LEC 18, 19 - Inhibitors of Protein Synthesis Flashcards
What are the adverse effects of tetracyclines?
Nephrotoxic
Staining of unerupted teeth
Superinfections
GI upset
Anti-anabolic
Photosensitivity
Hepatotoxicty
What animals is gentamycin used in?
Pigs, but no other food animals
Tetracyclines (5)
Doxycycline
Minocycline
Tetracycline
Oxytetracycline
Chlortetracycline
How do ionophores work?
Complex with Na+ in cell membrane
Produce passive extracellular transport of K+
Intracellular influx of H+
Kills bacteria + coccidian by lowering intracellular pH
Why is there sometimes an anti-anabolic effect with the use of tetracyclines?
high doses cause binding to mitochondrial ribosomes
Elevated BUN with pre-existing renal disease
How is linezolid metabolized?
Oxidation but it is non-enzymatic and does not involve hepatic microzome system
how is neomycin used?
Orally for enteric infections (food animal)
Topically for skin + ear + eye infections
What are tetracyclines used for in small animals medicine?
Respiratory + Urinary tract infections
Psittacosis in birds
How does linezolid work?
Inhibits bacterial protein synthesis by interfering with translation
Why is the use of lincosamides contraindicated in some animals?
Produce severe, often fatal diarrhea due to altered GI flora involving C. Diff
What animals is most sensitive to ionophore toxicity?
Horses
What is the basic structure of the aminoglycosides?
Contain amino sugars in glycosidic linkage
Polycations
How is chloramphenicol absorbed?
From GI tract and distributed to all tisuses including CNS and eye
What type of CNS infection is clindamycin used for?
Toxoplasma encephalitis
How are lincosamides adminstered?
PO + Paraenterally + Topically
What are the four major uses for linezolid?
Bacterial pneumonia
Skin/suture infections
VRE infections
MRSA infections
What are the regulations when it comes to the use of oxyteracyclines in food animals?
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
What impairs absorption of tetracylcines?
Divalent or trivalent cations
Avoid milk, antacids, or iron salts for three hours before and after administration
What are the ionophores derived from?
polyther from Streptomyces
What is the distribution pattern of florfenicol?
Widely distributed, including CNS
What does it mean when something has concentration dependent killing?
Increasing concentrations kill an increasing population of bacteria
More rapid
Adverse effect are time dependent
How is tylosine adminstered?
IM or PO, BID or SID - Swine + Calves + Lambs + Dogs + Cats
What situations are aminoglycosides most often used?
Gram-negative enteric bacteria
Suspicion of sepsis or endocarditis
What are the three ways that aminoglycosides interact with the 30s subunit causing the block of protein synthesis?
Block initiration of protein synthesis
Block further translation and elicit premature termination
Incorporation of incorrect amino acid
What is gentamicin and amikacin used against specifically?
Pseudomonas
Proteus
Staphylococcus
Corynebacterium
(Wider spectrum of activity)
What are the restrictions to absorption of erythromycin?
Gastric acids destroy base
need to modify formula for oral admin
Enteric coated or film-coated
What is pirlimycin used for?
Bovine mastitis
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
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
What ionophores are used for prevention of coccidiosis in broilers?
Salinomycin
Narasin
Why does erythromycin react with chloramphenicol and clindamycin?
All these drugs bind to similar spots on the 50s subunit
What is the basic structure of macrolides?
Macrocylic lactone ring which sugars are attached
What are the regulations of chloramphenicol use in food animals? Why?
ILLEGAL
Due to residue0induced toxicity in humans
Why does iatrogenic endotoxicosis occur with phenicol adminstration?
Rapid killing of gram (-) bacteria
What is lincomycin used for?
Swine - control/txt of swin dysentery
Treatment of:
Staphlococcal
Streptococcal
Mycoplasmal
…infectiosn
Aminoglycosides (7)
Neomycin
Gentamicin
Amikacin
Apramicin
Tobramycin
Plazomicin
How is clarithromycin administered?
PO, BID - Dogs + Cats + Ferrets
Oxazolidinones
Linezolid
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
What drugs should not be used with linezolid?
MAO inhibitors
How does plazomicin differ from the other aminoglycocides?
Devoid of nephrotoxic + ototoxic effects
Not influenced by bacterial enzymes that modify/inactivate aminoglycosides
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
What is tildipirosin used for?
BRD - Mannheimia haemolytica + Pasteurella multocida + Histophilus somni
Control of BRD - MH + PM + HS
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
What is used with clindamycin for preventative purposes? Why?
Metronidazole
Avoid C. diff-mediated pseudomembranous colitis associated with clindamycin in dogs
What is the mechanism of action for lincosamides?
Bind to 50S ribosomal subunits of bacteria = protein syntehsis inhibition
What are the three common tetracyclines used in small animals?
Doxycycline
Minocycline
Tetracycline
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