HYPNOTICS-SEDATIVES

DR. SUSHMA GHADIGAONKAR

ASSISTANT PROFESSOR
BOMBAY VETERINARY COLLEGE
 SEDATIVE

 A drug that decrease activity, moderate excitement

produce drowsiness and calm the animal.

 Wide variety of drugs –depress the function of CNS

 Term nonspecific

 Sedative & hypnotic no analgesic property but dull

perception of pain sensation
 HYPNOTIC

 A drug that induces and maintains sleep, similar to normal

arousal sleep.
 Hypnotic (from Greek Hypnos, sleep) or soporific drugs,
commonly known as sleeping pills
 a class of psychoactive drugs
 primary function is to induce sleep and to be used in the
treatment of insomnia (sleeplessness), or surgical
anesthesia.
 Higher doses-deep sleep and anaesthesia
 HYPNOTICS-SEDATIVES

 Also called sedative-hypnotics

 Generally produce a more profound degree of sedation
with greater drowsiness
 Depress CNS in dose dependent manner
 Produce sleep, unconsciousness, surgical anesthesia and
fatal depression of respiration and cardiovascular
regulation at high doses.
 Lab studies Hypnotics-Sedatives block both conditioned
and unconditioned reflex
 USES

 To facilitate handling and transport

 Modify behavior of animals
 Preanaesthetic medication
 Facilitate minor surgery
 Diagnostic procedure
 CLASSIFICATION OF SEDATIVES & HYPNOTICS

Nature of the chemicals

1. Benzodiazepines: e.g. diazepam, midazolam
2. Alpha 2 Adrenoreceptor agonists: e.g. Xylazine,
Detomidine, Medetomidine, Romifidine.
3. Barbiturates: e.g. Barbitone, Phenobarbitone,
Amobarbitone, Secobarbitone, Pentobarbitone.
4. Choral derivatives: e.g. Chloral hydrate
5. Aldehydes e.g. Paraldehyde
6. Inorganic salts e.g. Sodium bromide, Pot bromide,
Magnesium sulphate
7. Miscellaneous agents: a. Alcohols e.g. Ethyl alcohol
b. Piperinediones e.g. Glutethimide
 DIAZEPAM
 Most commonly used benzodiazepines in vet practice
 Representative of this class
 Affinity for plastic, may absorb –s/not stored in it

Pharmacological effects :
1. Sedation-hypnosis:
 Decreases time taken for sleep increases duration of sleep

 Preanaesthetic doses suppress excitatory and hallucinatory

effects
 Weak sedative in dogs
 PHARMACOLOGICAL EFFECTS
 Reduction of anxiety & aggressiveness: increases
locomotors feeding or drinking behavior.
 Muscle relaxant by central action
 Anticonvulsant
 Analgesia IV
 Respiratory system: high dose slightly depress ventilation
causes respiratory acidosis.
 CVS- Preanaesthetic doses decrease BP, increases HR
 Digestive system:
 Decreases gastric secretion, prevents stress ulcers in man
 Not affect GI motility.
 PHARMACOKINETIC
 Oral complete & rapid absorbed
 0.5-2hrs peak plasma protein, distributed in milk
 High lipid solubility, widely distributed, crosses BBB.
 Plasma protein binding 87%
 Metabolism in liver, active metabolites nordiazepam,
oxazepam
 diazepam nordiazepam oxazepam
glucuronide conjugate urine
 Active metabolites prolong duration of action
 Metabolites conjugate with glucuronide, excrete in urine
 Repeated administration- accumulation of nordiazepam
& other metabolites –cumulative effect
SIDE EFFECTS CONTRAINDICATIONS

 Horses: muscle  hypersensitive patient

fasciculation , ataxia  Severe hepatic damage,
recumbency due to sk nursing mothers
muscle relaxation.  Greyhound s/not
 Cats : irritability, hyperesthesia CNS
depression excitation
 Dogs: excitement  first trimester of
 Physical dependence in pregnancy-congenital
human abnormalities working
 withdrawal symptoms animals-impair working
after prolong use- anxiety, potential due to sedation
tremors, loss of appetite and drowsiness
DRUG INTERACTIONS CLINICAL USES
 Other CNS depressant  Hypnotic sedative muscle
 Cimetidine , relaxant anxiolytics ,
ketoconazole, appetite stimulant and
Propranolol, valproic anticonvulsive
acid erythromycin-  Restraining aggressive
decrease metabolism of animal
diazepam  Highly useful in epilepsy.
 Rifamycin induce hepatic
metabolism decrease
effect of diazepam
 XYLAZINE

 First Alpha 2 Adrenoreceptor agonists used as sedative

and analgesic in veterinary medicine.
 At present widely used in dogs, cats n horses
 Prototype this class
 Mechanism of action
 MECHANISM OF ACTION

 Stimulation of α2 adrenoceptor in brain.

 α2 adrenergic & opioid receptors found in same region of
brain.
 Both receptors connected to same signal transducers
 Both type of agonist used Same effector mechanism
 Xylazine binds with receptors –activation of membrane
associated G protein-opens K+ channels –
hyperpolarization.
 Cell unresponsive to excitatory unit
 Transmission pathway blocked
 Sedation and analgesia
 PHARMACOLOGICAL EFFECTS
 CNS: sedation, analgesia, muscle relaxation
anxiolytics .
 CVS: depression of vasomotor centre in brain stem-
increases central vagal and baroreceptors activity.
 Produce brief period of hypertension followed by
longer lasting decrease cardiac output and BP
 Respiratory system: relaxation of larynx and
suppress cough reflex
 Digestive system: acute abdominal distension in
large dogs , GI atony relaxation of smooth muscles
& decrease gastric secretions
 Hyperglycemia, polyuria.
PHARMACOKINETIC
 Rapid absorption but to variable extents
 Bioavailability 40-48 in Horses& 50-90% in dogs.

 Complete recovery 2-4 hrs in dogs, cats.

Side effects
 Vomiting cardiac arrhythmia bradycardia, reduce
RR, polyuria, transient hyperglycemia, sweating,
muscle tremors, premature parturition in cattle
 CNS and respiratory depression
CONTRAINDICATIONS AND USES
 Mechanical obstruction of GI tract in dogs, cats
 Later stages of pregnancy
 Concurrent administration of adrenoceptor
stimulant
 Pre-existing cardiac dysfunctions,
 severe renal /hepatic insufficiency , pre-existing
seizure disorders.
 Horses –an animal appear deeply sedated can still
kick in response to stimuli.
 person administering b’coz it absorbed through
mm and cuts in skins
CLINICAL USES
 Sedative in dogs, horses and cats.
 Preanesthetic sedative prior inhalant/injectable
anesthesia
 GA with Ketamine
 Sole agent for minor diagnostic & manipulation
procedures.
 Emetics to induce vomiting after ingesting toxins
 growth hormone stimulation test

* ruminants extremely sensitive compare to horses

requires 1/10th dose & s/not repeat if response not
seen
 DETOMIDINE
 Alpha 2 adrenoreceptor agonists
 Primarily synthesised for horses
 Pharmacological effect similar to Xylazine
 Dose dependent sedative and analgesic effects.
 More potent than Xylazine
 Well tolerated cardiac arrhythmia, sweating, ataxia,
piloerction, salivation, polyuria.
 contraindicated in preexisting heart, respiratory
disease.
 Approved for use of sedative in horses
 Animal should allow to rest quietly before & after inj
 MEDETOMIDINE
 Newest Alpha 2 adrenoreceptor agonists for veterinary.
 Structurally related to Xylazine & detomidine
 Similar pharmacological effects when use for dogs, cats
 Predictable sedation, analgesia in swine
 More potent than other
 Adverse similar to Xylazine
 As sedative in healthy exercised tolerant dogs over 12wk age
 Preanesthetic sedative prior to GA or local
 Sole agent for diagnostic and manipulation procedures
 Combined with opioid to produce sedation, analgesia.
ROMIFIDINE

 Alpha 2 adrenoreceptor agonists used as sedation

& preanesthetic medication in horses

 Animals sedated with romifidine can be made

walk, making it useful for loading, transportation
and turning out animals that have been stabled for
a period.
 BARBITURATES
 Barbiturates were widely used hypnotic sedative in
the past but now better drugs largely replace them.
 Barbiturates have been popular hypnotics and
sedatives of the last century upto 1960s but are not
preferred now.
 However, they are described first as they are the
prototype of CNS depressants.
 Several limitations
 lack of specificity,
 low therapeutic index,
 tolerance,
 drug interactions
 BARBITONE
 First barbiturate clinically used for CNS depressant

 Long acting barbiturate provide prolong sedation

 Basically used as hypnotic sedative , not as

anesthetics b’coz easily paralyses vital medullary
centers.

 Presently Barbitone sod clinically used

 150-1000mg Po once daily

 PHENOBARBITONE
 Long acting barbiturates
 Sedative hypnotics and anticonvulsive effects
 For sedative hypnosis primarily by oral and less IV
 Low partition coefficient hence penetrate BBB
slowly
 Excreted slowly, it has tendency to be cumulative
 Potent inducer of microsomal enzymes in liver
hence show drug interaction with no. of drugs
 Occasionally as general sedative in nervous &
irritable dogs
 2mg/kg PO 2to 3times daily.
CHLORAL HYDRATE

 Oldest sedative still used occasionally in large animals

 depresses cerebral cortex resulting in hyporeflexia
 IV or oral route –sedative effect.
 Oral-stomach tube b’coz it has pungent odour and
taste and animal do not take it .
 Produces sedation within 15min last 30-60min
 As sedative and adjunct to surgical anesthesia in large
ani
 Useful in quietening horse for shoeing & other
procedures
 Induce basal anesthesia in horses, cattle , swine
PARALDEHYDE
 Condensation product of 3 molecules of acetaldehyde
in the form of cyclic ether.
 Volatile liquid, pungent smell & disagreeable burning
taste.
 Irritant and inflammable
 Potent sedative hypnotic with short duration
 Normal doses safe b’coz it depresses only cerebrum
not vital medullary centers
 No selective analgesic & anticonvulsant action
 Metabolism in liver to acetaldehyde then CO2
 Restricted in both medical & vet practices due to
adverse effects & availability of better agents
 PARALDEHYDE

 Due to its excretion in unchanged form in the

breath it may cause soreness of trachea and lungs
imparts pungent odour to breath.
 Use of old , oxidized paraldehyde may cause
corrosive poisoning due to formation of acetic
acid.
 IV administration hemoglobinuria

 Acidosis, liver and kidney damage in toxicity.

 BROMIDE
 Bromide ion depress both motor and sensory areas of
cerebral cortex
 Sedative does not relieve pain
 Sodium and potassium bromide salt used
 Calcium and aluminium bromide may be used
 Cumulative action low doses long period –poisoning
 Bromide ion replace chloride ions in the body
 Slow onset of action
 Rarely used sedative in vet
 Calm down agitated horses in long travelling or when
working in noisy areas
PHENOTHIAZINE DERIVATIVES

 Generally classified as Neuroleptic or

antipsychotics

 Wide central and peripheral action

 Acepromazine, chlorpromazine, Triflupromazine

and propionylpromazine