Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHLORAMPHENICOL
● Tetracyclines should not be used in pregnant animals
because of their antianabolic effects.
CHLORAMPHENICOL
Originally isolated from Streptomyces venezuelae,
chloramphenicol was the first broad-spectrum antibacterial
developed (1947). It is now produced
synthetically.
Mechanism of action
Chloramphenicol is a nonionized, highly lipophilic compound.
It enters bacterial cells by passive or facilitated
diffusion and binds primarily to the 50S ribosomal
subunit but may also bind to the 30S subunit. As a result
bacterial protein synthesis is inhibited.
Chloramphenicol can also bind to the mammalian
ribosome (70S) that resembles bacterial ribosomes and
interfere with mitochondrial protein synthesis. This is
particularly relevant in erythropoietic cells.
Resistance
Resistance is commonly plasmid-mediated and occurs
as a result of enzymatic inactivation by several types of
chloramphenicol transacetylase.
Antibacterial spectrum (Fig. 8.16)
● Chloramphenicol is bacteriostatic for most Grampositive
and many Gram-negative aerobic bacteria
but can be bactericidal against some very sensitive
bacteria.
● Acquired resistance occurs in many species, especially
where chloramphenicol is in common use.
Pseudomonas aeruginosa, Escherichia, Klebsiella,
Enterobacter, Salmonella and Proteus now show
patterns of plasmid-mediated resistance. However,
the current level of acquired resistance is difficult to
predict, as chloramphenicol is not used in food
animals in many countries and is now used much less
frequently than previously in small animals.
Gram positive
aerobes
Obligate
anaerobes
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus
+ Chlamydophila, Rickettsia are susceptible
Fig. 8.16 Antibacterial spectrum for chloramphenicol.
● All anaerobic bacteria are inhibited by chloramphenicol
at usual therapeutic concentrations.
● Chloramphenicol suppresses growth of Rickettsia
and Chlamyophila but clinical efficacy against Mycoplasma
infections is often disappointing, even though
Mycoplasma often seem susceptible in vitro.
● Mycobacterium and Nocardia are resistant.
Clinical applications
● In many countries, use of chloramphenicol in any
form, including topical and ophthalmic preparations,
is prohibited in food-producing animals. This is
because chloramphenicol, even in minute doses, is
associated with an idiosyncratic fatal aplastic anemia
in some humans.
● In small animals, chloramphenicol is often regarded
now as the drug of first choice only for bacterial
infection of the chambers of the eye.
● There is mixed opinion as to whether chloramphenicol
is a drug of choice for bacterial CNS infections
but it does achieve high levels in the CNS and has a
very broad spectrum. However, many other drugs
also effectively cross the blood–brain barrier in the
presence of meningitis and may be more effective
and, perhaps most importantly, are bactericidal.
● Chloramphenicol may be indicated for anaerobic
infections, prostatitis and salmonellosis.
● As chloramphenicol is usually bacteriostatic, it
should not be used in immunocompromised patients
or where bactericidal treatment is preferable.
● Chloramphenicol is best avoided in anemic
animals.
● Avoid using chloramphenicol in cats with renal
failure.
Pharmacokinetics
● Well distributed throughout the body, including
CNS and eye.
● Attains higher concentrations in CSF than other antibacterials
(30–50% of plasma concentrations in the
absence of meningitis) and concentrations in CNS
are maintained longer than in plasma.
● Eliminated primarily by hepatic glucuronide conjugation
in the dog: only 5–10% is excreted unchanged
in the urine.
● In the cat, more than 25% is excreted in the urine
because of reduced ability to glucuronidate drugs.
● Elimination half-life is similar in both species: 4 h
following IV administration, 7–8 h following PO
administration.
● Drug from tablets and capsules is readily absorbed
orally.
● In fasted cats chloramphenicol suspensions (palmitate
ester) administered PO produce lower blood
drug concentrations than provided by solid dosage
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