START WITH THE NAME OF

ALLAH
THE BENEFICIENT,
THE MERCIFUL

1 September 29, 2018

 HYPNOTIC DRUGS

Prof. Dr. Muhammad Ashraf

Dean FBS
UVAS, Lahore

2 September 29, 2018

 HYPNOTIC DRUGS

3 September 29, 2018

 Hypnosis
 Greater depression of CNS
 Animal is asleep, can be awakened
STAGES OF CNS DEPRESSION

Awake Sedation Hypnosis Narcosis

Anesthesia Medulary paralysis Coma
Death

4 September 29, 2018

5 September 29, 2018
 Sedative Hypnotics
 These include 3 types of drugs;
 Benzodiazepines
 Barbiturates
 Miscellaneous agents

6 September 29, 2018

  Factors Affecting Anesthesia
 Blood Gas Solubility
 Potency
 Gas Lipid Solubility
 Blood Gas Solubility
 More the solubility of the inhalant anesthetic, it will take more time to saturate
and more time to depress the Brain and vice versa.
 So, more the solubility of an inhalant anesthetic, it will take more time for
induction and recovery of Anesthesia.
 Low solubility inhalant anesthetic
 Low the solubility of inhalant anesthetic, minor change in concentration will
lead to greater change in depth of anesthesia.
 Low solubility inhalant anesthetics include Nitrous oxide, Ether,
Halothene, Fluorine.

7 September 29, 2018

8 September 29, 2018
 DRUGS
 1. Benzodiazepines
 2. Barbiturates
 3. Miscellaneous agents (Non Barbiturates)

9 September 29, 2018

 Benzodiazepines
 Introduced in 1960.
 Sedative hypnotic depending on dose and compound.
 Minor tranquillizers.
 Most widely used in human less in veterinary practice.
 More effective and safe as compared to barbiturates
 They have high therapeutic index.

10 September 29, 2018

  Benzodiazepines (BZ)
 These were introduced in 1960.
 These are most commonly used.
 Mechanism of Action
 It is based on GABA receptors stimulation.
 GABA (amino acid) binds with receptors and chloride channels open and there is influx
of chloride ions which leads to hyper-polarization of membrane and sedation
occurs. This is normal phenomenon.
 Benzodiazepines facilitate this mechanism by facilitating the binding of GABA receptors
to their receptors which lead to sustained hyper-polarization.
 It is dose dependent effect;
 Low dose…. Sedation
 High dose… Hypnosis
 If GABA concentration is low, BZ are not able to perform their action because these only
facilitate binding not the release of GABA.

11 September 29, 2018

 Mechanism of Action

 Binds with benzodiazepine receptors.

 Enhances binding of GABA with its receptors
 Opens Cl ion channels.
 Increases Influx of Cl ions
 Causes hyperpolarization
 Inhibits formation of action potential
 Inhibition of neuronal firing

12 September 29, 2018

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 Classification
 Classification is based on duration of action.

< 5 hours)
 SHORT ACTING (t½

Midazolam …… Preanesthatic.
Triazolam ………Hypnotic, Preanesthatic.

15 September 29, 2018

 INTERMEDIATE ACTING (t½ 5-24 hours)
 Alprazolam…..Anxiolytic, Antidepressant
Panic disorders
 Clonazepam…Anticonvulsant
 Lorazepam ….Anxiolytic, Hypnotic,
Preanesthatic.
 Temazepam... Hypnotic.

16 September 29, 2018

  LONG ACTING (t½ > 24 hours)
 Diazepam (Valium) Anxiolytic,
Preanesthatic
Anticonvulsant
 Chlorodiazepoxide Anxiolytic,
Preanesthatic
 Flurazepam Hypnotic
 Quazepam Hypnotic

17 September 29, 2018

  Classification of BZ
 Their classification is based on duration of activity;
 Short Acting BZ
 Drugs with half life less than 5 hours and include;
 Midazolam
 Triazolam
 Medium Acting BZ
 Drugs with half life b/w 5-24 hours and include
 Alprazolam
 Lorazepam
 Long Acting BZ
 Drugs with half life greater than 24 hours and include
 Diazepam
 Chlorodiazep
 Flumazenil
 This drug is used to treat the toxicity of BZ b/c it is antagonist of BZ.

18 September 29, 2018

 Pharmacological effects
 Sedative, hypnotic
 Reduction of anxiety
 Anticonvulsant
 Muscle relaxant
 Effect on C.V. System (minor effect)
 Effect on respiration (slight effect)
 Analgesia (poor)

19 September 29, 2018

 Therapeutic uses
 Sedative hypnotic
 Anxiety disorders
 Muscle relaxant
 Sleep disorders
 Anticonvulsant
 Preanesthetic medication

20 September 29, 2018

 Dependence

 Develops if given high doses for long period.

 More pronounced with short acting benzodiazepines.
 Withdrawal symptoms include:

confusion Restlessness
Anxiety Insomnia
Agitation Tension

21 September 29, 2018

 Adverse Effects
Drowsiness and confusion

Antidote
Flumazenil

22 September 29, 2018

  Effects of BZ
 These act as anti-convulsants and also reduce the anxiety.
 These are poor analgesic but good muscle relaxant.
 Effects on CVS and respiratory systems are negligible.
 Therapeutic Uses
 Sedative and hypnotic
 Anti-convulsants
 Used for sleep disorders
 Pre-anesthetic
 Midazolam can be used as anesthetic agent.
 Problem
 If used for longer duration, problem of dependency occurs and abrupt
withdrawal leads to anxiety, convulsions and other withdrawal symptoms.

23 September 29, 2018

 Barbiturates
 Synthetic compounds
 Urea + Malonic acid Barbituric acid
 Thiourea + Malonic acid Thiobarbituric acid
 Sodium salt increases water solubility
 Thiol group increases lipid solubility
 Barbituric acid itself is not hypnotic
 Substitution at C5 yield compounds having hypnotic
properties

24 September 29, 2018

 Urea + Malonic acid

25 September 29, 2018

  barbituric acid:

26 September 29, 2018

  Barbiturates
 These are synthesized from urea and malonic acid.
 Urea and malonic acid combine to form Barbituric acid.
 Barbituric acid is not having hypnotic property.
 When hydrogen at 5th carbon in Barbituric acid is replaced by other substitutes, then
these have hypnotic property.
 If thiaurea is used instead of Urea, Thiobarbiturates are formed which are good
lipid soluble. Sodium salts of Thio-barbiturates are used as injectable anesthetics.
 These are having dose dependent effect;
 Low dose…Sedation
 High dose…Hypnosis
 Higher dose…..Anesthesia
 In BZ, higher dose do not lead to anesthesia.
 So Barbiturates are used as general anesthetics.

27 September 29, 2018

 Classification of Barbiturates
1. Ultrashort acting Barbiturates
- Use as I/V anaesthetic
- Duration 10 – 30 mins
Examples
- Thiopentone
- Hexobarbitone
2. Short duration Barbiturates
- Used as Hypnotics
- Effect less than 3 hrs.
Examples
- Pentobarbitone
- Secobarbitone
28 September 29, 2018
 3. Medium duration Barbiturates
- Duration of action is more than 3 hrs. but less than 6
hrs.
Examples
- Butobarbitone
- Amylobarbitone
4. Long acting Barbiturates
- Duration of action more than 6 hrs.
Examples
- Phenobarbitone
- Mephobarbitone
- Barbitone
29 September 29, 2018
  Classification of Barbiturates
 Their classification is also based on duration of activity;
 Ultra-short acting
 Drugs with half life b/w 10-30 minutes and include;
 Thiopental
 Thiobarbitone
 hexobarbitone
 Short acting
 Drugs with half life b/w 30min-3hours and include;
 Pentobarbitone
 Secobarbitone
 Medium acting
 Drugs with half life b/w 3-6 hours and include;
 Butobarbitone
 Amylobarbitone
 Long acting
 Drugs with half life more than 6 hours and include;
 Phenobarbitone
 Mephobarbitone

30 September 29, 2018

 Mechanism of action
 Depress all parts of CNS (Variable depression)
 Reduce neuronal excitability by increasing thresh hold
for excitation
 Enhance binding of GABA with its receptors
- Open Chloride channel
- Influex of Cl-
- Hyperpolarization

- Decreased excitability

31 September 29, 2018

 General Effects
 Hypnotic and anaesthetics effects
 Anticonvulsant effects
 Analgesic effects
 Respiratory effects
 Uterine effects

32 September 29, 2018

 Hypnotic & Anaesthetic Effects
a) Dose dependent CNS depression
b) Low doses Sedative and Hypnotic, induce
sleep which can be awakened at normal stimuli
c) High doses Anaesthesia. Animal cannot be
aroused
d) Anaesthetic doses Very close to lethal doses so
only ultra short acting barbiturates are used as minute
to minute adjustment is possible

33 September 29, 2018

 Anticonvulsant Effects
a. Abolish convulsions induced by drugs or disease such as
tetanus, eclampsia and epilepsy
b. Antidote of convulsant drugs like strychnine, metrazole,
procaine and cocaine etc.

34 September 29, 2018

 Analgesic Effects
a. Not primarily analgesic but modify the response of patient
to pain
b. Used in combination with other drugs like morphine,
meperidine etc.

35 September 29, 2018

 Respiratory Effects
a. At hypnotic doses, little effects
b. At high doses depress respiratory center (responsiveness
to CO2)
c. Death due to respiratory failure

36 September 29, 2018

 Uterine Effects
a. At low doses, little effects
b. At anaesthetic doses, depress uterine contractions
c. Can cross placenta (diffusion) so may produce foetal
mortality

37 September 29, 2018

 Clinical Uses of Barbiturates
1. Sedatives
2. Hypnotics
3. Anticonvulsants
4. Anaesthetics

38 September 29, 2018

 Toxicity
1. Over dose – death due to respiratory failure
2. Pupil dilated
3. Pulse weak and rapid
4. Reflex disappear
5. Skin cold and cyanotic
Give artificial respiration with 100 % O2

39 September 29, 2018

  Effects of Barbiturates
 Sedation, hypnosis and anesthesia
 Anti-convulsants
 Poor analgesics
 Higher doses can lead to respiratory failure and death. To
treat this, respiratory center stimulants (Doxapram) are
used.
 Therapeutic Uses
 Sedative, hypnotic and anesthetic
 Anti-convulsants (Phenobarbitone, Primidone)

40 September 29, 2018

 Barbiturate used as general
anaesthetics
(Short and Long acting)

41 September 29, 2018

 Pentobarbitone Sodium
(Nembutal)

I. Short duration
II. Orally produce sleep but I/V anaesthesia
III. Commonly used in dogs and cats
IV. Premedication with morphine
V. Doses:
- Small animal: 20 – 35 mg/kg
- Large animal: 15 mg/kg

42 September 29, 2018

 Thiopentone Sodium
(Intraval sodium, Pentothal sodium)
I. Ultra-short acting
II. Require maintenance dose
III. Not used in large animal
IV. Atropine sulphate pre-medication

43 September 29, 2018

 Thialbarbitone
(Kemithal)

I. Short duration
II. Not for large animals
III. Rapid and smooth anaesthesia

44 September 29, 2018

 Others
1. Thiamylal (Suritol)
2. Methohexitone
3. Hexobarbitone
4. Secobarbitone (Seconil)

45 September 29, 2018

 Barbiturates used as Sedatives,
Hypnotics & Anticonvulsants
(Long acting and Intermediate barbiturates)

46 September 29, 2018

 Phenobarbitone
(Luminal sodium)
1) Orally every 6 hrs.
2) Sedative in pruritis
3) Anticonvulsant

Primidone (converted into phenobarbitone in the body)

47 September 29, 2018

 Amylobarbitone
1) Intermediate duration
2) Sedative
3) Basal anaesthetic

48 September 29, 2018

 Barbitone
1) Sedative or hypnotic
2) Short duration
3) Replaced with Phenobarbitone

49 September 29, 2018

 Miscellaneous agents
 Carbamates, alcohols, cyclic ether
 Chloral hydrate
 Meprobamate
 Buspiron
 Zalepion
 Zolpidem

50 September 29, 2018

  Miscellaneous Drugs
 Chloral Hydrate through oral route can be given.
 Chlorobutanol
 Bromides
 Ethyl Alcohol
 Cannabis (Bhang)

51 September 29, 2018

 Non Barbiturate Hypnotics
1. Chloral hydrate
2. Chlorobutanol
3. Paraldehyde
4. Urethane
5. Chloralose
6. Bromides
7. Cannabis
8. Ethyl alcohol
9. Glutethimide
10. Thalidomide
11. Magnessium salts
52 September 29, 2018
 Chloral Hydrate
1. Sedative for large animals
2. Trichloroethanol metabolite
3. Descending depression of CNS
4. Large dose, deep sleep or anaesthesia
5. As pre-anaesthetic medicine
6. Promethazine pre-medication
7. Poor anaesthetic
8. Narrow safety margin
9. Decrease B.P, decrease respiration
10. Irritant, perivascular leakage causes necrosis
11. Doses:
- Horses & cattle: 15 – 45 gms. orally
- Sheep & goat : 2 – 4 gms.
- Dog & cat: 0.15 – 1 gm
53 September 29, 2018
 Chlorobutanol
1. Same effect as Chloral hydrate
2. Less irritant
3. Local anaesthetic
4. Strong antiseptic
5. Analgesic
6. Depress Medulla oblongata & Cerebrum
7. Preservative
8. Antioxidant
9. Gastric sedative
10. Motionsickness in dogs
54 September 29, 2018
 Paraldehyde
1. Potent sedative & hypnotic less than Chloral hydrate
2. Safe
3. Depress only Cerebrum
4. Little analgesic or anaesthetic
5. Calm the exited animals
6. Control convulsions in tetanus, epilepsy, eclampsia,
strychnine poisoning
7. Not an analgesic
8. Have unpleasant odour and taste

55 September 29, 2018

 Urethane or Ethylcarbamate
1. Weak hypnotic
2. Anaesthetic in laboratory animal
3. Rapid and potent
4. Depress the bone marrow and lymphoid organ

56 September 29, 2018

 Chloralose
1. Hypnotic
2. General anaesthesia in lab.
3. Depress motor & sensory spinal centers
4. Safe and prolonged anaesthesia
5. Less depression of heart
6. Duration of action is 20 minutes
7. Dose:
Sheep: 45 – 55 mg/kg
Cats: 60 – 80 mg/kg

57 September 29, 2018

 Bromides
1. Ammonium, calcium, sodium and potassium
2. Hypnotic and sedative properties
3. Depress CNS
4. Not act as analgesic
5. Urinary sedative
6. Bromism
7. Replaced by barbiturates
8. Dose:
Dogs: 0.3 – 0.6 gms. 2 or 3 times daily

58 September 29, 2018

 Cannabis
1. Cannabis sativa
2. Hashih, bhang, marihuana
3. Hypnotic in horse
4. Tincture in gynaecological examination
5. Dose:
Horse: 8 – 15 gms. oraly

59 September 29, 2018

 Ethyl alcohol
1. No importance
2. Toxicological interest
3. Ataxia
4. Unpleasant disposition

60 September 29, 2018

 Glutethimide
1. Hypnotic
2. Moderate duration of action
3. Substitute for barbiturates
4. Human medicine to induce sleep

61 September 29, 2018

 Thalidomide
1. Moderately long acting sedative & hypnotic
2. Rapid onset
3. Foetal abnormalities during pregnancy

62 September 29, 2018

 Magnessium salts
1. Depression of CNS
2. Anaesthesia
3. Depressed respiration & circulation
4. Mg not absorbed from GIT
5. Effect only seen after injection
6. MgSO4 used as general anaesthetic & control convulsions

63 September 29, 2018

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