Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

TETRACYCLINES
● Little resistance 10 years ago but resistant strains
are emerging, particularly in some referral centers.
These are mainly detected in dogs with oft-treated
ear infections.
● Gentamicin has little activity against
Mycobacterium.
Tobramycin
● Very similar antibacterial spectrum to gentamicin;
some cross-resistance occurs but is unpredictable.
● More active against Pseudomonas.
Amikacin
● Amikacin is resistant to most enzymes that inactivate
other aminoglycosides, particularly important in
treating serious Pseudomonas and other Gramnegative
infections in immunosuppressed patients.
● Can be administered for 2–3 weeks at recommended
doses with less risk of nephrotoxicity than with
gentamicin.
Spectinomycin
Is an aminocyclitol rather than an aminoglycoside but
has many similar properties.
● Lacks most of the toxic effects of the
aminoglycosides.
● Is usually bacteriostatic but may be bactericidal at
higher concentrations (e.g. 4 × MIC).
● Has limited clinical application because resistance
develops readily.
● Is marketed in combination with lincomycin, which
marginally enhances activity against Mycoplasma.
TETRACYCLINES
The tetracycline group of drugs were first developed in
the late 1940s.
EXAMPLES
Chlortetracycline, doxycycline, minocycline, oxytetracycline,
tetracycline.
Mechanism of action
Like the aminoglycosides, tetracyclines inhibit protein
synthesis by binding to the 30S subunit of bacterial
ribosome and interfering with RNA-protein translation.
Access to ribosomes is by:
● passive diffusion through hydrophilic pores in the
outer cell membrane
● energy-dependent active transport through the inner
cytoplasmic membrane. This involves a periplasmic
protein carrier. Unlike aminoglycosides, this step
does not depend on membrane potential; therefore
tetracyclines can work in anaerobic and hyperosmolar
environments.
Tetracyclines also bind to mammalian 80S ribosomal
subunits and inhibit protein synthesis in the host but
with much less affinity. However, host protein synthesis
in rapidly dividing cells may be impaired at high doses,
resulting in an antianabolic effect. Selective toxicity is
dependent on mammalian cells lacking the transporter
molecule so they do not accumulate the drug in the same
way that bacterial cells do.
Mechanism of resistance
Acquired resistance to tetracyclines is widespread,
usually plasmid-mediated, and often involves interference
with both active transport of tetracyclines into, and
increased efflux out of, bacterial cells. Another major
mechanism is ribosomal protection where a cytoplasmic
protein protects against inhibition of protein synthesis.
At least 12 different genetic determinants for tetracycline
resistance have been described, coding for several
mechanisms of drug resistance such as efflux, ribosomal
protection or chemical modification.
Antibacterial spectrum (Fig. 8.15)
● Tetracyclines have activity against many Grampositive
and Gram-negative aerobic bacteria but
acquired resistance limits their activity against many
species, such as Staphylococcus, Enterococcus,
Enterobacteriaceae including Enterobacter, Escherichia,
Klebsiella, Proteus and Salmonella.
● Mycobacterium, Proteus vulgaris, Pseudomonas
aeruginosa and Serratia are resistant.
● Anaerobes show variable susceptibility.
● Atypical bacterial species (Rickettsia, Borrelia,
Chlamydophila and Mycoplasma) are generally
susceptible, though some Mycoplasma (M. bovis, M.
hyopneumoniae) are resistant.
Gram positive
aerobes
Obligate
anaerobes
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus
+ many atypical bacteria – Mycoplasma, Chlamydophila,
Rickettsia, Borrelia – are susceptible
Fig. 8.15 Antibacterial spectrum for tetracyclines.
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