Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 19 GASTROINTESTINAL DRUGS
Formulations and dose rates
Sulfasalazine is available as tablets or liquid. Various dosage regimens
have been successfully used.
DOGS
• Some clinicians recommend a dose of 10–15 mg/kg PO q.8–
12 h for 2 weeks, then tapered to the lowest effective dose
• Other reports suggest that higher doses are required, e.g. 20–
50 mg/kg (up to a maximum of 1 g) PO q.8 h; from 2–4 weeks,
attempts can be made to taper the dose gradually (e.g. by
reducing 25–50% of the dose every 2–4 weeks) to the lowest
effective dose
• Therefore, it is usually recommended to start at a low dose
(e.g. 12.5 mg/kg PO q.8 h) and increase this after 4 weeks if it
has been ineffective
• Olsalazine is used in dogs that cannot tolerate sulfasalazine.
The recommended dose is 10–20 mg/kg PO q.8 h
CATS
• 10–20 mg/kg PO q.24 h. The reduced dosing interval is used in
light of increased sensitivity to salicylates in this species
Pharmacokinetics
After oral administration approximately 20–30% of the
drug is absorbed in the small intestine. Some of this
absorbed drug is believed to be excreted unchanged into
the bile. Unabsorbed and biliary excreted drug is cleaved
in the colon by bacterial flora. Because the colonic
microflora is required to cleave the drug, sulfasalazine
is not effective against small bowel inflammation. The
sulfapyridine component is rapidly absorbed but only a
small percentage of the 5-ASA is absorbed; both are
metabolized in the liver and excreted in the urine.
Olsalazine is poorly absorbed and that which is absorbed
is rapidly eliminated. Approximately 98% of an oral
dose is thought to reach the colon.
Adverse effects
● The major adverse effect, although uncommon, is
keratoconjunctivitis sicca. Should decreased tear
production be recorded, this can be resolved by
reducing the dose or discontinuing the drug
altogether.
● Other occasional adverse effects include vomiting,
allergic dermatitis, cholestatic jaundice, hemolytic
anemia and leukopenia.
● Drug hypersensitivity manifested as lethargy, pyrexia,
arthralgia and cutaneous drug eruption can occur
with sulfonamide drugs and has been reported with
the use of sulfasalazine.
Known drug interactions
● Sulfasalazine may displace other highly proteinbound
drugs such as methotrexate, warfarin,
phenylbutazone, thiazide diuretics, salicylates and
phenytoin. The clinical significance of these interactions
has not been established.
● Sulfasalazine may decrease the bioavailability of
folic acid or digoxin. Antacids may decrease the
oral bioavailability of sulfasalzine if administered
concurrently.
● Antacids may decrease the oral bioavailability of
sulfasalazine if administered concurrently.
● As with other sulfonamides, sulfasalazine may affect
blood thyroid concentrations, e.g. decreased total
and free T4, increased cTSH.
● Olsalazine may causes increases in plasma concentrations
of ALT and AST.
APPETITE STIMULANTS
The main appetite stimulants used in companion animals
are the H 1 -receptor antagonists cyproheptadine and
diazepam. In both drugs, the appetite stimulation is
effectively a ‘side effect’ of the indication for which they
were predominantly designed.
Cyproheptadine also has serotonin antagonist and
calcium channel-blocking properties. It is indicated for
short-term use as an appetite stimulant in cats; profound
anorexia or chronic nutritional disorders are
better managed with more intensive nutritional support,
i.e. tube feeding. The drug is well absorbed, almost
completely metabolized in the liver and metabolites are
excreted in the urine. The main side effects are sedation
and anticholinergic effects (dry mucous membranes,
mydriasis); occasional reports of hemolytic anemia have
been described.
Diazepam is used mainly for its anticonvulsant, anxiolytic
and skeletal muscle relaxant properties. However,
when used IV, it can be an effective appetite stimulant
in cats. Again, only short-term (and preferably single)
use is recommended. The IV preparation should be
injected slowly, since rapid administration may cause
marked excitation. Thrombophlebitis has also been
reported. The drug should be used with caution in
patients with pre-existing or suspected renal or hepatic
insufficiency. The main side effects include muscle fasciculations,
weakness, ataxia, behavior changes and
excessive sedation. Fulminant hepatic necrosis has also
been described in cats after oral administration (usually
for >5 d). Given that the IV preparation is used for
appetite stimulation, the significance of this finding is
unclear. Nevertheless, cautious use is recommended.
CATS
Cyproheptadine
• 1–4 mg per cat PO q.12–24 h
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