Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 7 BEHAVIOR-MODIFYING DRUGS
Adverse effects
It should be noted that, because clomipramine is registered
for use in animals, more is known about its specific
effects in companion animals than those of other
TCAs. However, the pharmacology of other TCAs
in companion animals is expected to be similar to
clomipramine.
● The most predictable side effects are short-term lethargy
or sedation, mild and intermittent vomiting
which is usually transient and increases or decreases
in appetite.
● Anticholinergic side effects may be encountered,
often, but not always, at high dose rates.
● Other side effects, which usually disappear if the
dose is decreased or the medication is withdrawn,
include:
– Sedation (antihistamine effect)
– Dry mouth (antimuscarinic effect)
– Constipation (antimuscarinic effect)
– Tachycardia
– Cardiac arrhythmias
– Ataxia
– Decreased tear production
– Mydriasis
– Disturbances of accommodation.
● High doses have been associated with increased liver
enzymes, hepatotoxicity and convulsions.
● A few cases of urine retention have been reported
in cats after treatment with clomipramine. This
effect is likely to be the result of decreased
bladder muscle tone, which decreases intraluminal
pressure and allows collapse of the trigone area,
obstructing urinary outflow. Hence animals treated
with clomipramine should be monitored daily for
signs of urine retention or constipation. If urine
retention or constipation occurs, drug administration
should be stopped until normal urination or
defecation is observed, then reinstated at a lower
dose.
● Cats are more sensitive to the cardiac effects of
TCAs than dogs and should be monitored closely.
● In humans, TCAs may lower the seizure
threshold.
● TCAs should be used with caution in patients with
hyperthyroidism or receiving thyroid supplementation
as there may be an increased risk of cardiac
arrhythmias.
Contraindications and precautions
● Cardiac dysrhythmias
● Urinary retention
● Concurrent use of hypertensive drugs
● Narrow angle glaucoma
● Seizures
Known drug interactions
● Concurrent MAOI administration should be avoided
as it may lead to a serotonin syndrome.
● TCAs used with antithyroid medications may increase
the potential risk of agranulocytosis.
● As TCAs are strongly bound to plasma protein, their
effects may be temporarily enhanced by drugs that
compete for protein-binding sites (e.g. aspirin,
phenylbutazone).
● As hepatic metabolism is necessary for elimination,
drugs such as neuroleptics and some steroids may
inhibit metabolism.
● Simultaneous administration of clomipramine and
cimetidine (an enzyme inhibitor) may lead to
increased plasma levels of clomipramine.
● Plasma levels of certain antiepileptic drugs such as
phenytoin and carbamazepine may be increased by
coadministration with clomipramine.
● Clomipramine may potentiate the effects of antiarrhythmic
drugs, anticholinergic agents and other
CNS-acting drugs (e.g. barbiturates, benzodiazepines,
neuroleptics).
● Concurrent use with sympathomimetic drugs may
increase the risk of cardiac effects (arrhythmias,
hypertension).
Selective serotonin reuptake inhibitors
Currently, there are at least five selective serotonin reuptake
inhibitors (SSRIs) on the market worldwide for
human use. As their collective name implies, they are
selective for serotonin, lacking the anticholinergic and
cardiovascular side effects of TCAs. They do not resemble
TCAs structurally and have minimal autonomic
activity. They have much improved safety and tolerability
over the TCAs and MAOIs and wider therapeutic
indications than depression.
EXAMPLES
Fluoxetine (Prozac®), paroxetine, sertraline, fluvoxamine,
citalopram.
Clinical applications
Apart from the treatment of depression, SSRIs have
been used successfully in cases of panic disorder, obsessive-compulsive
disorder, posttraumatic stress disorder,
chronic pain, social phobias, enuresis and eating disorders
in humans.
In cats, fluoxetine and paroxetine have been used to
treat urine spraying, with the reported success rate of
fluoxetine being around 80% for urine spraying and
anxiety-related disorders. Both have also been used to
treat some types of aggression and obsessive-compulsive
disorders.
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