Sedative Tranquilizers

Sedative Tranquilizers

On the basis of the type of effect produced, two general classes of sedative can be distinguished.

I.  Tranquilizer Sedative / Neuroleptics / Ataractics

1.       Phenothiazines – Promethazine, Acepromazine, Promazine, Chlorpromazine

2.       Butyrophenones – Azaperone, Droperidol

3.       Rauwolfia alkaloids – Reserpine

II. Classical sedative / Sedative hypnotics

1.       Barbiturates – Phenobarbitone

2.       α ₂ adrenergic agonist – Xylazine, detomedine, Medetomidine

3.       Benzodiazepines – Diazepam, Chlordiazepoxide, Clonazepam

Pharmacological actions

·         They exert calming, quieting effects on animals, reduce locomotor activity and induce indifference to the surroundings.

·         Classical sedatives produce more drowsiness than sedative tranquilizers.

Pharmacological properties	Tranquilizer sedatives	Sedative Hypnotics
Arousal reaction on sensory stimulation	Depressed	Normal or even exaggerated
Dose response relationship	Predictable and steep	Less predictable and flat
Effects of high dose rate	Loss of consciousness, anaesthesia, respiratory depression	Consciousness retained and the animal remains in the state of cataleptic immobility. Minimal respiratory depression.
Effect of emesis	No effect or central stimulant action (except Xylazine)	Depression of chemoreceptor trigger zone(CTZ)  in medulla
Anticonvulsant action	General for most drugs (Diazepam and Phenobarbitone used clinically)	More limited and not used clinically
Analgesic action	Absent or poor. But definite analgesia with α 2 agonist	Generally absent
Premedication for anaesthesia	Duration not affected. Suppression of recovery / excitement may be limited.	Prolong anaesthesia and suppress recovery excitement.
Cardiovascular system	Generally mild vasodepression  (except Xylazine – transient hypertension and bradiarrhythmia)	Vasodepression and reduction of vasomotor tone
Effect on autacoids	No specific antagonistic action, but Xylazine suppress the symptoms of acute inflammation	Most drugs possess antagonistic actions against histamine and 5- hydroxytryptamine.
Safety Margin	Generally wide	Very wide and lower in hypovolumic animals.

I.  Tranquilizer Sedative / Neuroleptics / Ataractics

Phenothiazines

·         One of the most potent Phenothiazine is acepromazine

·         While used clinically give fewer problems than other phenothiazines and more potent than promazine

·         For these reasons it has accepted as the first choice phenothiazine for veterinary use.

·         They block dopamine, α₁ adrenergic and serotonergic receptors.

·         Does not produce analgesia

·         CVS – Hypotension , Bradicardia and reflex tachycardia

·         Respiration – Minimal respiratory depression

·         GI tract – Motility inhibited and emesis suppressed.

Clinical Uses

·         For restraining of animals.

·         Promethazine – to control allergy

·         Their application as premedication in cattle is limited, since they tend to prolong the periods of anaesthesia and recumbency. Potential problems of ruminal engorgement (leading to bloat) and respiratory complications may be exacerbated.

Adverse effects

·         Paraphimosis may occur in stallions – so it should be used cautiously or avoided in breeding stallions.

·         Inhibit cholinesterase and may worsen the clinical signs of anticholinesterase poisoning.

·         No reversal agent for this class of drugs.

·         Accidental intracarotid administration – immediate seizure and death in horse

Butyrophenones

·         Only three butyrophenones have been used to a significant degree in veterinary medicine and two of these are droperidol and fluanisone. These two drugs are generally available only as combination products with narcotic-analgesics, Fentanyl as neuroleptanalgesia.

·         Third is azaperone used extensively in pigs and it is probably the sedative of choice in pigs and to a much lesser degree in horse.

·         They block dopamine, α₁ adrenergic and serotonergic receptors.

·         At equieffective dose rate, butyrophenones generally possess fewer side effects than phenothiazine.

Rauwolfia alkaloids

·         Reserpine, an alkaloid derived from the plant, Rawolfia serpentine, was once used in man for its antihypertensive effects and antipsychotic properties.

·         It decreases binding of catecholamines and 5-hydroxytryptamine to their storage granules and thus causes depletion.

·         Duration of action is long and the safety margin is narrow.

·         It is no longer used clinically as a sedative.

·         Behavioral change has been detected in the horse for up to several weeks after reserpine administration. It’s illegal use is therefore favored  Eg: show horses

II. Classical sedative / Sedative hypnotics

α ₂ adrenergic agonist

·         Activate α ₂ receptor that is a presynaptic G-protein coupled receptor.

·         It has powerful analgesic action.

·         Induce potent sedation. Degree of sedation varies among species.

·         Ruminants are more sensitive followed by cats, dogs and horse.  Pigs are least sensitive and not commonly used in them.

·         It relaxes smooth muscles by inhibiting intraneuronal transmission of impulse in CNS (not in neuromuscular region)

·         Induces emesis in carnivores and omnivores and is common in cat and less frequently in dog.

·         Reduces GI motility and secretions.

·         CVS:  Mild hypertension for ≤ 10 minutes followed by hypotension lasting for several hours. May result in bradicardia and second degree heart block.

·         Induce diuresis by inhibiting vasopressin release.

·         Cause hypoxemia in ruminants especially in sheep and is not seen in other species.

Clinical use

·         Sedative

·         Analgesic

·         Immobilizing agent

·         Preanaesthetic medicament

·         As a part of anaesthetic combination.

Reversing agent - α 2 antagonist

·         Yohimbine (Non ruminants), Tolazoline (Ruminants), Atipamizole (All species)

Xylazine

·         Xylazine plus ketamine combination should be used only in young healthy animals because this combination synergistically suppresses cardiopulmonary function of the animal.

·         Xylazine should not be given to animals (particularly in mares and ruminants) in last month of pregnancy, since it may induce abortion.

·         Should not be given to dehydrated animals or animals those with urinary obstruction because of its potent diuretic effect.

Contraindications

·         Cardiac aberrations, Hypotension / Shock, Renal insufficiency, Hepatic impairment and Epilepsy.

Detomidine

·         Approved by FAO for use in horse

Medetomidine

·         Most potent and selective drug available for use in veterinary medicine

·         As it is very potent, adverse effects may be very severe.

Romitidine

·         For intravenous administration in horse.

Benzodiazepines

·         It acts by facilitating GABA action

·         Minimal cardiovascular effects

·         Dose dependant respiratory depression noticed.

·         Skeletal muscle relaxation, by inhibitory effects on spinal cord.

·         Administered with ketamine or tiletamine to provide smooth muscle relaxation.

·         Diazepam – used along with butorphanol as neuroleptanalgesia

                                       Also used along with ketamine

·         Midazolam- Used along with butorphanol and ketamine

·         Zolazepam – Used along with Tiletamine

·         Reversal agent – Flumazenil

Barbiturates

·         It was widely used as sedative-hypnotic in the past, but now better drugs have largely replaced them.

Phenobarbitone

·         For sedative and hypnotic purpose given orally.

·         Used occasionally for a general sedative effect in nervous and irritable dog.

·         May be indicated in dogs suffering from pruritus to depress the itching sensation that results in scratching or even biting with considerable damage to the skin.