Sedative-hypnotic drugs reduce anxiety and induce sleep by depressing activity in the central nervous system. The main classes are benzodiazepines, barbiturates, and newer non-benzodiazepine agents. Benzodiazepines have largely replaced barbiturates due to their wider therapeutic index, lower risk of interactions and dependence, and the availability of antagonists. Both benzodiazepines and barbiturates work by enhancing the effects of the inhibitory neurotransmitter GABA.

1. Sedative- Hypnotic Drugs
Drug that cause sleep and reduce anxiety are
called sedative-hypnotic .
OR
Sedative-hypnotic, a sedative that depresses
activity of the central nervous system and reduces
anxiety and induces sleep.

2. Basic Pharmacology of Sedative-
Hypnotics
Sedative (Anxiolytic): decrease activity, calming
effect.
An Anxiolytic agent should reduce anxiety
An Anxiolytic should exert a calming effect with
little or no effects on motor or mental functions.
Depression of CNS should be the minimum
consistent with therapeutic efficacy.

3. • Hypnotic: induce sleep
A Hypnotic drug should produce drowsiness.
Should encourage the onset and maintenance
of a state of sleep that resembles the natural
sleep states.
CNS depression should be more pronounced
than sedation.
(all Sedative- Hypnotics can cross the placenta)

4. HYPNOSIS
• Hypnosis is a subconscious condition in
which the objective manifestations of the
mind are more or less inactive,
accompanied by abnormal sensitivity.

5. Classification of Hypnotic- Sedatives
The main groups of drugs are:
 Benzodiazepines
 Barbiturates
 Newer Agents

6. Classification of Hypnotic- Sedatives
I. Benzodiazepines
• Diazepam
• Clonazepam
• Oxazepam
• Clobazam
• Clordiazepoxide
• Midazolam
properties
 High therapeutic index( high
LD50)
 Relatively safe in overdose
 Less hangover
 Slowly developing tolerance
 Less addiction liability

7. Classification of Hypnotic- Sedatives
II. Barbiturates
• Phenobarbitone
• Amobarbital
• Thiopental- Na
properties
 Nonselective CNS
depressants
 less therapeutic index( not
safe)
 Marked hangover
 Enzyme inducer, so rapidly
develops tolerance
 Addiction liability marked
 Acute over dose causes
cardio respiratory failure

8. Classification of Hypnotic- Sedatives
III. Newer agents
• Non Benzodiazepines
• Zolpidem
• Zaleplon
• Buspirone
IV. Chloral hydrate
V. Paraldehyde
VI. Diphenhydramine
Properties
• Act through non-GABA ergic
systems
• Less drowsiness and
dependence
• anxiolytic

9. The ideal anxiolytic drug:
Should calm the patient without causing too
much day time sedation and drowsiness.
 Should not interact with other medications in
such away as to produce unwanted or
dangerous effect.
Without producing physical or psychological
dependence.
Should have very low toxicity

10. The ideal hypnotic drug:
• Should allow the patient to fall asleep quickly.
• Should maintain sleep of sufficient quality and
duration so that the patient awakes refreshed
without a drug hangover) feeling of tiredness
well after the patient wakes. This may lead to
impaired ability to function normally for many
hours after waking. Occasionally, nausea and
dizziness occur.

11. Barbiturates
• They have been largely replaced by the benzodiazepines,
because Barbiturates:
• 1. Low therapeutic index.
• 2. Induce tolerance, Physical dependence, Very severe
withdrawal symptoms
• 3. Induce drug-metabolizing enzymes.
• 4. Ability to cause coma in toxic doses.
• 5. When used as hypnotics, they suppress REM sleep more
than other stages. Certain barbiturates, such as the very
short-acting thiopental, are still used to induce anesthesia

12. Classification of Barbiturates
Barbiturates are classified according to their duration
of action into:
I. Ultra short acting Barbiturates
• Thiopental-Na
Properties
• High lipid soluble, so
• High rate of entry into the
CNS, so
• Rapid onset of CNS
effects(Acts within second)
• Duration of action: 30
second
• Quickly metabolized by
liver(hence called Ultra
short acting)
• Main use: Intravenous

13. Classification of Barbiturates
II. Short acting:
• Pentobarbital
• Secobarbital
• Hexobarbital
III. Intermediate acting:
• Amobarbital
• Butabarbital
IV. Long acting:
• Phenobarbital
• Barbital
Properties
• Duration of action: (2 hours)
• Main use: as sedatives
• -------------------------------------
• Duration of action: (3-5 hours)
• Main use: as hypnotic
• ----------------------------------
• Duration of action: (>6 hours)
• Main use: as anticonvulsant

14. Mechanism of action of Barbiturates
Barbiturates+ GABA-receptor
↓
Activation of GABA-receptor
↓
Opening of Chloride channel increase the duration of
GABA gated channels opening
↓
Hyper polarization of cells
↓
Depression of the CNS

16. Overview of the mechanism of action Barbiturates. (GAMA: Gamma
amino butyric Acid, an inhibitory neurotransmitter in the brain)

17. Pharmacological actions of Barbiturates
Action on-
• CNS: 1. Mild degree of sedation to
general anesthesia
2. Anticonvulsant effects
3. Respiratory centre
depression ( Respiratory
failure)

18. Pharmacological actions of Barbiturates
Actions on-
• CVS
• Liver
1. Hypotension
2. Decrease heart rate
3. Circulatory collapse
1.Enzyme induction, so
increase metabolism of
itself and other drugs
2. Stimulate glucoronyl
transferase

19. Pharmacological actions of Barbiturates
Actions on-
• Eye
• kidney
1. No effect(normal dose)
2. Miosis (toxic dose)
1. Anti diuretic effect

20. Disadvantages of Barbiturate as
Hypnotic
1. Low TI, i.e relatively small doses endangers the
life and causes respiratory depression
2. Drug of social abuse
3. Physical depence occurs with withdrawal
syndrome
4. Induces hepatic microsomal enzyme, so it is a
source of drug interaction and development of
tolerance

21. 5. Generalized CNS depressant
6.Marked hangover
7. Chance of more suicidal tendency.

22. Indication of Barbiturates
1. As anticonvulsants-
Tetanus
Epilepsy
Eclampsia
2. Intravenous anaesthesia (thiopental- Na)
3. Hyperbilirubinaemia
4.Kernicterus (children)
5.Hemolytic jaundice
6.cholestasis

23. • Barbiturates stimulate liver glucoronyl
transferase which is responsible for bilirubin
metabolism, that is why barbiturates are used
in Hyperbilirubinaemia, kernicterus and
jaundice.

24. Contraindications of Barbiturates
• Acute porphyria (Barbiturate potentiate
porphyrin synthesis)
• Severe pulmonary insufficiency
• Congestive cardiac failure
• Hypovolumic shock
• Renal failure
• Hepatic failure

25. Adverse effects of Barbiturates
1. Hangover-
-drowsiness
-lethargy
-weakness
-disorientation
Lack of concentration
2. automatism(accidental poisoning)
3.Addiction liability(physical & psychological
dependence)
4. Enzyme induction, so rapid tolerance develop.

26. Barbiturates poisoning
• Due to administration of 10-100 times of
clinically used dose.
• Death comes from cardio respiratory failure

27. Sign & symptoms of Barbiturate
poisoning
• CNS
• CVS
1. Drowsiness
2. Respiratory depression
3. Slow & shallow breating
4. Coma
1.Cardiovascular collapse
2. Hypotension
3.Shock
4. dehydration

28. • Lungs
• Kidney
• Temperature
• eye
1. Pulmonary edema
2. Bronchopneumonia
1.Severe oliguria/anuria
2.Renal failure
1. Hypothermia
1.Miosis
2.Hypoxic paralytic dilatation
3. Light reflex present

29. Treatment of Barbiturate poisoning
General measure:
1. O2 inhalation
2. Stabiles' artificial respiration
3. Give stomach wash by KMnO4
4. Activated charcoal
5. Use specific antidote. Inj. Bemigride
6. Establish intravenous channel

30. Treatment
1. Give antibiotic: to prevent pulmonary infection
2. Use cardiotonic agent (if patient is in shock)-
inject Dopamine. Dopamine also increases renal
blood flow.
3. Forced alkaline diuresis:
Barbiturates is an acidic drug. In alkaline urine the
ionization of barbiturates is more. Ionized drugs
are less lipid soluble. So, less reabsorption from
renal tubules and hence more excretion occur.

31. Benzodiazepines replaced barbiturates as
hypnotic-sedative agent. Explain?
• Drawbacks of barbiturates as hypnotic-
sedative are-
1. More pronounced central depressant action
2. Barbiturates have narrow therapeutic index.
3. Non-selective CNS depressant Barbiturates
also depress the action of excitatory
neurotransmitter. So,
4. Acute overdose cause cardio respiratory
depression and coma which ends in death.

32. 5. Develops rapid tolerance due to enzyme
induction.
6. Addiction liability is greater with barbiturates.
7. Hangover is marked with barbiturates.

33. What is drug automatism?
• Barbiturates cause drowsiness, confusion and
amnesia( inability to remember events
occurring during the drug action). So, the
patient take the drug repeatedly and thus
poisoned himself. This phenomenon is known
as drug automatism.

34. Benzodiazepines
• They are the most widely used anxiolytic drugs. They
have largely replaced barbiturates because:
1.The benzodiazepines are safer (have a wide
therapeutic index) and more effective
2. Not cause drug –drug interaction(not induce hepatic
microsomal enzyme)
3. Produce tolerance and psychological dependence
but physical dependence and withdrawal symptom
are less marked
4. Benzodiazepine antagonist is available

35. Benzodiazepines
are classified according to their duration of
action into :
• Short –acting : Oxazepam, Triazolam (3-8)
hours
• Intermediate –acting: Alprazolam, Lorazepam,
Temazepam (10-20) hours
• Long-acting: Chlordiazepoxide, Diazepam,
Flurazepam

36. Mechanism of action of
Benzodiazepine:
• Binding of GABA to its receptor triggers an
opening of a chloride channel, which leads to
an increase in chloride conductance.
Benzodiazepines increase the frequency of
channel openings produced by GABA. The
influx of chloride ions causes a small
hyperpolarization, inhibits the formation of
action potentials.

37. Pharmacological action of BDZ
1.Reduction of anxiety:
• At low doses, the benzodiazepines are anxiolytic.
• They are thought to reduce anxiety by selectively
inhibiting neuronal circuits in the limbic system of
the brain.
2. Sedative and hypnotic actions:
• All of the benzodiazepines used to treat anxiety
have some sedative properties, and some can
produce hypnosis at higher doses.

38. 3. Anticonvulsant:
• some are used to treat epilepsy (status
epilepticus) and other seizure disorders.
4. Muscle relaxant:
• At high doses, the benzodiazepines relax the
spasticity of skeletal muscle

39. Therapeutic uses of BDZ
• Benzodiazepines are effective for the
treatment of the anxiety symptoms
-secondary to panic disorder
-generalized anxiety disorder
-specific phobias, such as fear of flying.
• Midazolam is an injectable only
benzodiazepine also used for the induction of
anesthesia

40. Adverse effects of BDZ
• Drowsiness and confusion: Ataxia occurs at
high doses.
• Psychological and physical dependence on
benzodiazepines can develop if high doses of
the drugs are given over a prolonged period.
• Abrupt discontinuation of the
benzodiazepines results in withdrawal
symptoms, including confusion, anxiety,
agitation, restlessness, insomnia, tension.

41. Benzodiazepine Antagonist
Flumazenil (is a GABAreceptor antagonist) that
can rapidly reverse the effects of
benzodiazepines (competitively occupies a
GABA-receptor without causing a functional
change in CL channel). The drug is available
for intravenous administration only. Onset is
rapid but duration is short, with a half-life of
about 1 hour. Frequent administration may be
necessary to maintain reversal of a long-acting
benzodiazepine

42. • Side effects of Flumazenil:
1.Dizziness, nausea, vomiting, and agitation are
the most common.
2.Withdrawal in dependent patients
3.Seizures:
- If a benzodiazepine is used to control seizure
activity
- -If the patient ingests tricyclic antidepressants.