Diazepam

Diazepam: Uses, Dosage and Side Effects

Overview

Enhances the activity of the major inhibitory central nervous system neurotransmitter, gamma-aminobutyric acid (GABA), through binding to the benzodiazepine site of the GABAA receptor.

Uses of Diazepam

• Anticonvulsant: diazepam is the drug of choice for the short-term emergency control of severe epileptic seizures and status epilepticus in dogs and cats.
• Anxiolytic: used in behavioral medicine for anxiety and fear-related disorders in dogs and cats, especially where there are signs of panic.
• Skeletal muscle relaxant (e.g. urethral muscle spasm and tetanus).
• Used in cats as an appetite stimulant.

Dose of Diazepam in Dogs and Cats

Dogs:

• Anxiolytic: 0.5–2.0 mg/kg p.o as required.
• Sedation and premedication: 0.2–0.5 mg/kg i.v., i.m.
• Skeletal muscle relaxation: 2–10 mg/dog p.o. q8–12h.
• Emergency management of seizures, including status epilepticus: bolus dose of 0.5–1 mg/kg i.v. or intrarectally. Time to onset of clinical effect is 2–3 min for i.v. use; therefore, repeat every 10 min if no clinical effect, up to 3 times. Additional doses may be administered if appropriate supportive care facilities are available (for support of respiration).
• Constant rate i.v. infusion for control of status epilepticus or cluster seizures:
  initial rate 0.5–2 mg/kg/h, titrated to effect.

Cats:

• Anxiolytic: 0.2–0.4 mg/kg p.o. q8h.
• Appetite stimulant: 0.1–0.2 mg/kg i.v. once.
• Behavioral modification of urine spraying and muscle relaxation: 1.25–5 mg/cat p.o. q8h.
• The dose should be gradually increased to achieve the desired effect without
  concurrent sedation.
• Emergency management of seizures including status epilepticus:
• A bolus dose of 0.5–1 mg/kg i.v. or intrarectally if venous access is not available.
• Time to onset of clinical effect is 2–3 min for i.v. use, therefore, repeat every 10 min if there is no clinical effect, up to a maximum of 3 times.
• Constant rate i.v. infusion for the control of status epilepticus or cluster seizures: initial rate of 0.5 mg/ kg/h.
• Care should be taken in cats to avoid overdosing; if cats demonstrate excessive sedation then diazepam should be discontinued.
• Consider monitoring liver parameters.

Side Effects of Diazepam in Dogs and Cats

• Ataxia, sedation, and lethargy are common.
• Slow i.v. injections (at least 1 min per 5 mg) can prevent paradoxical excitation (including hostility) and pain in normal dogs.
• Intramuscular injection hurts and disrupts drug uptake.
• If i.v. access is unavailable, rectal administration can manage seizures, but it takes 5–10 min to start.
• In older animals, those with liver dysfunction, and those getting beta-1 antagonists, repeated doses in rapid succession may prolong the duration of action.
• Repeated oral giving causes feline fulminant hepatic necrosis.
• Emulsion diazepam is favored for intravenous injection because propylene glycol can cause thrombophlebitis.

Contraindications of Diazepam in Dogs and Cats

• Patients with CNS depression, respiratory depression, severe muscle
  weakness, or hepatic impairment (as may worsen hepatic encephalopathy).
• long-term treatment of canine and feline behavioral disorders due to the risks of disinhibition and interference with memory and learning.

Some Notes:

• Do not dilute or mix with other agents.
• Due to extensive metabolism by the hepatic microsomal enzyme system,
  interactions with other drugs metabolized in this way are common.
• Cimetidine and omeprazole inhibit the metabolism of diazepam and may prolong clearance.
• Concurrent use of phenobarbital may lead to a decrease in the half-life of diazepam.
• An enhanced sedative effect may be seen if antihistamines or opioid analgesics are
  administered with diazepam, and diazepam will reduce the dose requirement of other anesthetic agents.
• When given with diazepam the effects of digoxin may be increased.
• Diazepam may be used in combination with tricyclic antidepressant therapy for the
  management of more severe behavioral responses