino penicillin (beta-lactam)
72
Oxacillin is a _______
anti-staphylococcal penicillin (beta-lactam)
73
Piperacillin is a __________
extended spectrum penicillin
74
What is the mechanism of action of penicillins?
prevention of cell wall formation and cause lysis of bacterial cells to produce a bactericidal action
-slower kill rates than fluoroquinolones
inhibition of peptidoglycan synthesis through interfering with penicillin-binding proteins (peptidoglycan active enzymes)
Bactericidal only for growing cells (those undergoing active cell wall synthesis
*4 member ring of beta lactam mimics D-Ala peptide terminus that serves as a natural substrate for transpeptidase activity during cell wall synthesis, blocks covalent bonds and weakens wall leading to lysis due to high internal osmotic pressure
75
4 ways beta-lactams differ in their gram + vs - activity
1) Differences in receptor sites on PBPs
2) Relative amount of peptidoglycan present
3) Ability to penetrate outer cell membrane of gram -
4) Resistance to the different types of beta-lactamase enzymes present
76
Are beta-lactams time or concentration dependent
TIME DEPENDENT- the length of time that antibiotic concentrations at the site of infection exceed the MIC (T
77
What is the eagle effect with beta-lactams?
When concentrations are above the optimal killing concentration, result in reduced bactericidal effect due to binding to PBPs that cause growth arrest; the failure to grow results in failure to be killed by antibiotic
*tendency to overdose with these drugs due to large safety margin
78
What is the primary mechanism of resistance to beta-lactams?
the production of beta-lactamase enzymes (Serine and Metallo beta-lactamases
these break the beta-lactam ring destroying the pharmacore
extracellularly produced (gram +)
periplasmic produced (gram -)
79
Beta-Lactamase Enzyme Inhibitors
block resistance to beta-lactams via beta-lactamase enzymes to inhibit them
-Avibactam
-Clavulanic acid
-Tazobactam
80
Clavulanic acid is a ______
Beta-lactamase enzyme inhibitor
81
Avibactam is a ________
Beta-lactamase enzyme inhibitor
82
Tazobactam is a ______
Beta-lactamase enzyme inhibitor
83
Why are penicillins poorly absorbed orally
because they are acid labile
84
Why do you need to frequently dose penicillins
because of short half life/rapid elimination and time dependent activity
do not cross biologic membranes easily
85
What effect does impaired renal function have on elimination of penicillins
it is eliminated almost entirely through renal excretion but you do need to adjust dosage because of wide safety margin
86
Penicillin G
a natural penicillin
mostly active against gram + aerobes and anaerobes (less against Staphylococcus, Gram - and enterobacteriacea are generally resistant)
87
What can occur with Penicillin G toxicity
rare but often hypersensitivity reaction, can cayse anaphylaxis in sensitive individuals - potassium
88
What form of Natural/benzyl penicillins can be orally absorbed
Penicillin V- it resists acid hydrolysis and is administered orally
same spectrum as other benzyl penicillins
89
Procaine penicillin
slowly absorbing penicillins
DO NOT USE ON BIRDS, SNAKES, TURTLES, GUINEA PIGS, OR CHINCHILLAS
90
What species should you you not use procaine formulations on?
-Birds
-Snakes
-Turtles
-Guinea pigs
-Chinchillas
91
What is the spectrum of activity of ampicillin and amoxicillin
Increased to include many gram - aerobes (E Coli, Proteus, Pasteurella)
Slightly less activity than Pen G against Gram + an anaerobes
Acid stable with amoxicillin having a greater bioavailability than ampicillin
92
What beta-lactams are resistant to beta-lactamases produced by Staph aureus and used in the treatment of bovine staphylococcal mastitis
-Cloxacillin, Dicloxacillin, Oxacillin, Methicillin
93
What penicillin is used to test methicillin sensitivity in vitro
oxacillin
94
MRSA/MRSP
methicillin resistant staphylococcus that is resistant to all beta-lactams due to mecA gene producing an alternative PBP (PBP2A)
95
All other penicillins do not have activity against Pseudomonas except...
Carbenicillin, Ticarcillin, and Piperacillin (Antipseudomonal/Extended Spectrum Pencillins)
96
What can be used for treatment of otitis externa in dogs caused by Pseudomonas aeruginosa
Ticarcillin
97
Why should you not give Ampicillin to small rodents and rabbits
potential for disturbing normal intestinal flora
and can produce Clostridial colitis
98
What is the best penicillin for the treatment of urinary tract infections
Amoxicillin
99
What is the drug of choice for treating leptospirosis
Amoxicillin (because it is a gram negative aerobe)
100
What are the drugs of choice for mixed aerobic/anaerobic infections such as cat-bite infections
Ampicillin or amoxicillin
101
T/F Cephalosporins are more susceptible to beta-lactamase enzymes than beta-lactams
F
102
What route do cephalosporins typically require?
Parenteral, short-half life-require frequent dosing
poor intracellular penetration
103
Are cephalosporins time dependent or concentration dependent?
Time dependent
104
Are cephalosporins bacteriostatic or bacteriocidal?
Bactericidal
105
In general as you increase the cephalosporing generation: coverage increase from-
gram + coverage to gram - coverage (but at the cost of gram + coverage)
106
How does cephalosporin resistance occur?
Same as pencillins
1) PBP modification
2) Reduced permeability and increase efflux
3) Beta-lactamase production (important)
107
1st generation cephalosporins activity
Good activity: Gram + aerobes, including lactamase prodicing staphylococcus and streptococcus
Moderate: Gram - enterobacteriacea
No activity against Pseudomonas or Enterobacter
108
Cefazolin, Cephapirin, Cephalothin (Injectable)
Cephalexin and Cefadroxil (oral)
1st generation cephalosporins
109
Why might you use 1st generation cephalosporins?
skin and urinary tract infections and other non-specific infections caused by staphylococci and streptococci (good gram + aerobe activity), enterobacteriacea and some anaerobes
110
How do the different Cephalosporins differ in their route of admin
1st gen: Oral or injectable
2nd gen:Parenteral (no oral)
3rd gen: injectable
111
How do 2nd generation Cephalosporins differ from 1st gen?
they have slightly more gram - and anaerobe coverage with slightly less gram + coverage than 1st gen
112
Cephamycins
2nd generational cephalosporins that are derived from Streptomyces rather than Cephalosporium (Cefotetan and Cefoxitin) and very stable to beta-lactamases
113
Cefoxitin
a 2nd generation cephalosporin
(derived from Streptomyces)
treat severe mixed infections with anaerobes such as aspiration pneumonia, bite infections, peritonitis, and prophylaxis in colonic surgery or ruptured intestine
114
What category is Cefoxitin?
a 2nd generational cephalosporin
(derived from Streptomyces)
115
What is the Cephalosporin with best activity against Pseudomonas
Ceftazidime
116
Ceftazidime
a 3rd generation cephalosporin (extended spectrum of activity against gram - and some anaerobes)
*good activity against pseudomonas
117
Ceftiofur
a 3rd generational cephalosporin used for respiratory disease of cattle, sheep, swine, and horses
urinary tract infections in dogs
(naxcel) is a slow releasing injectable form
118
Cefovecin
a 3rd generational cephalosporin named Convenia
SQ injection for cats and dogs that can used as a single treatment
high MIC for Staph pseudointermedius for 14 days
119
Cefpodoxime
Simplifcef- a 3rd generational cephalsporine
prodrug - esterified in GI tract to release active cefpodoxime
longer half life than other cephalosporins
*No Pseudomonas activity unlike other 3rd generational
120
What are the two 3rd generational Cephalosporins that do not have activity against Pseudomonas
1) Cefpodoxine
2) Cefovecin
121
What 3rd generational cephalosporins have activity against Pseudomonas and which ones dont
DO: Ceftiofur, Cefovecin (Convenia)
DONT: Cefpodoxime and Cefovecin
122
T/F 3rd and 4th generation cephalosporins are not first line drugs for uncomplicated infections
T
123
Convenia and Simplicef are often used as a first line of drugs for skin and urinary tract infections because of less frequent dosing. Why is this bad
They are 3rd generational cephalosporins
-Most cat bite infections can be successfully treated with amoxicillin (Clavamox)
-Most staphylococcal skin infections can be treated with cephalexin and a 3rd gen is not needed
124
Cephalexin
a 1st generational cephalosporing that is often used staphylococcal skin infections because of its good activity against gram + aerobes
125
Why should you be careful with 3rd and 4th generational cephalosporins
because they are extended spectrum and have the ability to induce super beta-lactamses in bacteria that render them highly resistant and thus no beta-lactams may be effective
*Big concern - banned for extralabled use in food animals
126
Carbapenems
derivatives of streptomyces spp.
Widest activity of any antibiotic, except trovafloxacin
Activity against almost all clinically important aerobic or anaerobic gram + or gram - cocci or rods
Resistant to almost all bacteria beta-lactamase enzymes
All are pareneterally
Last resort in human med
127
Imipenem
a carbapenem that is rapidly hydrolyzed by a dehydropeptidase in th renal tubules to a nephrotoxic compound
Always administered with cilastatin to inhibit dihydropeptidase and prevent nephrotoxicity
IV only
Tx of ESBL producing Enterobacteriacea when a single drug is required
128
What should you give with Imipenem to prevent nephrotoxicity by inhibiting dihydropeptidase
Cilastatin
129
Cilastatin is commonly given with _______ to prevent nephrotoxicity
Imipenem
130
Meropenem
a carbapenem that is sometimes used off label (use SQ instead IV)
Similar activity to imipenem
not a first line of drug
131
T/F Carbapenems can be used as a first line of drug
F
132
What should you combine with Carbapenems for treatment of Pseudomonas to reduce resistance potential
Aminoglycoside
133
Aztreonam
a monobactam
stable to most beta-lactamase enzumes
Almost all gram - aerobes
resistance seen in gram + and anaerobes
Potential for use as substitute for more toxic aminoglycoside for mixed infections
134
What is the potential use of Aztreonam?
sunstitute for the more toxic aminoglycoside for tx of mixed infections
-With clindamycin/Metronidazole for mixed aerobic/anaerobic infections
-With erythromycin in mixed infections where gram + organisms are present
135
What is clavulanic acid used for?
in combination with beta-lactam antibiotics to block resistance via beta-lactamase enzymes to inhibit them
136
What are the three classes of protein synthesis antimicrobials?
1) Tetracyclines
2) Chloramphenicol
3) Aminoglycosides
137
How do protein synthesis antimicrobials work?
By binding to either the 30S or 50S ribosomal subunit to inhibit the formation of polypeptide chains and block protein synthesis
138
Chloramphenicol binds to the _______
50S ribosomal subunit and inhibits the formation of peptide bond
139
Tetracyclines mechanism of action
interfere with the attachment of tRNA to mRNA ribosome complex
30S small ribosomal unit
140
Tetracycline spectrum of activity
Gram + and _ bacteria
Mycoplasma
Some mycobacteria
Most a-proteobacteria (Anaplasma, Rickettsia)
Protzoan and filarial parasites
141
What do tetracycline bind to
16S rRNA and S7 protein of the 30S ribosomal subunit
inhibits rRNA from binding to the docking site on the ribosome and mRNA codon to block peptide synthesis
also have anti-inflammatory activity- inhibit metalloproteinase enzymes, can scavenge reactive oxygen species (ROS)
142
What class is Doxycycline
a tetracycline- binds 30S subunit
143
Are tetracyclines bacteriocidal or bacteriostatic
generally bacteriostatic
144
What are the main mechanisms of Tetracycline resistance
1) Energy dependent efflux systems that exchange an extracellular H+ for a drug-Mg2+ complex
2) Ribosomal protection proteins that remove the tetracycline from binding site near the tRNA docking site
*flavin preventing cation chelation and ribosomal bind
*16S rRNA mutation
*Stress-induced down regulation of porins which drugs use to enter gram - walls
145
What is one of the few antimicrobials drugs that is osteotropic
Tetracyclines
146
What can reduce the already poor oral bioavailability or tetracyclines?
milk replacer or antiacids
147
Why do tetracyclines have longer half lifes
although it excreted primarily through glomerular filtrations it enter enterohepatic circulation
148
What antimicrobial is associated with esophageal strictures in cats?
Doxycycline tablets
149
What antimicrobial is associated with yellow discoloration of the teeth
Tetracycline
150
Tetracycline toxicity
1) Irritants- vomiting (oral), tissue damage
2) Enterocolitis = imbalance of intestinal flora
3) Esophageal stricture cats (tablets)
4) Acute heart toxicity (binding calcium)
5) Renal toxicosis with high dose
6) Yellow discoloration of teeth
151
What is the drug of choice for treating Rickettsial infections
Doxycycline
152
What is the treatment of choice for Chamidophilia felis
Doxycycline
153
What are the clinical implicatons of tetracyclines
1) Bovine/porcine respiratory disease complexes
2) Plague, tularemia, and listeriosis
3) Rickettsia
4) Chlamidophilia felis
154
What does Chloramphenicol bind to?
the 50S subunit of bacterial ribsome and inhibits peptidyl transferase to growing peptide
also inhibits mitochondrial protein synthesis in bone marrow
generally bacteriostatic
155
Chloramphenicol is bacteriocidal or bacteriostatic?
Bacteriostatic
156
Chloramphenicol isborad spectrum but what does it have poor activity against
Mycobacterium
Nocardia
resistance to gram - enterics like e coli
157
Chloramphenicol spectrum of activity
broad spectrum
good: gram positive aerobes including Actinmyces, Bacillus anthracis, MRSP NA strainsl gram - aerobes and anaerobes including Bacteriodes and Clostridium
Intermediate activity: rhodococcus equi
Poor activity: Mycobacterium spp, Nocardia, resistance often develops with gram - enterics such as E coli
158
What is the most frequent mechanism of resistance to chloramphenicol
enzymatic inactivation by acetylation of the drug by bacterial chloramphenicol acetyltransferases (CAT)- common on enterbacteriacea and Pasterurellacea
also efflux of drug from bacterial cells by either specific or multirug transporters
159
Chloramphenicol PK properties
rapidly absorbed from oral and parenteral administration
Wide distribution with effective concentrations in almost all tissues including CNS and eye
Hepatic metabolism with conjugation to glucuronic acid (glucuronidation) leads to widely variable elimination half-life across species
160
Why is Chloramphenicol activity prolonged in cats
due to limited glucuronidation capacity
161
What are the toxic effects of chloramphenicol
1) inhibitor of cytochrome p450 enzymes= interaction. fatal if with phenobarbital
2) Bone marrow suppression due to inhibition of mitochondrial protein synthesis, dose depedent bone marrow suppression
162
What is the main toxicity of chloramphenicol
bone marrow suppression
163
T/F Chloramphenicol is not okay to use in food animals
T, use florfenicol instead
164
What should be used instead of chloramphenicol in food animal settings?
Florfenicol
165
What are the clinical applications of Chloramphenicol?
*Serious ocular infections, prostatitis, otitis media/interna and salmonellosis in horses, dogs, and cats
-Treatment should NOT exceed 10 days, especially in cats
166
What is one of the few antimicrobial drugs that can be safely administered to horses by mouth?
Chloramphenicol
167
Are aminoglycosides bactericidal or bacteriostatic
bactericidal
168
What is the mechanism of action of aminoglycosides
inhibit protein synthesis by binding to the 30S ribosomal subunit (same as tetracyclines) and cause misreading of the genetic code
169
What true classes of antimicrobials bind to the 30S subunit?
Tetracyclines
Aminoglycosides
170
Florfenicol is a _______
Acetamide (same as chloramphenicol)
171
Why is combining a cell wall inhibitor with aminoglycoside synergisitic?
Because aminoglycosides need to penetrate the bacterial cell wall first
172
What group of microbes are aminoglycosides not as effective against and why?
-Anaerobes
*Bacteria need to actively pump aminoglycosides into the cell via an oxygen-dependent mechanism
173
Are aminoglycosides time or concentration dependent
Concentration dependent- target concentration needs to be at least 10x the MIC
Significant post-antibioitic effect where when concentration have dropped, bacteria are more susceptible to host defenses
174
What environment increases the activity of aminoglycosides?
alkaline environments
-alkalizing the urine will increase efficacy for UTI treatment with aminoglyosides
175
What is the spectrum of activity of aminoglycosides?
Primarily against Aerobic, gram - bacteria
some gram + are also (Staph more than Strep, strep efficacy can be increases with beta-lactam)
NOT effective against anaerobic bacteria
176
What group of antimicrobials end with -amycin/amicin
aminoglycosides or macrolides idk
177
Gentamicin is a ______
aminoglycoside
178
Amikacin is a ______
aminoglycoside
179
Tobramycin is a ______
aminoglycoside
180
What aminoglycoside is highest in potency, spectrum of activity, and stability against enzyme-mediated inactivation
*Amikacin > tobramycin > gentacin >Neomycin = kanmycin > streptomycin
181
How does aminoglycoside resistance often occur?
in form of plasmid-mediated enzymes that acetylate the aminoglycoside which prevents it from binding to the 30S ribosomal subunit
*also reduced reuptake via first exposure adaptive resistance
182
T/F aminoglycosides are best absorbed orally
F- poor oral absorption- almost all application require parenteral administration
183
All aminoglycosides cause varying degrees of __________ toxicity
Ototoxicity (vestibulocochlear)
Nephrotoxicity
184
What is the most common adverse effect of aminoglycoside therapy?
*Acute tubular necrosis
also some defree of ototoxicity and nephrotoxicity
Rapid IV admin-bradycardia and reduced blood pressure
neuromuscular blockade is rare but if given post surgery can potentiate the effects of other non-depolarizing NMJ blocking- treat with Ca-chloride or Ca-gluconate
185
Where do aminoglycosides accumulate and cause damage?
proximal tubular cells leading to acute tubular necrosis
not associated with peak concentration but duration of therapy, number of doses per day, volume depletion, acidosis, age, and elevated trough concentrations
186
What three ways might you reduce the nephrotoxicity of aminoglycosides?
1) Calcium supplementation (cations displace/prevents cationic drug from binding to anionic phsopholipid
2) Feeding high-protein diet such as alfalfa and >25% in small animals- also increases GFR and renal blood flow which reduces aminoglycoside accumulation
3) administer once-daily in higher doses, allow trough concentrations to drop below critical level before next dose
187
What should be monitored during aminoglycoside administration?
therapeutic drug monitoring to evaluate plasma concentration to ensure that trough concentrations are appropriate before the next dose.
sample 1 and 8 hr after dosing t. increases elimination half life is a very senstivie indicator of early tubular insult
Also monito using increase in urine GGT, GGT:creatinine ratio, development of proteinuria, elevations in BUN and creatinine are not seen until at least 7 days
188
Neomycin
an aminoglycoside (30S) that is toxic and largely restricted to topical or oral use for treatment of enterobacteriacea
189
Why might you use aminoglycosides?
Toxicity so limited use
-Neomycin restricted to topical or oral use
-Less toxic reserved for parenteral treatment of severe sepsis caused by gram - aerobes and the treatment of MRSP infections
190
What are macrolide mechanism of action
protein synthesis inhibitor- irreversibly bind to 50S subunit (like chloramphenicol) and prevent transpeptidation and translocation leading to premature detachmenet of incomplete polypeptide chains
generally bacteriostatic
immunomodulatory effects (independent of antimicrobial effects)- inhibit chemotaxis and infilatrion of neutrophils into the airway, decreasing mucous secretion
inhbit production of numerous pro-inflammatory cytokines IL-1,6,8, TNFa
pro-kinetic effect on gi tract (motilin agonist)
191
What three classes of drugs irreversibly bind to the 50S ribosoome and prevent transpeptidation and translocation leading to premature detachment of incomplete polypeptide chains
Macrolides, Chloramphenicol, Oxazolidinones
192
Are macrolides bactericidal or bacteriostatic?
Generally bacteriostatic. can be -cidal at high concentration and against low inoculum of highly susceptible bacteria
anti-biofilm activity of some macrolides
193
What are the two immunomodulatory effects of macrolides?
1) Inhibit chemotaxis and infiltration of neutrophils into the airway which subsequently decreases mucous secretion
2) Inhibit the production of numerous pro-inflammatory cytokines (IL-1, IL-6, IL-8)
194
What group of antimicrobials have a pro-kinetic effect on the gi tract of dogs, horses, and cattle
Macrolides - direct motilin receptor agonist
Erythomycin in horses and dogs
Erythomycin, tylosin, tilmicosin in cattle
195
Erythromycin is a ______________
Macrolide (50S)
196
Clindamycin is a ______________
Lincosamide (50S)
197
What is the spectrum of activity of macrolides?
generally broad spectrum but best against gram + aerobes
Good gram + aerobes: bacillus, coryne, E. rhusiopathiase, Listeria, Staphylocccic, Streptococci, Gram - aerobes
Moderate: enterococci, some Bordetella, Haemophilus, Legionella, Ehrlichia, Pasteurella
Resistant: Enterobacteriacease, Pseudomonas, Nocardia, Mycoplasma, Chlamydia, Mycobacteri,
198
What are the three main mechanisms of resistance to Macrolides?
1) rRNA methylation*- prevents binding to the ribosome
2) Active drug efflux*-mediated by members of the ATP binding cassette family
3) Enzymatic inactivation- less common but due to esterase of phosphorylase inactivating enzymes
199
T/F macrolides are widely distributed to all tissues of the body
F- all tissues except those of the CNS
200
What macrolides are inhibitors of cytochrome p450
-Erythromycin and tiamulin
201
What macrolides do not inhibit cytochrome p450
-Clarithromycin and azithromycin
202
Clarithromycin is a ______
Macrolide (50S)
203
azithromycin is a _______
Macrolide (50S)
204
tiamulin
Macrolide (50S)
205
Tylosin is a_________
Macrolide (50S)
206
Macrolides adverse effects
*generally low, irritation, phlebitis
GI disturbance but can be life threatening in horses
207
Erythromycin is horses can lead to__________
clostridium overgrowth and serious diarrheic illness/death
208
Tilmicosin can result in___________ in species other than cattle and swine
cardiovascular toxicity
209
What is the drug of choice for Campylobacter diarrhea or abortion
Erythromycin
210
Macrolide clinical application
-Camplyobacter diarrhea/abortion (erythromycin)
-Penicilin-alternative to sensitive animals with gram + aerobes
-Ampicillin or Amoxicillin alternative in the treatment of leptospirosis
-Tetracycline alternative for rickettsial infection
211
What classes have mycoplasma spp activity
-Tetracycline, Fluoroquinolones, Chloramphenicol, Some macrolides/lincosamidesLincos
212
Tylosin
a macrolide used for treatment of local and systemic infections caused by mycoplasmas, gram + bacteria, anaerobes, and some respiratory gram - pathogens
213
Tilmicosin
a macrolide that is used only in cattle (injected) and swine (medicated feed) for respiratory disease
214
What is used in swine for the control/treatment of Brachyspira hyodysenteriae an mycoplasmal arthritis
Tiamulin (a macrolide)
215
Clarithromycin
a macrolide that is the drug of choice for treating Rhodococcus equi when combined with Rifampin
216
Tulathromycin
a long-acting, single-dose macrolide used for the treatment of respiratory disease in cattle and swine
accumulated in lung tissue
called Draxxin
217
Pirlimycin is a ______
lincosamide
218
Are Lincosamides bacteriostatic or bactericidal
both depending on the concentration, bacterial species and inoculum of bacteria
219
What is the mechanism of action of lincosamides?
Bind to the 50S ribosomal subunit (same site as macrolides) and inhibit peptidyl transferase
220
What are Lincosamides active against?
Gram + aerobes
mycoplasma
Anaerobes
221
Lincosamides are widely distributed with excellent penetration of________
bone and soft tissues, including tendon sheaths
low levels in the CNS
222
Lincosamide toxicities
Horses,Rabbits, hamsters, guinea pigs: necrotizing enterocolitis from toxigenic Clostridia
Salmonellosis in dogs
Neuromuscular blockage at high doses when given with anesthetics
223
Why might you give Clindamycin?
use in dogs/cats for periodontal disease, osteomyelitis, dermatitis, and deep soft tissue infections caused by gram positive aerobes and anaerobes. also for toxiplasmosis
224
Why might you give Lincomycin?
Ised in swine for swine dysentery, staphylococcal, streptococcal, and mycoplasmal infections
225
Why might you give Pirlimycin
used for udder infusion produce for treatment of bovine mastitis caused by gram positive cocci
226
What is mechanism of action of Sulfonamides?
inhibit dihydropteraste synthesase -inhibit the formation of pteroic acid - false substrate/competitive inhibitor
interfere with folic acid synthesis
227
Are Sulfonamides bacteriostatic or bactericidal?
Bacteriostatic
228
What is the spectrum of sulfonamides?
broad spectrum for bacteria and protozoa (Toxoplasma and coccidia)
best against gram + aerobes
moderate agaainst Staphyloccic, some gram - aerobes such as enterbacteriacea
Resistant: Mycobacterium, Mycoplasma
229
T/F Sulfonamides have mycoplasma activity
F
230
How are sulfonamides selective to killing microorganisms
animals take up preformed folic acid while bacteria synthesize folic acid
folic acid required for purine biosynthesis
231
What two ways does sulfonamide resistance occur?
1) Production of insensitive dihydropteroate enzyme
2) Hyperproduction of PABA (antagonizes sulfonamide
232
How are sulfonamides absorbed?
orally
233
What antimicrobials form crystals in the urine in acidic environments
Sulfonamide crystals
234
What are the toxicities from sulfonamides?
1) Urinary tract (Crystalluria, hematuria, leukopenia)
2) Hematopoetic disorders (Thrombocytopenia, anemia, leukopenia)
3) Dermatologic reactions (epidermal necrolysis)
4) KCS
5) Dogs- drug fever (doberman pinschers)- KCS, feverm arhtropathy, epistaxis
235
What dog species should you avoid Sulfonamides in?
Doberman Pinschers
236
Why do dogs experience longer half lifes and altered metabolites when given sulfonamides?
Because they are deficient in N-acetylation
237
Priming dosing of sulfonamides
used when initiating sulfonamide treatment
administer maintenance doses that are half the priming dose at intervals that are equal to half life of drug
238
Why should sulfonamides be only given IV
because of the alkalinity of parenteral formulations
239
What is added synergistically to sulfonamides
diaminopyrimidines because they interfere with folic acid production through a different mechanism
240
How does the mechanism of diaminopyrimidines differ from sulfonamides
Sulfonamides: Dihydropteroate synthetase
Diaminopyrimidine: Dihydrofolate reductase
241
Are diaminopyrimidines bactericidal or bacteriostatic
Bacteriostatic
242
How do you make Sulfonamides bactericidal?
Add a diaminopyrimidine like Trimethoprim
243
What blocks dihydrofolate reductase
Diaminopyrimidines like trimethoprim
244
Ormetoprime is a_______
Diaminopyrimidine
245
Pyrimethamine is a ______-
Diaminopyrimidine
246
Potentiated Sulfoamide spectrum of activity
good against aerobes (gram + or -)
some gram - anaerobes
resistant: rickettisa, leptospira, P. aerginosa, Mycoplasma
247
Rifampin mechanism of action
inhibit RNA synthesis by binding of Beta subunit of DNA-dependent RNA polymerases
more active in gram + bacteria and mycobacterium
248
HOw does Rifampin resistance occur
single mutation of B subunit of DNA dependent RNA polymerases
249
What is treatment of choice for foals with Rhodococcus?
Rifampin
250
Oxazolidinones mechanism of action
binds to 23S ribosomal RNA of the 50S subunit
251
Oxazolidonones
antibiotic that binds to 50S subunit to block protein synthesis
high oral absorption
sparingly use - not routine
252
Bacitracin
antibiotic that is a complex mixture of polypeptides that blocks phosophorylase reaction used topically and often combined with polymyxin B, neomycin or zinc
253
Methenamine
antibiotic that is a urinary antiseptic used to treat UTIs. at acidic pH in urine breaks down to form formaldehyde and ammonia. Enhanced activity with acidity. Do not use with sulfonamides or crystals will form
254
What effects the efficacy of a parasiticide?
1) Toxicity (dosage)
2) Ability to reach the parasite (Biology, timing, route of admin)
255
What is good parasiticide practice?
correct use of compounds where application at recommended odsage
observation of residues and withholding times
256
Why are withholding times critical for parasiticides?
for milk and meat animals intended for human consumption
-typically longer for bolus formulations
-Relative to other benzimidiazoles, thiabendazole is excreted rapidly
257
Relative to other benzimidiazoles, what is excreted rapidly?
Thiabendazoles
258
General mechanisms of parasiticides
1) Paralysis by stimulating or inhibiting neurotransmission (cholinergic agonist, GABA agonist, glutamate-gated Cl- channels)
2) Altered metabolic processes (inhibition of tubulin- helminths, inhibition of folic acid synthesis, inhibition of chiting fomration
3) Altered parasite repro (inhibition of protozoan replication
259
What is the mechanism of action of Benzimidazoles?
impairment of microtubule polymerization (tubulin) , interference with microtubule-mediated transsport of secretory vesicles in parasite absorptive tissues
leads to impaired cell structure, integrity, or metabolism
260
What is the mechanism of action of Tetrahydropyrimidines
causes paralysis of helminths through nicotinic cholinergic receptor agonist at the NMJ leading to sustained muscular contraction and tonic paralysis
261
What is the mechanism of action of Macrocyclic lactones
causes paralysis of helminths by binding to glutamate-gated chloride channels in nematode and arthrpod nerve cells. Channels open, allowing influx. Paralysis to pharnyx, body wall, and uterine muscles of nematodes
Flaccid paralysis
262
What does Benzimidazoles target?
Nematodes, Trematodes, +/- cesotdes
263
What do macrocyclic lactones target
nematodes, ectoparasites
264
T/F macrocyclic lactones need to be at high concentration to be effective
F- broad spectrum endectocides with activity at low levels
265
Macrocyclic lactones
-Paralysis by binding glutamate-gated chloride channels (flaccid paralysis)
-Nematodes and ectoparasites
-Broad spectrum at low dosing levels
-Least toxic, highly effective (receptor sites not normally in CNS)
-From Streptomyces
May have activity against immature life stages
1)Avermectins (Ivermectin, Eprinmectin, Doramectin, Selamectin)
2) Milbemycin (Moxidectin and Milbeycin Oxime)
3) Spinosyns (Spinosad and Spinoteram)
266
Avermectins like Ivermectin, Eprinomectin, Dorsmectin, and Selamectin are in what class of parasiticide?
Macrocyclic lactones
267
Milbemycins like Moxidectin and Milbemycin Oxime are in what class of parasiticide?
Macrocyclic lactones
268
Spinosyns like Spinosad and Spinoteram are in what class of macrocyclic lactones?
Macrocyclic lactones
269
Advantage Multi, Heartgard, and Cydectin are products that are
Macrocyclic lactones
270
What parasites are targeted by macrocyclic lactones?
nematodes and ectoparasites
271
Benzimidazoles
impairement of microtubulin (tubilin)
first class of modern anthelmintics
borad spectrum of activity, particularly against nematodes
usually given orally as paste, suspension, bolus
wide margin of safety, rapid elimination
272
What group of parasiticides end in-azoles
Benzimidazoles
273
Albendazole, Oxibendazole, Fenbendazole, Oxfendazole, Mebendazole, Thiabendazole, and Febentel is in what group of parasiticides
Benzimidazoles
274
What do Benzimidiazoles target
Nematodes
Trematodes
+/- cestodes
275
Triclabendazole is a benzimiadazole that has effect on trematodes but no effective on _________
nematodes
276
What do you give for treating Fasciola hepatica infection
Clorsulon (a Benzene Sulfonamide)
277
What parasites do Benzene Sulfonamides target
Tapeworms
Trematodes
278
What time frame are flukes susceptible to Benzene Sulfonamides?
2-3 months after infection
more difficult to treat later as they are walled off by connective tissues
279
What is the mechanism of action of Benzene Sulfonamides?
inhibit enzymes in glycolytic pathway of cestodes and trematodes
280
Tetrahydropyrimidines
Pyrantel salts - GI Nematodes
cause paralysis through nicotinic receptor agonist at the NMJ and sustained muscular contraction and tonic paralysis
high degree of safety, some may be teratogenic
Pyrantel pamoate (horse, cat, dog)
Pyrantel tartate (horse)
Morantel (Cows, goats)
should be kept out of direct sunlight
PO administration
281
Pyrantel tartrate, Pyrantel pamoate, and Morantel are examples of _______
Tetrahydropyrimidines "Pyrantel Salts"
282
Prazinoisoquinolones mechanism of action
not well understood but tegumental damage and paralytic muscular contraction of cesotdes leads to rapid death and explusion
reduced uptake of glucose, depletion of energy reserves
283
What species does Prazinoisoquinolones target
Cestodes and trematodes
284
Epsiprantel and Praziquentel are examples of
Prazinosioquinolones
285
Prazinoisoquinolones
targets cestodes and trematodes
Epsiprantel (Taenia, Dipylidium caninum) and Praziquantel (Taenia, Dipylidium caninum, Echinococcus in small animals- if oral can do Moniezia, Anoplocephala perfoliata and poutry)
286
Arsenicals
parasiticides that are hepato and nephrotoxic (monitor during therapy)
rapidly absorbed after intramuscular injection
ex: Melarsomine dihydrochloride
MOA not well understood
287
What is an advantage of Praziquantel or Epsiprantel
In addition to targeting Taenia and Dipylidium caninum, it has additonal activity againast echinococcus
288
What drug inhibits fungal mitosis?
Griseofulvin
289
What drug inhibits fungal RNA and protein synthesis
5-Flucytosine
290
What drug inhibits fungal protein synthesis?
Sardarin and 5-flucytosine
291
Cell membrane active antifungals target___________
ergosterol
292
Terbinafine
an allylamine (inhibits synthesis of ergosterol, the cell membrane of fungus, via inhibiting squalene epoxidase)
Broad spectrum and effective against dermatophytes, yeasts, Aspergillus, and dimorphic fungi
Fungicidal- kills fungus
Oral and topical
inhibitor of some CYP450 enymes
293
What is the mechanism of action of Terbinafine
an allylamine: inhibition of squalene epoxidase (blocks formation of ergosterol)
294
Is Terbinafine fungicidal or fungistatic?
fungicidal
295
Naftifine
an allylamine: inhibition of squalene epoxidase blocking the formation of ergosterol
broad spectrum, effective against dermatophytes, yeasts, Aspergillus, dimorphic fungi
296
What increases the clearance of Terbinafine?
Rifampin (Terbinafine is an inhibitor of some CYP450 enzymes)
297
Amphotericin B
A polyene: Fungicidal by binding to ergosterol, causing cell leakage and cell death
primarily for systemic fungal treatments, broad spectrum
Resistance develops slowlu
Binding to mammalian cell cholesterol makes it the most toxic of the clinically used antifungals in vet med
298
What two drugs are allylamine and inhibit squalene epoxidase- blocking the formation of ergosterol?
Terbinafine and Naftifine
299
What is the most toxic of the clinically used antifungals in vet med and why?
Amphotericin B because of binding to the mammalian cell cholesterol
300
What is the only FDA approved anti-fungal for ophthalmic use?
Natamycin (a polyene)
301
what is the mechanism of action of polyenes like Amphotericin B, Nystatin, and natamycin (pimaricin)?
fungicidal by binding to ergosterol, causing cell leakage and cell death
302
How do you administer Amphotericin B?
not well absorbed from the GI tract
administered IV- binds to cell mebranes and lipoproteins
Slowly distributed to most tissues except those of the CNS, eyes, and bone. accumulates in the liver, kidneys and lungs
lipid formulations are taken up by mononuclear phagocytes (and transported to the sites of infection) with lower renal concentrations, longer half life and less nephrotoxicity
303
What is used synergistically with Amphotericin B to decrease toxicity
Flucytosine
304
What is a serious side effect of Amphotericin B
Nephrotoxicity: Renal vasoconstriction, decreased glomerular filtration, and damage to the tubular epithelium
Must monitor weekly during therapy
lose concentrating ability, hypokalemia, hypomagnesemia, and red / white blood cells, albumin, and tubular casts appearing in the urine
305
What formulations of Amphotericin B have lower accumulation in the kidneys and reduced nephrotoxicity
liposomal or lipid-complexed formulations
because they are taken up into mononuclear phagocytic cells
306
What 3 drugs are polyenes and therefore are fungicidal by binding to ergosterol?
1) Amphotericin B
2) Nystatin
3) Natamycin (pimaricin)
307
What is the mechanism of action of Antifungal -azoles (Imidazole and Triazole)?
they target fungal cytochrome P450-Cyp51p by binding to lanosterol 14a-demthylase to inhibit ergosterol synthesis. Structural differences in azoles dictate the binding site on the CYP system: antifungal potency, spectrum of activity, bioavailability, drug interactions, and toxic potential
308
Are antifungal -azoles fungistatic or fungicidal?
Fungistatic
309
Do Imidazoles or Triazoles have a greater adverse effects
Imidazoles- endocrine adverse effects through cholesterol inhibition
Triazoles have less effect on mammalian P450
310
Miconazole, Clotimazole, Ketoconazole, itraconazole, fuconazole, and voriconazole are all:
Triazoles and Imidazoles that are fungistatic by inhibiting ergosterol synthesis
311
Whay are the uses of triazole and imidazoles?
broad antifungal spectrum of activity for systemic mycoses, yeats, and dermatophytes
Very limited resistance
312
What antifungal -azoles penetrate the CNS very well?
Fluconazole and Voriconazole
313
What antifungal -azole would you use for fungal cystitis because it is excreted in urine as an active drug ?
Fluconazole
314
Fluconazole
A triazole that is fungistatic by inhibiting ergosterol synthesis. has less effect on mammalian p450s than imidazoles
readily absorbed orally
only -azole that is excreted in urine as an active drug an is useful for fungal cystitis
315
What are the worries with giving Ketoconazole?
Azoles may be inhibitor or substrate of CYP system
1) inhibit which leads to accumulation of other co-administered drugs, hepatic dysfuncton, anorexia, vomiting, diarrhea
2) Suppression of adrenal or gonadal steroids (testosterone). may cause fetal death causing abortion/stillbirths
3) Reversible lightening of haircoat coloration and alopecia
4) Hepatotoxicity in cats is a risk
316
Is Fluconazole or Ketoconazole better tolerated?
Fluconazole
317
What considerations should you make when giving -azoles to pregnant animals?
Just. dont give them, avoid all systemic use
318
Is itraconazole or ketoconazole better in cats?
itraconazole
319
How is Ketoconazole administered?
orally to treat systemic mycotic infections (controlling coccidioidomycosis, blastomycosis, histoplasmosis) and dermatophytosis
320
What is the treatment of chouce for cryptococcosis and some disseminated mycoses such as coccidioidal meningitis)
Fluconazole
321
What has the broadest spectrum of activity of all the -azoles?
Voriconazole
also has increased activity against aspergillosis
322
Griseofulvin
Fungistatic: inhibits mitosis (slow action)
Effective only as systemic agent against dermatophytes
Resistance is rare
distributes to keratin precursor cells
Metabolized by liver
Cats more susceptible to toxic effects (Leukopenia+anemia in kittens, teratogenic, altered spermatogenesis)
323
What antifungal is only used systemically against dermatophytes
Griseofulvin
324
What is Griseofulvin's mechanism of action
inhibits mitosis of fungus (fungistatic)
325
Is Griseofulvin fungistatic or fungicidal?
Fungistatic
326
Where does Griseofulvin distribute to?
Keratin precursor cells
327
What are concerns with Griseofulvin?
1) Leukopenia and anemia in kittens with high doses
2) Do not give in animals with impaired liver function
3) Contraindicated in pregnant animals because it is teratogenic
4) Altered spermatogenesis
328
What 3 types patients should you not give Griseofulvin to?
Impaired hepatic function
Pregnant
Food producing animals
329
How should you treat Candida infections?
Amphotericin B or Fluconazole
Alternative Itraconazole
330
Why are all antiviral drugs virustatic?
because they must inhibit viral replication without destroying the host cells
331
Pharmacokinetic requirements of antiviral drugs must include what two things
Intracellular and nuclear penetration
332
Do antiviral drugs tend to have a narrow or wide spectrum of activity?
Narrow
333
How do antiviral protease inhibitors work
they block the activity of viral proteases that function in the assembly of viral components into a viron before release from the host cell
334
Amantadine and Rimantadine
act on early step of viral replication after the attachment of the virus to cell receptors
Inhibits replication of influenza A and C virus, Sendai virus , absorbed from GI tract
Few side effects, most are CNS
Block the uncoating of the virus
335
What are the main uses of Amantadine and Rimantadine
inhibiting the replication of influenza A and C virus
*Block uncoating of the virus (antimembrane drugs)
336
Idoxuridine (IDU)
a nucleoside analog, inhibit viral DNA/RNA synthesis, that is effective for the treatment of herpesvirus infection of the superficial layers of the cornea (herpesvirus keratitis) and of the skin, but is toxic when administered systemically
337
How should you treat herpesvirus keratitis
Idoxuridine (IDU), do not use systemically
or Trifluridine
338
Acyclovir
an antiviral that is phosphorylated by virus-induced thymidine kinase, better substrate and inhibitor of viral rather than cellular DNA polymerase
Relatively safe good for herpesvirus
ophthalmic ointment, topical ointment and cream, IV preparation, various oral formulation
339
Ribavirin
a synthetic triazole nucleoside (guanosine analog) with a broad spectrum of activity against many RNA and DNA viruses, both in vitro and in vivo.
-inhibit viral associated enzymes, capping of viral mRNA, and inhibition of viral polypeptide synthesis
Well absorbed
Narro margin of safety in domestic animals
admin by topical, parenteral, oral, and aerosol routes
340
What is the mechanism of Ribavirin
-inhibit viral associated enzymes, capping of viral mRNA, and inhibition of viral polypeptide synthesis
341
Interferons mechanism of action
activation of cellular endonucleases that degrade viral mRNA
also modulate the immune system of the host
inhibit the replication of a wide variety of viruses
not yet been found to be clinically useful because of their toxicity
342
What do neuraminidase inhibitors do
they enzymatically cleave sialic acid residues which is required to release newly formed virus particles from infected cells. ultimately blocking the virus
effective against influenza A and B
343
What are neuraminidase inhibitors active against?
influenza A and B
344
Zanamivir and Oseltamivir are examples of
neuraminidase inhibitors (an enzyme that cleaves sialic acid residues)
useful for the treatment of influenza A and B
345
Zanamivir
Relenza
A neuraminidase inhibitors that is active against both influenza A and B
topical treatment
Reduce period of flu symptoms by 1 day. Improved flu symptoms within 2 days
346
Oseltamivir
Tamiflu
A neuraminidase inhibitors that is active against both influenza A and B
Reduces severity of flu symptoms by 40% and also reduces rates of secondary complications
reduced infection of patients contacts by approximately 89%
347
Name the two neuraminidase inhibitors
Zanamivir (Relenza)
Oseltamivir (Tamiflu)
348
What does Lysine (Enisyl-F) reduce the frequency and severity of?
FHV-1
349
How does Lysine reduce the frequency and severity of FHV-1
Herpes virus requires arginine and lysine may interfere with the absorption of arginine in the intestine via a high lysine/arginine ratio in the diet
350
What in the diet can interfere with the absorption of arginine, which herpesvirus requires?
Lysine
351
What is the major non-psychoactive Cannabinoid?
Cannabidiol (CDB)
352
What is the major psychoactive Cannabinoid
THC (-delta nine-tetrahydrocannabinol)
353
What Schedule drug is marijuana?
Schedule I controlled drug
"No currently accepted medical use and high potential for abuse" - DEA
354
CB1 and CB2 receptors are what types of receptors?
G protein-couple receptors
355
Endocannabinoid system
a system that has autocrine and paracrine activity
neurotransmitors that are agonists on CB1 receptors (anandamide) and CB2 receptors (2-arachidonoylglycerol)
synthesized from mebrane lipids
not stored in pools (e.g vesicles)
locally produced, local action
can be classified as autacoids
much less potent
356
What receptor of the endocannabinoid system has effects on cognition
CB1
357
CB1 receptors
CNS
presynaptic G protein coupled receptor
glutamatergic and GABAergic neurons
activation=decrease in neurotransmitter release
358
What receptor of the endocannabinoid system has effects on peripheral immune cells
CB2
359
What endocannabinoid receptor decreases cAMP and increases MAPK on peripheral immune cells when activated ?
CB2
360
What receptor of the endocannabinoid receptor decreases neurotranmission release when activated?
CB1
361
Where are CB1 receptors located
mostly in the nervous system and brain
362
What effects do CB2 receptors have?
-inflammation and chronic pain
-inhibits pro-inflammatory cytokine production
-immunomodulation (immunosuppression)
*theapeutic cannabinooid receptor
363
T/F THC has high affinity for both CB1 and CB2 receptors
T, CB1 effect more than CB2 but high for both generally
364
T/F CBD has a low affinity for CB1 and CB2 receptors
T, but can act synergistically with THC to modulate pain through pathways
365
T/F CBD has no anti-inflammatory effects
F
366
What are the potential therapeutic uses of CBD
1) Anti-emesis (if unresponsive to 5-HT3 agonists like ondansetron)
2) Diabetes mellitus- reduces pancreatic inflammation and via antioxidant effects
3) Cancer- reduce neoplastic proliferation in select tumor cell lines
4) Antibacterial?
5) Pain, inflammation, and immunomodulation- acute/chronic pain, decrease Tcell activity, arhtritis and psoriasis
6) Epilepsy- anti-epileptic effects
7) anxiolytic- exerts benzodiazepam-independent anxiolytic activity by modulating 5-HT1a receptors possibly
367
T/F CBD products are regulated
F
368
What cannabinoid receptor dominates toxicity?
CB1
369
Signs of Cannabinoid toxicity in dogs
1) Ataxia, incoordination
2) Depression, disorientation
3) Mydriasis
4) Hypothermia
5) hypersalivation
6) Bradycardia
370
Static ataxia
associated with THC toxicity- loss of ability to maintain fixed position due to binding of CB1 agonist in cerebellum affecting movement control
371
How to treat cannabinoid toxicity
no specific antiote
supportive measures (sedatives, antiemtics, IV fluids as neccessary
Activated charcoal may reduce half life
372
What systems can trigger emesis
1) CNS input (gross, smells, thoughts)
2) Vestibular apparatus (motion sickness, vestibular disease, inner ear infections)
3) CRTZ- chemo receptor trigger zone (drugs, toxins, pH, metabolites)
4) GI tract signals (inflammation, irritation, stimulation, constipation)
373
What can Apomorphine be used for
drops in conjunctiva or IV to induce emesis
IV- give it in back leg because it works really quickly
373
What is Apomorphine's mechanism of action
dopaminergic receptor agonist (D2) to trigger the chemoreceptor trigger zone for emesis
374
How can you give apomorphine
in the conjunctiva or IV (back leg)
375
Why should you not use apomorphine in cats?
cats do not dopaminergic receptors in their chemoreceptor trigger zone but have them elsewhere so they will not induce emesis
376
T/F Apomorphine is used to induce emesis in cats
F- they do not have dopaminergic receptors in their CRTZ
377
Ropinirole (Clevor)
eye drops used to induce emesis in dogs
378
What can Ropinirole be used for?
Inducing emesis via eye drop
379
Anti-Emetics do:
Antagonist for receptors in the chemoreceptor trigger zone
380
What stimulates NK1 receptors for emesis?
Substance P
381
Maropitant (CWhaerenia) mechanism of action
It is an NK1 receptor antagonist and prevents emesis
382
What is Cerenia's name
Maropitant
383
Why is Maropitant so effective at preventing emesis
There are NK1 receptors in the chemoreceptor trigger zone and the gastrointestinal tract so it able to antagonize both
384
What drug is a neurokinin-1 receptor antagonist
Maropitant (Cerenia)
385
Maropitant is well tolerated in dogs and cats, but in both species it may cause ___________ during injection
pain/vocalization
386
Ondansetron (Zofran) is a __________ receptor __________
Ondansetron (Zofran) is a 5-HT receptor antagonist
387
Ondansetron is well tolerated in dogs and cats but adverse effects may include __________
1) Constipation
2) Sleepiness
3) Head-shaking
388
What does the parietal cell do
Secrete HCl into the stomach via a protein pump under the H2 receptor
389
What 2 drugs can you use to reduce gastric acid secretion?
1) Famotidine (H2 receptor antagonist)
2) Omeprazole (proton pump inhibitor)
390
What drug is an H2 receptor antagonist, resulting in reduced gastric acid secretion
Famotidine
391
What drug inhibits proton pumps in the stomach, resulting in reduce gastric acid secretion?
Omeprazole
392
Is omeprazole famotidine better at raising gastric pH
Omeprazole (proton pump inhibitor)
393
What are some adverse gi effects of dogs receiving oral omeprazole
1) Reduced fecal quality 9more liquid)
394
Is omeprazole dosed once or twice daily for best efficacy
twice
395
What is the most efficacious way to administer omeprazole
reformulated paste (RP)
396
What are some ways to get cats to eat?
1) try canned food
2) Warm it up
3) Soak kibble in tuna juice
4) Bowls that dont hurt whiskers?
5) acupuncture
Drugs:
Cyproheptadine
or
Mirtazapine
or Gabapentin
397
What is the mechanism of action of Cyproheptadine
antihistamine (serotonin antagonist) that has a side effect of stimulating appetite
398
Is Cyproheptadine really used anymore in vet med for appetite stimulation?
nah. Mirtazapine is pretty og
399
What is Mirtazapine used for
appetite stimulant (side effect)
anti-anxiety, antidepressant
imrproves rats sexual motivation test
-Anti-emetic (anti-nausea) 5-HT3 antagonist
400
What is the mechanism of action of Mirtazapine
5-HT3 antagonist (anti-emetic)
good for appetite stimulation
401
T/F you can give Cyproheptadine with Mirtazapine for appetite stimulation synergy
F- don't give together
one is antidote for the overdose of the other
402
Mirataz is a ________
transdermal form of mirtazapine that is used for appetite stimulation is kitty cats
403
What is the result of oral diazepam as use for appetite stimulation is cats
Fulminant hepatic failure
DO NOT USE ORAL DIAZEPAM
Okay to give IV diazepam though
404
Ghrelin
a hormone that is secreted to tell you to eat. elevated when hungry
405
Leptin
a satiety hormone that tells you are full.
hormone made by adipose
elevated when full
406
Mirtazapine (Entyce)
A ghrelin receptor agonist that stimulates the hypothalamus to increase hunger
Stimulates the pituitary gland
407
Capromorelin
orally active ghrelin agonist that caused sustained increases in IGF-1, increased food intake and body weight in cats
408
Gabapentin
used to calm down stressed cats before the vet
side effect: increased in appetite and good at stimulating appetite
409
What is the route of choice for ondansetron
IV- poor oral bioavailability
410
Loperamid (imodium)
binds u opioid receptors in the myenteric plexus of the large intestine
decreases the activity of the myenteric plexus, decreasing longitudinal and circular intestinal smooth muscle
411
What is the side effect of opioid induced constipation, like from Loperamide (Imodium)
Constipation
412
What is Loperamide's (Imodium) mechanism of action
binds u-opioid receptors in the myenteric plexus of the large intestine to decrease longitudinal and circular intestinal smooth muscle
413
What are the two major types of small intestine motility
1) peristalsis (propulsion)
2) Segmentation (mixing)
414
What mimics the motilin component on muscarinic receptor for GI motility
Erythromycin
415
What mimics the role of Serotonin on 5-HT4 receptors for gut motility
Cisapride
416
What 3 things can increase GI motility by increase ACh release at the cholinergic motor neuron?
1) Serotonin (5-HT4) -mimic by Cisapride
2) Motilin (hormone) - mimic by erythromycin
3) Dopamin antagonist (Metoclopramide)
417
Metoclopramide
increase GI motility (via dopamine antagonist) via increase tone of GI contrations, relaxed pyloric sphincter, increases duodenal/jejunal peristalsis
decreased time to empty stomach/GI transit time
increase LES P and reduce gastresophageal reflux
-only on the small intestine
little to no effect on the colonic motility
418
Where in the intestine does Metoclopramide act to increase GI tract movement
only small intestine and constant rate of infusion
little to no effect on colonic motilty so rarely used
419
Metoclopramide mechanism of action
Dopamine antagonist leading to increase ACh release onto GI smooth muscle
this enhances GI motility but only in the small intestine
420
Cisapride mechanism of action
Serotonin (5-HT4) agonist to increase release of ACh onto GI smooth muscle
happens in colon and small intestine
421
What is the drug of choice for moving a cat's colon
Cisapride is the drug of choice for moving a cat's colon
422
How do you treat inflammatory bowel disease
reduce the antigenic stimulation and resulting inflammation
1) Hypoallergenic/hydrolyzed diet
2) Prednisolone
423
If a cat has a problematic liver, what glucocorticoid should you give to treat IBD?
Prednisolone (not prednisone) because it is the active compound, skipping the need for conversion by the liver
424
What do you get at higher doses of glucocorticoids
Immunosuppression (Anti-inflammatory at lower doses)
425
Budesonide
a glucocorticoid that predominately acts on GI tract and gets inactivated before reaching other parts of the body
via first pass hepatic metabolism
decreases systemic steroid effects
no better than prednisone for clinical response to IBD
426
What is a glucocorticoid that predominately only acts on the GI tract
Budesonide
427
Cobalamin absorption
Vitamin B12
enters into stomach
separated from food stuffs
attached to R protein
joins with intrinsic factor (produced by pancreas)
transports cobalamin to distal small intestine where transcobalamin can move it into the bloodstream
428
What is needed for the absorption of vitamin B12/Cobalamin
intrinsic factor from the pancreas
429
How do you treat chronic copper hepatopathy in dogs
Penicillamine to absorb and bind copper
430
how do you treat acute neutrophilic cholangitis in cats
Clavamox, antibiotic
431
One way should you treat vomiting in a dog
Cerenia (maropitant)
432
One way you should treat nausea in a cat
Omeprazole (proton pump inhibitor)
433
one way you should increase appetite in cats
Mirtazapine (synthetic ghrelin)
434
