SEDATIVES (No Drugs)

Sedatives

CNS-acting drugs that ↓ activity and excitement, produce calmness, and may cause drowsiness

Main veterinary uses of sedatives

Restraint, handling, transport, pre-anesthetic medication, minor diagnostic/surgical procedures, behavior modification, and sedation of animals requiring monitoring

Hypnotic-sedatives

Sedatives that produce sedation at lower/normal doses and hypnosis at higher doses

Hypnosis

An artificial state of deep sleep or trance in which the animal is not entirely unconscious and can be aroused by sensory stimulation

Hypnotic-sedatives at high doses

May produce sleep, deep sleep, unconsciousness, anesthesia, and respiratory depression

Tranquilizer-sedatives

Sedatives that primarily produce tranquilization and lower drowsiness compared with hypnotic-sedatives

Benzodiazepine MOA

Act as positive allosteric modulators of GABA-A receptors, enhancing GABA-mediated inhibition

Benzodiazepine binding site

A site on the GABA-A receptor that is different from the GABA binding site

Benzodiazepine effect on chloride channels

Increase the frequency of Cl⁻ channel opening when GABA is present

Benzodiazepines and GABA

Enhance the effect of GABA but do not replace GABA or effectively activate GABA-A receptors without GABA

Benzodiazepine cellular effect

↑ Cl⁻ influx → neuronal hyperpolarization → ↓ neuronal firing

Benzodiazepine effects

Sedation, anxiolysis, muscle relaxation, and anticonvulsant effect

Benzodiazepine antidote

Flumazenil

α₂-adrenoceptor agonist MOA

Stimulate α₂ receptors → ↓ norepinephrine release → CNS depression

α₂-adrenoceptor agonist effects

Sedation, analgesia, muscle relaxation, and CNS depression

Ruminant response to α₂-adrenoceptor agonists

Ruminants are very sensitive, particularly to xylazine, and require much lower doses

Barbiturate MOA

Bind to GABA-A receptors and enhance GABA-mediated inhibition

Barbiturate effect on chloride channels

Increase the duration of Cl⁻ channel opening

Barbiturate cellular effect

↑ Cl⁻ influx → hyperpolarization → ↓ neuronal excitability → ↓ CNS activity

Barbiturate effects

Sedation, hypnosis, anesthesia, and anticonvulsant effect

Benzodiazepines vs barbiturates

Benzodiazepines ↑ frequency of Cl⁻ channel opening, whereas barbiturates ↑ duration of Cl⁻ channel opening

Barbiturate therapeutic index

Low therapeutic index, so overdose may be lethal

Barbiturate toxicity treatment

There is no specific pharmaceutical antidote

Phenothiazine MOA

Mainly block dopamine receptors, especially D₂ receptors, in the CNS

Phenothiazine CNS effect

↓ dopaminergic stimulation → ↓ CNS arousal and behavioral response → tranquilization and sedation

Phenothiazine α₁ antagonism

Causes vasodilation and may produce mild to moderate hypotension

Phenothiazine H₁ antagonism

Contributes to calming, anti-nausea, and anti-allergic effects

Phenothiazine muscarinic antagonism

Produces mild anticholinergic effects, including dry mouth and urinary retention

Phenothiazine 5-HT₂ antagonism

Contributes to anti-anxiety and anti-aggressive effects

Phenothiazines and analgesia

Phenothiazines provide no analgesic effect

Phenothiazine effects

Tranquilization, sedation, antiemetic effect, decreased response to conditioned stimuli, and decreased spontaneous motor activity

Phenothiazine adverse effects

Hypotension, possible hypothermia, nictitating membrane protrusion, and possible penile prolapse in male horses

Butyrophenone MOA

Competitive antagonists of central dopaminergic D₂ receptors

Butyrophenone adverse effects

QT prolongation and torsades de pointes

Neuroleptanalgesia

A state produced by combining a neuroleptic/tranquilizer with an opioid analgesic, producing profound sedation with analgesia

Hypnotic-sedatives vs tranquilizer-sedatives — drowsiness

Hypnotic-sedatives produce high drowsiness, whereas tranquilizer-sedatives produce low drowsiness

Hypnotic-sedatives vs tranquilizer-sedatives — high dose

Hypnotic-sedatives may cause deep sleep, unconsciousness, anesthesia, and respiratory depression, whereas tranquilizer-sedatives may cause cataleptic immobility with minimal respiratory depression and retained consciousness

Hypnotic-sedatives vs tranquilizer-sedatives — conditioned reflexes

Both groups can block conditioned reflexes

Hypnotic-sedatives vs tranquilizer-sedatives — unconditioned reflexes

Hypnotic-sedatives block both conditioned and unconditioned reflexes, while tranquilizer-sedatives generally do not block unconditioned reflexes