Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 19 GASTROINTESTINAL DRUGS
Zinc
Zinc is a nutritional metal agent that is used to reduce
copper toxicity in breeds with copper-associated hepatopathies,
e.g. Bedlington terrier. It is also reported to
have antifibrotic functions. The effect of copper toxicosis
relates to the ability of zinc to inhibit the absorption of
copper in the gastrointestinal tract. For liver disease, zinc
supplementation is often provided as part of a purposeformulated
prescription diet. However, oral and injectable
forms are also available and usually include either
zinc acetate or zinc sulfate. Zinc acetate is the preparation
most commonly used for hepatic disorders.
Large doses of zinc can cause gastrointestinal signs,
including vomiting, whilst hemolysis can occur after
administration of large doses or if serum concentrations
exceed 1000 µg/dL. Penicillamine and ursodeoxycholic
acid can decrease zinc absorption, whilst zinc salts can
reduce the absorption of tetracycline and fluoroquinolones
(e.g. enrofloxacin). It is recommended to stagger
dosing by at least 2 h.
Formulations and dose rates
DOGS
Copper-associated hepatopathy
• 5–10 mg/kg (of elemental zinc) PO q.12 h. Start at the higher
end of the dose range for the fi rst 3 months, then reduce dose
to 50 mg PO q.12 h for maintenance. Separate the dose from
feeding by 1–2 h. Monitor plasma zinc concentrations every
2–3 months and aim for plasma zinc concentrations of
200–400 µg/dL
Hepatic fibrosis
• 10 mg/kg (of elemental zinc) q.24 h PO, aiming for plasma zinc
concentrations between 200–300 µg/dL
S-adenosyl methionine (SAMe)
S-adenosyl methionine (SAMe) is an endogenous molecule
which is synthesized, from methionine, by many
cells in the body. However, the enzyme SAMe synthetase
is found in the liver and is the rate-limiting step for
SAMe synthesis in the face of hepatic compromise.
SAMe is an essential factor in three major biochemical
pathways (most important in the liver), namely transmethylation,
transsulfuration and aminopropylation.
SAMe functions as a donor of methyl groups and is thus
essential for the activation or elimination of many
substances. For transsulfuration, SAMe generates
sulfur-containing compounds, which are important for
conjugation reactions and for synthesis of glutathione
(GSH). The latter is also essential for numerous metabolic
processes and detoxification reactions; conversion
of SAMe to GSH requires folate, cyanocobalamin and
pyroxidine. Ample SAMe is usually synthesized but,
with hepatic disease or if toxic substances are present,
conversion to GSH may be reduced. Administration of
exogenous SAMe increases hepatic and red blood cell
GSH concentrations, whilst this compound also inhibits
apoptosis secondary to the presence of alcohol or bile
acids in hepatocytes. Other effects include antidepressant
activity, possibly due to increased serotonin
turnover, and increased dopamine or noradrenaline
(norepinephrine) release.
Oral bioavailability is reported to be 1% and the
amount absorbed can be reduced further in the presence
of food. Once absorbed, SAMe enters the portal circulation
and is metabolized in the liver.
Clinical applications
SAMe is most frequently used as adjunctive therapy for
a variety of hepatic disorders (canine chronic hepatitis,
hepatic lipidosis, cholangiohepatitis, etc.). It may also
be beneficial in the treatment of certain hepatotoxic
disorders, most notably paracetamol (acetaminophen).
Formulations and dose rates
No pharmaceutical preparations exist; SAMe is considered to be a
nutritional supplement. Therefore, potency, purity, safety and effi cacy
may vary across the various preparations. Specifi c animal products
exist, e.g. Denosyl®, Zentonil® and Hepatosyl®.
DOGS AND CATS
• Calculate daily dose based upon 17–20 mg/kg PO q.24 h (or
divided twice daily), rounded to the closest tablet size. The
product should be administered on an empty stomach, ≥1 h
before feeding
• Or, dose according to the following regimen: 5.5 kg, 90 mg PO
q.24 h; 5.5–11 kg, 180 mg PO q.24 h; 11–16 kg, 225 mg PO
q.24 h; 16–29.5 kg, 450 mg PO q.24 h; 29.5–41 kg, 675 mg
PO q.24 h; 41 kg+, 900 mg PO q.24 h
Adverse effects
SAMe appears relatively safe for use in small animals
and adverse effects are minimal. In humans, oral dosing
may cause anorexia, nausea, vomiting, diarrhea, flatulence,
constipation, dry mouth, insomnia, headache,
sweating and dizziness.
Known drug interactions
Concurrent use of pethidine (meperidine), monoamine
oxidase inhibitors (e.g. selegiline), serotonin reuptake
inhibitors (e.g. fluoxetine) and other antidepressants
(e.g. amitryptiline, clomipramine) could cause additive
serotonergic effects.
Silymarin
Milk thistle, Silybum marianum, is a flower used for
thousands of years for medical purposes. Three bio-
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