Pharmacologic Effects

Barbiturates and benzodiazepines share many pharmacologic actions (e.g., sedation, muscle relaxation, anticonvulsant activity, and hypnosis) because of their interaction with the GABA-chloride ionophore receptor complex. GABA (y[γ]aminobutyric acid) is an inhibitory amino acid neurotransmitter. Benzodiazepines appear to increase the frequency of opening of the GABA-activated chloride ion channel in nerve membranes; barbiturates enhance the binding of GABA to its receptor and increase the time that the same GABA-activated ion channel is open. Thus, barbiturates and benzodiazepines both facilitate GABA-mediated inhibitory effects on the CNS.

The sedative and anxiolytic effects of the benzodiazepines are produced by doses that also produce muscle relaxation. The most commonly used benzodiazepine is diazepam. As with other drugs, there is great species variability in its effects. The effects in dogs, cats, and horses (Muir et al., 1982) are not the anxiolytic effects noted in people. Excitement, tremors, ataxia, dysphasia, and sometimes sedation occur in animals. There is no known explanation for the major species differences noted in response to the benzodiazepines in people and animals.

Dose Recommendations

Diazepam, usually administered intravenously, is painful if given intramuscularly. In rats, it is used as an anxiolytic at 1 mg/kg to lessen stress-induced increases in blood pressure, but not changes in heart rate (Conahan and Vogel, 1986). It can be used in ruminants for sedation at 0.2–0.5 mg/kg. In small ruminants, it is used as a premedication before ketamine anesthesia.

Diazepam and midazolam are usually used with other drugs in animals. The water solubility of midazolam, as opposed to the water insolubility of diazepam (compounded with propylene glycol), might be advantageous in some drug combinations, and midazolam is less irritating to tissues. However, it is more expensive. Tables 5-4 and 5-5 list combinations of diazepam with ketamine for surgical anesthesia in several species. The preanesthetic administration of the benzodiazepines with ketamine provides good muscle relaxation and eliminates tremors produced by ketamine.

α2-ADRENERGIC AGONISTS

Common Examples

Xylazine (Rompun®) and detomidine (Dormosedan®).

Clinical Uses

Xylazine is often used alone or with ketamine as a sedative and preanesthetic in ruminants and horses (Clarke and Hall, 1969; Hoffman, 1974; Klein and Baetjer,



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