Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
Differences in activity between different members of the
group are generally minor and are primarily due to
pharmacokinetic factors rather than differences in
susceptibility.
Clinical applications
● In veterinary medicine tetracyclines are used most
frequently for atypical bacterial diseases due to Chlamydophila
(particularly in cats), Borrelia, Rickettsia
and Mycoplasma.
● Tetracyclines are the drugs of choice for Ehrlichia
canis and Rickettsia rickettsii infections.
● Brucellosis is commonly treated with tetracyclines in
combination with rifampicin or streptomycin.
● Tetracyclines are used to treat bacterial overgrowth
of the small intestine and antibiotic-responsive diarrhea
(other common drug choices are tylosin and
metronidazole; this appears to be based on the clinician’s
preference rather than empirical data).
● Tetracyclines have anti-inflammatory properties
that are independent of their antibacterial
action, particularly in the case of doxycycline and
minocycline.
Pharmacokinetics
All tetracyclines are absorbed following oral dosing,
although absorption may be erratic – oxytetracycline
has the worst absorption, doxycycline and minocycline
the best. The drug’s ability to chelate calcium and other
divalent cations correlates with bioavailability. Systemic
availability after oral administration is impaired by
food, dairy products and antacids containing aluminum,
magnesium and calcium.
Tetracyclines vary in lipid solubility and this largely
determines their distribution and rate of excretion (see
Table 8.1). They enter most tissues and body fluids with
the exception of CSF; the degree to which they enter the
CNS and CSF is related to their lipid solubility and
presence of efflux pumps. Minocycline and doxycycline
are more lipid soluble than other tetracyclines but are
also more highly protein bound.
Tetracylines, except minocycline and doxycycline, are
excreted unchanged in urine. All are concentrated in the
liver and undergo biliary excretion and enterohepatic
recycling (which prolongs half-lives to 6–10 h and provides
some rationale for using them in bacterial cholangitis),
although the major route of elimination, except
for minocycline and doxycycline, is renal. Doxycycline
elimination in humans involves both renal and biliary
mechanisms but in dogs bile may be the predominant
route.
Preparations used in small animals include oral preparations
(capsules, syrup, paste), injectable preparations
and ophthalmic ointment.
Adverse effects
● Gastrointestinal disturbances are not uncommon,
especially in cats. Other adverse effects in cats can
include anorexia, fever and depression.
● Esophageal strictures resulting from incomplete swallowing
of oral doxycycline tablets have been reported.
As a precaution it is recommended that animals be
given a small amount of water by syringe or a small
amount of food following administration, or butter
be placed on the nose to encourage swallowing.
● Tetracyclines are irritant and may cause vomiting
after oral administration and tissue damage at injection
sites. This is particularly true for oxytetracycline,
especially long-acting preparations.
● Fatal anaphylaxis has occasionally been recorded.
● Rapid IV injection is likely to cause the patient to
collapse (probably related to the vehicle).
● Tetracyclines have been reported to induce doserelated
functional changes in renal tubules in several
species. This may be exacerbated by dehydration,
hemoglobinuria, myoglobinuria, toxemia or another
nephrotoxic drug.
● Severe renal tubular damage has been attributed to
the administration of outdated or incorrectly stored
preparations.
● Severe liver damage has been reported following
overdosage of tetracyclines in animals with preexisting
renal failure.
● Fatal nephrotoxicosis has been reported after accidental
administration of two doses of 130 mg/kg.
● Superinfection is a risk with most tetracyclines
because appreciable amounts remain unabsorbed in
the bowel and they are actively excreted into bile.
This is especially true in the horse where the lipophilic
tetracyclines minocycline and doxycycline
have such a high potential for causing digestive disturbances
that they should be avoided.
● Serious adverse effects have been reported in hamsters
and guinea-pigs but tetracyclines appear to be
safe for rabbits.
● Tetracyclines may accumulate in renal failure and
their antianabolic effect could exacerbate azotemia
in renal failure, so dosage should be modified in
patients with renal failure. The exception is doxycycline,
the elimination of which is not affected. Doxycycline
is therefore the tetracycline of choice for
patients with renal disease.
● The antianabolic effects of tetracyclines may
cause azotemia, potentially exacerbated by
corticosteroids.
● Tetracyclines chelate with calcium pyrophosphate in
teeth and bone. This causes hypoplasia of dental
enamel, discoloration of developing teeth and slower
bone development. This may not occur with
doxycycline.
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