Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

PURE VASODILATORS
nitroglycerin, including dosing, are anecdotal. Nitroglycerin
is most commonly administered in conjunction
with furosemide, usually to patients with severe heart
failure. Beneficial effects in this situation cannot be
directly ascribed to nitroglycerin because it is well
known that furosemide by itself can produce dramatically
beneficial effects in these patients.
In our clinic, transdermal nitroglycerin is only rarely
used in patients with heart failure. However, we have
on occasion observed beneficial effects in dogs that were
not responding or had become unresponsive to other
cardiovascular drugs. Consequently, there may be a
limited role for this drug in veterinary patients. Nitroglycerin
is not a very effective drug and should never be
administered as the sole agent to a patient with moderate
to severe heart failure.
Formulations and dose rates
Nitroglycerin ointment is available in a 2% formulation to be spread
on the skin for absorption into the systemic circulation. Numerous
manufacturers also supply it in a transcutaneous patch preparation.
Nitroglycerin is diluted with lactose, dextrose, alcohol, propylene
glycol or another suitable inert excipient so that the medical-grade
material usually contains about 10% nitroglycerin. It appears as a
white powder when diluted with lactose or as a clear, colorless or
pale yellow liquid when diluted with alcohol or propylene glycol.
Nitroglycerin is also supplied as a liquid for intravenous administration.
Extended-release preparations are supplied as capsules or
scored tablets.
In dogs and cats, 2% nitroglycerin cream has been used (12 mm
per 2.5 kg bodyweight q.12 h for dogs, 3–6 mm q.4–6 h for cats) but
effi cacy has not been documented. If transcutaneous nitroglycerin
cream is used, it should be applied on a hairless area (usually inside
the ear fl ap), using gloves, since transcutaneous absorption will occur
in the clinician or owner as well as in the patient. Cutaneous absorption
in a human can cause a profound headache and a very unhappy
client. Transdermal patches have been used successfully in large
dogs with dilated cardiomyopathy.
When nitroglycerin is administered intravenously it acts as a potent
arteriolar dilator and venodilator. The onset of action after intravenous
administration is similar to nitroprusside. Duration of effect is minutes
so the drug must be administered by CRI. The recommended administration
rate to start with in humans is 5 µg/min. This dose is
increased in increments of 10–20 µg/min until an effect is identifi ed.
There is no fi xed optimum dose. Effective doses in small animals have
not been identifi ed. To use this drug, a low starting dose would have
to be identifi ed and titrated upward as blood pressure was
monitored.
In cats and dogs, extended-release nitroglycerin can be used to
treat refractory heart failure alone or in conjunction with other vasodilators.
Most experience has been garnered in dogs and cats with
refractory ascites or pleural effusion. Anecdotal evidence would
suggest that the time between fl uid removal can be increased by
several weeks if extended-release nitrogylcerin is used and in some
cases use of the drug may eliminate the need for fl uid removal alto-
gether. The dose should be titrated, starting at 2.5 mg q.12 h orally
in cats up to a maximum of 6.5 mg q.8 h PO. Small dogs can be
treated the same as cats. In medium to large dogs, the dose is started
at 6.5 mg q.12 h PO. The maximum dose is 9.0 mg q.8 h PO.
Mechanism of action
Nitroglycerin is an organic nitrovasodilator that possesses
a nitrate ester bond. The biotransformation of
nitroglycerin to nitric oxide is complex and not completely
understood. Thiols (compounds containing sulfhydryl
groups) appear to be important as intermediary
structures.
Pharmacokinetics
Nitrates are metabolized in the liver by nitrate reductase
to two active major metabolites: 1,2- and 1,3-dinitroglycerols.
Although less active than their parent compounds,
they may be responsible for some of the
pharmacological effect.
Nitroglycerin has a very short half-life of 1–4 min. It
is metabolized to 1,3-glyceryl dinitrate, 1,2-glyceryl
dinitrate and glyceryl mononitrate. The parent compound
is approximately 10–14 times as potent as the
dinitrate metabolites but the metabolites have longer
half-lives and are present in substantial plasma concentrations.
The mononitrate metabolite is inactive. The
onset of action with the transdermal route of administration
is delayed and the duration of effect is prolonged.
Transdermal systems are designed to provide continuous,
controlled release of nitroglycerin to the skin, from
which the drug undergoes absorption. The rates of delivery
and absorption of the drug to the skin vary with the
specific preparation. Individual manufacturers’ information
for a drug should be consulted for this information.
However, one must remember that this information pertains
to human skin and probably does not translate into
the actual rate of delivery for a dog or a cat.
Special considerations
Nitroglycerin ointment should be stored in airtight containers
at 15–30°C. Owners should be instructed to
close the container tightly immediately after each use.
Intravenous nitroglycerin solutions should be stored
only in glass bottles because nitroglycerin migrates
readily into many plastics. About 40–80% of the total
amount of nitroglycerin in a diluted solution for IV
administration is absorbed by the polyvinyl chloride
(PVC) tubing of IV administration sets. Special non-
PVC-containing administration sets are available.
Isosorbide mononitrate and dinitrate
Clinical applications
Isosorbide mononitrate and dinitrate are organic nitrates
that can be administered orally, primarily to patients
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