Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
forms (this difference is not observable in dogs).
Since many sick cats given chloramphenicol are inappetent,
tablets rather than suspension should be
given.
● Parenteral formulations are sodium succinate solution
(which has an excellent bioavailability regardless
of route) and aqueous suspension (gives lower
plasma concentrations, maximum concentration 6 h
after injection). Parenteral routes are only used in
patients for whom oral dosing is impossible.
● Chloramphenicol should not be given to young
animals (ill-equipped with metabolizing enzymes)
and avoided in adults with liver disease.
Adverse effects
● Reversible, dose-related nonregenerative anemia can
occur in dogs and cats. Cats may be more susceptible
but the increased prevalence is probably related to
overdosing of cats if using the dog dosing schedule,
which is approximately five times higher per kilogram
(see Table 8.4).
● Idiosyncratic fatal aplastic anemia has not been
reported in small animals.
● Chloramphenicol inhibits hepatic microsomal
enzymes, thus prolonging effects of drugs such as
barbiturates and phenytoin. The inhibition is irreversible
and therefore long lasting.
● Chloramphenicol may also theoretically interfere
with antibody production in active immunization
procedures.
Related drugs
Thiamphenicol is a chloramphenicol analog with a
range of activity similar to chloramphenicol, although
it is generally 1–2 times less active. It has equal activity
against Haemophilus, Bacteroides fragilis and Streptococcus.
It differs pharmacokinetically in that it is not
eliminated by hepatic glucuronidation and is excreted
unchanged in urine, so elimination is unaffected by liver
disease. Unlike chloramphenicol, thiamphenicol does
not cause aplastic anemia in humans.
Florfenicol is a structural analog of thiamphenicol
which has greater in vitro activity against pathogenic
bacteria than chloramphenicol and thiamphenicol. It is
also active against some bacteria that are resistant to
chloramphenicol, especially enteric bacteria. Florfenicol
is not susceptible to inactivation by chloramphenicol
transacetylases; thus some organisms that are resistant
to chloramphenicol through this mechanism are susceptible
to florfenicol.
In dogs florfenicol is poorly absorbed after SC administration.
It has a half-life of less than 5 h. The drug is
well absorbed in cats after PO and IM administrations
with a similar elimination half-life. It should not be
given IV. Florfenicol can cause dose-related bone
marrow suppression but has not been reported to cause
fatal aplastic anemia in humans.
Florfenicol shows promise as a replacement for other
broad-spectrum antibacterials such as sulfonamides and
tetracyclines that have been associated with toxicity and
residue concerns in food animals. Currently it is
approved for use only in cattle, aquaculture and pigs.
In cattle it is used to treat infectious conjunctivitis and
respiratory disease caused by bacteria like Pasteurella
and Haemophilus.
MACROLIDES AND LINCOSAMIDES
These groups of antibacterials are structurally distinct
but considered together because they have many
common properties.
EXAMPLES
Macrolides: azithromycin, clarithromycin, erythromycin,
spiramycin, tilmicosin, tulathromycin, tylosin.
Lincosamides: clindamycin, lincomycin.
Mechanism of action and resistance
The mechanism of action of the macrolides and lincosamides
is similar to that of chloramphenicol, acting on
the 50S ribosomal subunit. Chromosomal resistance
develops fairly readily to both these drug groups and
plasmid-mediated resistance is common.
Resistance is the result of methylation of adenine residues
in the 23S ribosomal RNA of the 50S ribosomal
subunit, which prevents drug binding to the target. There
is usually complete cross-resistance between lincomycin
and clindamycin and cross-resistance between lincosamides
and macrolides is common.
Antibacterial spectrum (Figs 8.17–8.20)
● Active against Gram-positive aerobic bacteria,
Mycoplasma and Bartonella henselae (cat scratch
disease).
Gram positive
aerobes
Obligate
anaerobes
* Campylobacter are susceptible
Gram negative
aerobes*
Penicillinaseproducing
Staphylococcus
Fig. 8.17 Antibacterial spectrum for lincomycin,
*Campylobacter spp. are susceptible.
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