Protein Synthesis Inhibitors (ribosomes Flashcards
Aminoglycosides
Gram- aerobes (pseudomonas, best drug)
Selected gram + aerobes (staph)
Combination therapy (with B-L)
Nocardia and atypical mycobacteria
Aminoglycosides structure- activity relationship
Weak base
Oxygen dependent
Resistance to obligate anaerobes
Aminoglycosides PK
Initiation of protein synthesis (bactericidal)
Concentration dependent (10x MIC)
Long post abx effect (once daily dosing)
How does pH affect aminoglycosides
Alkaline pH → enhanced efficacy
Acidic pH → trapped → ↓ oral absorption, milk and enhances renal toxicity
How do aminoglycosides interact with organs/ tissues
Water soluble, poorly lipid soluble
Limited passive diffusion through membranes
Poor distribution intracellularly, CNS and eye
Selectively binds to kidney, cochlea and vestibular apparatus (80-100 yrs t 1/2)
Aminoglycosides adverse effects
Toxicity dose related
Acute tubular nephrosis
Risk based on # of amines (+ charges)
Toxicity for cochlea and vestibular apparatus
Aminoglycoside neurologic effect
Neuromuscular paralysis (antagonized with neostigme or calcium)
Interferers with calcium flux and ACh release
How do Aminoglycosides affect cells in the cochlea and vestibular apparatus
Destroys sensory cells, irreversible damage
Ataxia, loss of balance, vertigo, high frequency hearing loss
Aminoglycosides compliance
ELDU discouraged but not prohibited
Approved aminoglycosides for food animals
Apramycin
Gram - infections
Pig and calves 28 day withdrawal
Gentamicin
Broad-spectrum, used with B-L, synergistic effects
Used for infections requiring aminoglycosides
Amikacin
Intrauterine for horses
Broad spectrum effective against ESBL producing E. coli
What is Amikacin used for?
Infections caused by E. coli, Klebsiella, pneumoniae and other multi-drug resistance bacteria
Apramycin use
In pigs for colibacilosis (pig scours)
Neomycin
Mostly topical or oral use
Local effect in the intestine
Treats enteritis caused by E. coli
Aminoglycosides resistance
Inherent: Obligate anaerobes and facultative anaerobes
Acquired: enzymatic destruction
Tetracyclines
Broad spectrum, safe to use, frequent cross resistance
Batceriostatic
Tetracyclines MOA
Prevents aa tRNA binding that blocks protein synthesis
Mammalian protein synthesis inhibited @ high concentrations
Tetracyclines PK
90-100% and broad for doxycycline (GI and eye)
Absorption ↓ by food
Wide distribution to body fluids and tissue, not CNS
Tetracycline binds to ________
Calcium
Tetracycline therapeutic uses
Broad spectrum G+ and G- aerobes and anaerobes
Rickettsia, chlamydia, ehrlichia and mycoplasma (doxycycline)
Anaplasmosis: oxytetracycline
______ are growth promotors in cattle and swine
Tetracyclines (in certain countries)
Tetracyclines adverse effects
Brown discoloration of the teeth
Doxycycline: nausea, vomiting, esophageal erosin in cats
Disruption of ruminal flora
Collapse with IV prep (cardio depression)
Tetracylines mechanism of resistance
Efflux pumps: ↓ accumulation via plasmid-bone transporter that pumps the drug out of bacteria
↓ binding to ribos
Enzymatic inactivation
Phenicols PK
Good oral absorptions
Inhibits microsomal enzymes
Phenicols MOA
Binds irreversibly to 50S ribosomal subunit and blocks peptidyl transferase → inhibits tranpeptidation and protein synthesis
Phenicols
Broad spectrum, obligate anaerobic
Eye, ear, mammary gland
Systemic infections caused by G- bacteria
__________ are an alternative to tetraclycines against rickettsia, chlamydia, ehrlichia
Phenicols
Chloramphenicol: ADR
Causes irreversible aplastic pancytopenia
Banned in food animals
Potent inhibitor of hepatic drug metabolizing enzymes
Florfenicol
Used for resp. diseases in cattle (shipping fever, infectious pododermatitis), swine (pasteurella, haemophilus, cornybacterium)
Clindamycin
Bacteriostatic, accumulation in WBC
Gram+ aerobes (Staph and strept), anaerobic, actinomycetes
Adverse drug events of clindamycin
Disruption of GI microflora (pseudomembranous enterocolitis, horses)
Macrolides
Broad, excellent Gram +, lipid soluble, acid labile drugs
Macrolide drugs
Erythromycin, azithromycin
Tylosin and Tilmicosin for animal use only
Macrolides MOA
Accumulates G+ 100 fold compared to G-
Blocks the transfer of growing polypeptide from the A site to the P
Tilmicosin uses
Bovine resp. disease (single treatment)
Tilmicosin adverse effects
Lethal to swine, goats, rabbits and humans
GI: fatal to horses
Where is tilmicosin prohibited in
Dairy cattle, veal calves
Streptogramines
Similar action as erythromycin with prolonged postabx affect
G+ cocci and vancomycin-resistant Enterococcus faecium
Adverse effects of streptogramines
Inhibits CYP3A4
Tiamulin
Growth promotor in swine
Used against swine dysentery and pneumonia, porcine colonic spirochaetosis, porcine proliferative enteropathy, leptospirosis, mycoplasmosis in cattle
Oxazolidinone (linezolid)
Bacteriostatic that interferes with 50s subunit and 23S ribosomal RNA
G+ and vancomycin resistant enterococcus faecium
Advers: thrombocytopenia
Streptinomycin
Bacteriostatic
Gram- infections
Feed additives daily 3-5 days
Resistance develops rapidly
