Benzodiazepines: Choosing the right drug (Proceedings)

Animal Medicinal Drug Use Clarification Act (AMDUCA 1994)

Valid client/veterinarian/patient relationship

Behavioral history MUST be taken

Veterinarian has established a diagnosis and the need for treatment

Must be a specific rationale, and its use is accepted under current medical conditions.

Extra-label usage

Inform client of the extra-label status of the drug.

Inform the client of known side-effects.

Signed informed consent statement.

Psychoactive medications are usually most effective when used as an adjunct to behavior modification and environmental management. It is rare for a pill to provide a "cure".

Some psychoactive drugs have potential for human abuse, especially the benzodiazepines.

Action: Facilitates GABA in the CNS by binding to GABAA receptors.

DEA Class IV

Rapid onset of action

Lasts only a few hours

All are metabolized by the liver and excreted through the kidneys

Pregnant or lactating females?

Excreted in milk

Passes through placenta

Wide usage in phobias and anxiety-related problems

     Noise phobias (e.g. thunderphobia)

     Submissive urination

     Fear of people or animals, without aggression

     Fear of objects

     Separation anxiety

     Fear of going outside

Combination?

Can be safely used with many other medications, including TCA's, SSRI's and MAOI's

General issues to consider

Cost

Forms available in

     Tablets

     Capsules

     Liquids

Sizes available in

Side-effects

General issues to consider

Duration of action varies with

     Species

     Specific benzodiazepine

     Concurrent use of other medications which may compete with or interfere with metabolic pathway

     Concurrent illness, especially kidney or liver

     Intensity of stress exposed to

Side Effects:

     Sedation

     Muscle relaxation

     Increased appetite

     Paradoxical excitation

     Idiopathic hepatic necrosis in cats.

Timing

Can give several times a day, as needed

If fear inducing event is predictable, give 30-60 minutes prior to event

Special circumstances

Use minimum or below minimum dose in patients that are

     Old

     Obese

     Have compromised liver function

     Have compromised kidney function

May interfere with learning conditioned responses

However research evidence is contradictory.

Effect on learning varies with

     Specific drug

     Species given to

     Specific dose

     Single or repeat dosing

Use with caution in fear aggression. Learned inhibition of aggression may be lost.

Effect on aggression varies with

     Specific drug

     Species given to

     Specific dose

     Single or repeat dosing

Use in aggression

Do not use as first drug of choice in cases of aggression

Fear aggression

     Inadequate response to treatments that do not include benzodiazepine

     Fear is clearly a significant issue that is interfering with the patient's and family's ability to make progress

Try a benzodiazepine, after discussing the potential problem with owners and making appropriate safety arrangements for first 2-3 doses

     Muzzle?

     Baby-gate?

Tolerance

A patient may respond well to a given dose but gradually require increasing doses of medication to attain the same level of efficacy.

Discontinuing

Withdraw gradually

Possible physical addiction if has been on daily for several weeks.

Sudden termination in a patient that has been on for a long period of time can result in rebound, i.e. a resumption of symptoms which may be more intense than prior to treatment. In case of overdose:

Overdose

Overdose must be very large to be life-threatening

Most healthy pets will tolerate a fairly high dose and simply sleep

Flumazenil (Mazicon) benzodiazepine receptor antagonist

Muscle relaxation vs. Lethal dose: mg/kg in Cats

Individual response

If the patient does not respond as desired, or has undesirable side-effects, with one benzodiazepine, a different benzodiazepine may be effective and appropriate

Alprazolam→Diazepam

Diazepam→Alprazolam

Client: Potential for human abuse

Potential for human abuse; carefully monitor dose size and number for non-human patients

Psychological dependency

Physical dependency

Ideally

     Begin when situation for which drug is being used does not exist, e.g. owner home and no storms.

     Test lowest dose to make sure animal is not unusually sensitive (ataxic, sedated) and does not show paradoxical excitement.

Test in actual situation, e.g. thunderstorm, owner leaves (videotape)

If sufficient, maintain that dose

If insufficient, incrementally increase the dose

When discontinuing, rule of thumb is to decrease dose by 25% each week

Extended release forms?

Designed for human digestive tract

Alprazolam (Xanax & generic)

     DOGS: 0.02-0.1 mg/kg q3-4h

     CATS: 0.125-0.25 mg/cat q12h

     Available in 0.25, 0.5, 1.0 and 2.0 mg tablets

     Used for panic disorder in humans

     Rapid onset of good panic efficacy in most dogs

     Inexpensive

Clonazepam (Klonopin and generic)

     DOGS: 0.1-0.5 mg/kg q6h

     CATS: 0.015-0.25 mg/cat q12h

     Available in 0.25, 0.5, 1.0 and 2.0 mg tablets

Clorazepate (Tranxene & generic)

     DOGS: 0.5-2.0 mg/kg q12h

     CATS: 0.5-2.0 mg/kg q12h

     Available in 3.75, 7.5, 11.25, 15.0 and 22.5 mg tablets and 3.75, 7.5 and 15.0 mg capsules

Longer duration of action than most benzodiazepines

Expensive

Diazepam (Valium & generic)

     DOGS: 0.5-2 mg/kg q 6-24h

     CATS: 1.25-2.5 mg/cat q12h

Inexpensive

Idiopathic hepatic necrosis

Ingredient in medication?

     Several brands caused death

Idiosyncratic reaction?

Pre-existing disease?

Virus?

Oxazepam (Serax)

     Dogs: 0.04-0.5 mg/kg q6h

     Cats: 0.2-1.0 mg/kg q12h

     Available as 10, 15 and 30 mg capsules and as 15 and 30 mg tablets

     Difficulty dosing small animals

     No active intermediate metabolites

     May be safer than other benzodiazepines for patients with liver disease, obese patients and geriatric patients