Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
Teicoplanin
● Teicoplanin is administered IM but can also be
given by rapid IV injection.
Adverse effects
● Toxicity information is only available for humans.
● Nephrotoxicity and otoxicity are potential but
uncommon with vancomycin. They are rare with
teicoplanin and usually only occur in patients also
receiving an aminoglycoside.
● Skin rashes and hypersensitivity reactions have been
reported with both drugs in humans.
● Reversible neutropenia has been reported in humans
treated with vancomycin especially if given at high
doses for prolonged periods.
● PO administration of vancomycin may cause nausea
and inappetence.
Bacitracin
Bacitracin inhibits the formation of bacterial cell wall
peptidoglycan by complexing directly with the pyrophosphate
carrier and inhibiting the dephosphorylation
required for its regeneration. Bacitracin has activity
against Gram-positive organisms but causes nephrotoxicity
if given systemically and so is restricted to topical
and ophthalmic use in combination with polymyxin
and/or neomycin.
ANTIBACTERIALS ACTING BY INHIBITING
CELL MEMBRANE FUNCTION
The cytoplasmic membrane of certain bacteria (and fungi)
can be more readily disrupted by certain agents than the
cell membranes in animals. Therefore selective chemotherapeutic
activity is possible, even though the drugs
involved have a narrow therapeutic index. These antibacterials
induce chemical instability in cell membranes,
altering their permeability and causing cells to lose their
osmotic integrity. This is similar to a detergent action.
Examples of agents acting in this manner are polymyxins
and certain antifungal agents (amphotericin
B, imidazoles, triazoles). The latter are discussed in
Chapter 9.
Polymyxins
Mechanism of action and resistance
Polymyxins (including colistin, or polymyxin E) are cationic,
surface-active agents that disrupt the structure of
cell membrane phospholipids and increase cell permeability
by a detergent-like action. Gram-negative bacteria
are much more sensitive than Gram-positive bacteria
because they contain more phospholipid in their cytoplasm
and outer membranes. Acquired resistance is rare
but can occur with Pseudomonas aeruginosa as a result
of decreased bacterial permeability.
Antibacterial spectrum
Polymyxins are highly active against many Gramnegative
bacteria, including Pseudomonas aeruginosa
but not Proteus. Activity against P. aeruginosa is reduced
in vivo by calcium at physiological concentrations.
Clinical applications
Although polymyxins can be given parenterally, the
incidence of serious nephro- and neurotoxicity is such
that they are only indicated in small animal medicine
when other effective, nontoxic drugs are not available.
Therefore they are generally only used in topical or
ophthalmic medications, often in combination with
bacitracin and neomycin or tetracycline.
ANTIMICROBIALS AFFECTING
BACTERIAL PROTEIN SYNTHESIS
AMINOGLYCOSIDES AND
AMINOCYCLITOLS
EXAMPLES
Aminoglycosides: amikacin, framycetin (in ocular and aural
preparations only), gentamicin, kanamycin, neomycin,
streptomycin, tobramycin
Aminocyclitols: spectinomycin
Members of this group continue to be important for
treating serious Gram-negative infections. All inhibit
bacterial protein synthesis and suffer the disadvantage
of multiple types of resistance and several potential side
effects.
Mechanism of action
Aminoglycosides cause irreversible inhibition of bacterial
protein synthesis, although the exact mechanism for
this is unknown. The agent must penetrate the cell envelope
to exert its effect; this happens partly as an active
process and partly by passive diffusion. Penetration of
the cell envelope can be enhanced by drugs that interfere
with cell wall synthesis, such as penicillins. Because
active transport is an oxygen-dependent process, aminoglycosides
are inactive against anaerobes and against
facultative anaerobes growing under anaerobic conditions,
as in abscesses.
Aminoglycosides bind to receptors on the 30S subunit
of bacterial ribosomes and induce misreading of the
genetic code on the messenger RNA template. This
results in incorporation of incorrect amino acids into
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