Protein Synthesis Inhibitors (ribosomes Flashcards by Trenni Jefferson

Aminoglycosides

Gram- aerobes (pseudomonas, best drug)
Selected gram + aerobes (staph)
Combination therapy (with B-L)
Nocardia and atypical mycobacteria

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Aminoglycosides structure- activity relationship

Weak base
Oxygen dependent
Resistance to obligate anaerobes

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Aminoglycosides PK

Initiation of protein synthesis (bactericidal)
Concentration dependent (10x MIC)
Long post abx effect (once daily dosing)

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How does pH affect aminoglycosides

Alkaline pH → enhanced efficacy
Acidic pH → trapped → ↓ oral absorption, milk and enhances renal toxicity

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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)

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Aminoglycosides adverse effects

Toxicity dose related
Acute tubular nephrosis
Risk based on # of amines (+ charges)
Toxicity for cochlea and vestibular apparatus

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Aminoglycoside neurologic effect

Neuromuscular paralysis (antagonized with neostigme or calcium)
Interferers with calcium flux and ACh release

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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

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Aminoglycosides compliance

ELDU discouraged but not prohibited

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Approved aminoglycosides for food animals

Apramycin
Gram - infections
Pig and calves 28 day withdrawal

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Gentamicin

Broad-spectrum, used with B-L, synergistic effects
Used for infections requiring aminoglycosides

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Amikacin

Intrauterine for horses
Broad spectrum effective against ESBL producing E. coli

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What is Amikacin used for?

Infections caused by E. coli, Klebsiella, pneumoniae and other multi-drug resistance bacteria

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Apramycin use

In pigs for colibacilosis (pig scours)

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Neomycin

Mostly topical or oral use
Local effect in the intestine
Treats enteritis caused by E. coli

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Aminoglycosides resistance

Inherent: Obligate anaerobes and facultative anaerobes
Acquired: enzymatic destruction

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Tetracyclines

Broad spectrum, safe to use, frequent cross resistance
Batceriostatic

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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