Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

AMITRIPTYLINE HCL

Chemistry - A tricyclic dibenzocycloheptene-derivative antidepressant, amitriptyline HCl occurs asa white or practically white, odorless or practically odorless crystalline powder that is freely solublein water or alcohol. It has a bitter, burning taste and a pKa of 9.4.

Storage, Stability, Compatibility

Amitriptyline tablets should be stored at room temperature.
The injection should be kept from freezing and protected from light.

Pharmacology - AMITRIPTYLINE HCL

Amitriptyline (and its active metabolite, nortriptyline) has a complicated pharmacologic profile. From a slightly oversimplified viewpoint, it has 3 main characteristics: blockageof the amine pump, thereby increasing neurotransmitter levels (principally serotonin, but alsonorepinephrine), sedation, and central and peripheral anticholinergic activity. In animals, tricyclicantidepressants are similar to the actions of phenothiazines in altering avoidance behaviors.

Uses, Indications

Amitriptyline has been used for separation anxiety in dogs, and excessivegrooming, spraying and anxiety in cats.

Pharmacokinetics - AMITRIPTYLINE HCL

Amitriptyline is rapidly absorbed from both the GI tract and from parenteralinjection sites. Peak levels occur within 2-12 hours. Amitriptyline is highly bound to plasmaproteins, enters the CNS, and enters maternal milk in levels at or greater than that found in maternalserum. The drug is metabolized in the liver to several metabolites, including nortriptyline, which isactive. In humans the terminal half life is approximately 30 hours. Half life in dogs has beenreported to be 6-8 hours.

Contraindications, Precautions, Reproductive Safety

These agents are contraindicated if priorsensitivity has been noted with any other tricyclic. Concomitant use with monoamine oxidaseinhibitors is generally contraindicated. Isolated reports of limb reduction abnormalities have beennoted; restrict use to pregnant animals only when the benefits clearly outweigh the risks.

Adverse Effects, Warnings

The most predominant adverse effects seen with the tricyclics arerelated to their sedating and anticholinergic properties. Occasionally, dogs exhibit hyperexcitability.
However, adverse effects can run the entire gamut of systems, including hematologic effects (bonemarrow suppression), GI effects (diarrhea, vomiting), endocrine effects, etc. Refer to otherreferences for additional information.
Overdosage, Acute Toxicity - Overdosage with tricyclics can be life-threatening (arrhythmias, cardiorespiratory collapse). Because the toxicities and therapies for treatment are complicated andcontroversial, it is recommended to contact a poison control center for further information in anypotential overdose situation.

Drug Interactions

Because of additive effects, use amitriptyline cautiously with other agents withanticholinergic or CNS depressant effects. Tricyclic antidepressants used with antithyroidagents may increase the potential risk of agranulocytosis. Cimetidine may inhibit tricyclic antidepressant metabolism and increase the risk of toxicity. Use in combination with sympathomimetic agents may increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia). Concomitant use with monoamine oxidase inhibitors is generally contraindicated.
Laboratory Considerations - Tricyclics can widen QRS complexes, prolong PR intervals andinvert or flatten T-waves on ECG. The response to metapyrone may be decreased by amitriptyline.
Tricyclics may alter (increase or decrease) blood glucose levels.

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