LEC 18, 19 - Inhibitors of Protein Synthesis Flashcards
1
Q
What are the adverse effects of tetracyclines?
A
Nephrotoxic
Staining of unerupted teeth
Superinfections
GI upset
Anti-anabolic
Photosensitivity
Hepatotoxicty
2
Q
What animals is gentamycin used in?
A
Pigs, but no other food animals
3
Q
Tetracyclines (5)
A
Doxycycline
Minocycline
Tetracycline
Oxytetracycline
Chlortetracycline
4
Q
How do ionophores work?
A
Complex with Na+ in cell membrane
Produce passive extracellular transport of K+
Intracellular influx of H+
Kills bacteria + coccidian by lowering intracellular pH
5
Q
Why is there sometimes an anti-anabolic effect with the use of tetracyclines?
A
high doses cause binding to mitochondrial ribosomes
Elevated BUN with pre-existing renal disease
6
Q
How is linezolid metabolized?
A
Oxidation but it is non-enzymatic and does not involve hepatic microzome system
7
Q
how is neomycin used?
A
Orally for enteric infections (food animal)
Topically for skin + ear + eye infections
8
Q
What are tetracyclines used for in small animals medicine?
A
Respiratory + Urinary tract infections
Psittacosis in birds
9
Q
How does linezolid work?
A
Inhibits bacterial protein synthesis by interfering with translation
10
Q
Why is the use of lincosamides contraindicated in some animals?
A
Produce severe, often fatal diarrhea due to altered GI flora involving C. Diff
11
Q
What animals is most sensitive to ionophore toxicity?
A
Horses
12
Q
What is the basic structure of the aminoglycosides?
A
Contain amino sugars in glycosidic linkage
Polycations
13
Q
How is chloramphenicol absorbed?
A
From GI tract and distributed to all tisuses including CNS and eye
14
Q
What type of CNS infection is clindamycin used for?
A
Toxoplasma encephalitis
15
Q
How are lincosamides adminstered?
A
PO + Paraenterally + Topically
16
Q
What are the four major uses for linezolid?
A
Bacterial pneumonia
Skin/suture infections
VRE infections
MRSA infections
17
Q
What are the regulations when it comes to the use of oxyteracyclines in food animals?
A
Cattle =
Extralabel Withdrawl time = 28 days for intrauterine treatment Test milk after intrauterine treatment
Sheep/goats =
Extralabel withdrawl time = 28 days IM/SC treatment
Milk withdrawl time = 96 hours
Swine =
Withdrawal time = 14 days
18
Q
What impairs absorption of tetracylcines?
A
Divalent or trivalent cations
Avoid milk, antacids, or iron salts for three hours before and after administration
19
Q
What are the ionophores derived from?
A
polyther from Streptomyces
20
Q
What is the distribution pattern of florfenicol?
A
Widely distributed, including CNS
21
Q
What does it mean when something has concentration dependent killing?
A
Increasing concentrations kill an increasing population of bacteria
More rapid
Adverse effect are time dependent
22
Q
How is tylosine adminstered?
A
IM or PO, BID or SID - Swine + Calves + Lambs + Dogs + Cats
23
Q
What situations are aminoglycosides most often used?
A
Gram-negative enteric bacteria
Suspicion of sepsis or endocarditis
24
Q
What are the three ways that aminoglycosides interact with the 30s subunit causing the block of protein synthesis?
A
Block initiration of protein synthesis
Block further translation and elicit premature termination
Incorporation of incorrect amino acid
25
What is gentamicin and amikacin used against specifically?
Pseudomonas
Proteus
Staphylococcus
Corynebacterium
(Wider spectrum of activity)
26
What are the restrictions to absorption of erythromycin?
Gastric acids destroy base
need to modify formula for oral admin
Enteric coated or film-coated
27
What is pirlimycin used for?
Bovine mastitis
28
What is the mechanism of action for tetracyclines?
Inhibition of bacterial protein synthesis
Bind reversibly to 30S ribosomes + prevent access of aminacyl tRNA to receptor site on mRNA-ribosome complex
Prevents addition of AA to growing peptide chain
29
How is resistance developed against eryhtromycin?
Active pump mechanism
Ribosomal protection by inducible or constitutive production of methylase enzymes = modification of ribosomal target
Macrolide hydrolysis by esterases
Chromosomal mutations that alter 50S ribosomal protein
30
What ionophores are used for prevention of coccidiosis in broilers?
Salinomycin
Narasin
31
Why does erythromycin react with chloramphenicol and clindamycin?
All these drugs bind to similar spots on the 50s subunit
32
What is the basic structure of macrolides?
Macrocylic lactone ring which sugars are attached
33
What are the regulations of chloramphenicol use in food animals? Why?
ILLEGAL
Due to residue0induced toxicity in humans
34
Why does iatrogenic endotoxicosis occur with phenicol adminstration?
Rapid killing of gram (-) bacteria
35
What is lincomycin used for?
Swine - control/txt of swin dysentery
Treatment of:
Staphlococcal
Streptococcal
Mycoplasmal
...infectiosn
36
Aminoglycosides (7)
Neomycin
Gentamicin
Amikacin
Apramicin
Tobramycin
Plazomicin
37
How is clarithromycin administered?
PO, BID - Dogs + Cats + Ferrets
38
Oxazolidinones
Linezolid
39
What are the restrictions for tildiprosin when using it with food animals?
Withdrawl time for meat - 21 days
Do not use in female cattle over 20 months
40
What drugs should not be used with linezolid?
MAO inhibitors
41
How does plazomicin differ from the other aminoglycocides?
Devoid of nephrotoxic + ototoxic effects
Not influenced by bacterial enzymes that modify/inactivate aminoglycosides
42
What are ways that resistance against aminoglycosides occurs?
Plasmid mediated chemical changes of enzymes that adenylate + phosphorylate + acetylate aminoglycoside drugs
Resistance may involve alteration of bacterial ribosomes which aminoglycosides attach
Cannot enter the cell
43
What is tildipirosin used for?
BRD - Mannheimia haemolytica + Pasteurella multocida + Histophilus somni
Control of BRD - MH + PM + HS
44
What side effects do you see in dogs, cats, cattle, and swine from the use of lincosamides?
Rare
Neuromuscular blockade at high doses or when used with anesthetics
45
What is used with clindamycin for preventative purposes? Why?
Metronidazole
Avoid C. diff-mediated pseudomembranous colitis associated with clindamycin in dogs
46
What is the mechanism of action for lincosamides?
Bind to 50S ribosomal subunits of bacteria = protein syntehsis inhibition
47
What are the three common tetracyclines used in small animals?
Doxycycline
Minocycline
Tetracycline
48
What is the mechanism of action for erythromycin?
Inhibition of protein synthesis of susceptible bacteria
Binds reversibly to 50S subunit to prevent translocation of AA
49
What is the major use of ionophores?
Poultry + swine feed efficiency + anticoccidial activity
50
What is clindamycin used for?
Dogs/Cats = Peridontal disease + osteomyelitis + dermatitis + deep soft tissue infections caused by gram + infections + TOXOPLASMOSIS
Dogs = Neoporosis
51
How is tilmicosin adminstered?
SC, every 72 hours - Cattle
52
What does it mean to have post-antibiotic effect?
Antibacterial activity persists beyond the time that the antibiotic is measurable
53
how does tobramycin compare to gentimycin?
More potent anti-pseudomonal activity + reduced nephrotoxicity
54
How do tetracyclines aid in contracted tendons in foals?
Inhibit collagen-based contractions in myofibroblasts
55
What do ionophores do within the rumen?
Select for Gram + bacteria, shifting the bacterial community to Gram (-)'s
This increases the production of propionic acid and decreases the production of acetic and butyric acids
56
What are the adminstration requirements for gamithromycin in food animals?
SC in beef and non-lactating cattle only
Not for use in female dairy cows over 20months of age or calves that will be used for veal
57
What specific bacteria do tetracyclines work against in small animal medicine?
Borrelia
Brucella
Haemobartonella
Ehrlichia
58
How is azithromycin administered?
SID, PO - Dogs + Cats + Foals
59
What are lincosamides active against?
Aerobic gram-positive cocci
Several anaerobic gram-negative/positive
60
Why should PO and parenterally admin be avoided in horses?
Danger of disrupting ruminal or colonic microflora
61
Which of the tetracyclines can pentrate the CNS, eyes, and prostate?
Doxycycline
Minocyline
62
How do aminoglycosides get into the cell?
Oxygen dependent transport
63
Why is it thought that tetracyclines work well with cat absecesses?
Contain L-form bacteria that lack cell walls and are sensitive to tetracyclines
64
What are the three important characteristics of aminoglycosides when it comes to their pharmokinetics?
None is absorbed after oral administration
None pentrate CSF readily
Normal kidney rapidly excretes them all
65
How do tetracyclines enter the bacterial cell?
Oxygen-dependent
66
When are tetracyclines used for cat abscesses?
Those that do not respond to B-lactams
67
What are the characteristics of distribution when it comes to erythromycin?
Passes through placeneta
Penetrates prostatic fluid
DOES NOT GO INTO CNS
68
Phenicols (2)
Chloraphenicol
Florfenicol
69
What is the protocol for Florfenicol in food animals?
Approved for use in cattle and swine
Respiratory disease + foot rot in cattle
70
What is the mechanism of action for chloramphenicol?
Reversibly binds to 50S subunti
Prevents transpeptidation
71
What are the five derivatives of erythromycin?
Tylosin
Tilmicosin
Tulathromycin
Azithromycin
Clarithromycin
72
Macrolides (6)
Erthyromycin
Gamithromycin
Tildipirocin
Lincomycin
Clindamycin
Pirlimycin
73
Why do tetracyclines tend to stain teeth?
Formation of tetracyclein-calcium phosphate complex in enamel and dentine
74
What is the predominant activity of linezolid?
Aerobic gram-positive organism
75
What are tetracyclines used for in large animals?
Local + systemic bacterial infections in sheep, cattle, horse, and swine
Feed additive/growth promoters in cattle and swine
76
What are the six groups of drugs that act as inhibitors on protein synthesis?
Aminoglycosides
Macrolides
Tetracyclines
Phenicols
Ionophores
Oxazolidinones
77
How is doxycycline secretion diifferent?
Intestinal excretion is major route of elimination
78
Which of the tetracylcines are not nephrotoxic?
Doxycycline
Minocycline
79
What is the veterinary feed directive?
Intends to limit antibiotic use for therapeutic needs instead of production
Recommends drug manufacturers VOLUNTARILY stop labeling drugs as "promoting animal growth"
80
What is the difference between monogastric and ruminal animals when it comes to ionophore absorption?
More complete and metabolism is slower = increased toxicity
81
What animals is lincosamides contraindicated in?
Horses
Rabbits
Hamsters
Guinea pigs
82
What do aminoglycosides act on?
Inhibiting protein synthesis of susceptible organisms
Inhibit funciton of the 30S subunit of bacterial ribosomes
83
What are the distribution characterisitics of clindamycin?
Crosses placenta
Gets into breast milk
Reaches high concentrations in teh bone
Does not get into the CNS
84
How are ionophores excreted?
Bile
Elminated by feces
85
What is a good way to get aminoglycocides to work against gram +'s?
Use with beta lactam
86
Which of the phenicosl produces aplastic anemias?
Chloramphenicol
87
What are the adverse effects of chloramphenicol?
Dose dependent
bone marrow depression
Gray syndrome
Due to inhibition of protein synthesis in host mitochondria
88
How is florfenicol metabolized?
1/3 metabolized by the liver
2/3 of drug excreted as parent
89
What is chloramphenicol used for in dogs, cats, horses, ad birds?
Local and systemic infections
Respiratory + CNS + Ocular
Due to Anaerobes + Salmonella
90
What are the adverse reactions to erythromycin?
GI upset
Pyresis
Reversible jaundice
Elevated hepatic enzymes
Allergic reactions
QT prolongation
91
How is florfenicol given to swine?
Drinking water
92
What is the absorption rate of tetracyclines? What is the exception?
60 to 90%
Cholortetracycline - 35%
93
When are macrolides effective?
Alternative agents to penicillin when patient is allergic and/or when in renal failure
94
What are the adverse effects of the penicols?
Anemia
Aplastic anemia
Iatrogenic endotoxicosis
95
How are tetracyclines excreted?
Glomerular filtration, with small amounts being excreted into the bile
96
How is erythromycin administered?
PO or IM TID - Dogs + cats + foals
IM SID - Cattle + Sheep + Swine
97
What does tetracycline work against?
Gram +/- aerobes/anaerobes
Rickettsiae
Spirochetes
Chlamydiae
Mycoplasma
Some protozoans
98
How is linezolid adminstered?
IV or Oral
99
What does plazomicin act against?
Klebsiella pneumoniae
Escherichia coliUse
100
What is the major characteristic of aminoglycocides that give them their properties?
Polarity
101
How is erythromycin excreted?
Lost in feces in large amounts
5% excreted in urine
102
What two drugs have contraindications with erythromycin?
Chloramphenicol
Clindamycin
103
What is gamithromycin used for?
BRD - Manneimia haemolytica + Pasteurella multocide + Histophilus somni + Mycoplasma bovis
Control of BRD - M.H. and P.M.
104
What are the characteristics of metabolism for tetracyclines? Which one differs and how?
Metabolism is very minimal in domestic animals
Exception = minocylcine, metabolized by the liver
105
How is florfenicol given to cattle?
IM, one dose than another 48 hours later
Slow-release prep
106
How is tulathromycin administerd?
one SC injection against cattle and swine respiratory infectiosn
107
What are the gram negative rods that aminoglycocides are most effective against?
Enterbacteria
Proteus
Psudomonas
Serratia
108
What ionophores are used in the feed for growth promotion and feed efficiency?
Monensin
Lasalocid
Laidlomycin
109
What are the three lincosamides?
Lincomycin
Clindamycin
Pirilmycin
110
What specific bacteria do tetracyclines kill in large animals?
Chlamydial
Rickettsial
Protozoal
111
What drug are lincosamides mixed with to treat toxoplasmosis?
Pryimethamine
112
When is chloramphenicol bacteriocidial?
Meningeal pathogens
H. Influenzae
Neisseria meningitidis
Streptococcos pneumoniae
113
How does chloramphenicol cause aplastic anemia in humans?
Idiopathic
Why it is banned in food products
114
What three tetracyclines are most commonly used in large animals?
Tetracycline
Chlortetracycline
Oxytetracycline
115
Ionophores (5)
Monensin
Lasalocid
Laidlomycin
Salinomycin
Narasin
116
When are aminoglycosides bactericidal?
Aerobic conditions, unknown why
117
What two tetracyclines are used for cat abscesses?
Doxycycline
Minocycline
118
Where do superinfections caused by tetracyclines tend to occur?
Gi tract
due to prolonged adminstration
119
How is chloramphenicol metabolized?
Glucuronide conjugation
75% for cats
90% for dogs
120
How should aminoglycosides be given since that have a large PAE?
Single, large dose will be the most efficective
121
Why does chloramphenicol cause anemia?
Dose-related
Inhibits the uptake of iron in mitochondira present in erythropoeitic cells in bone marrow
