Sedatives and Hypnotics

Dr. Maged Bin Harize

 definition:

 Sedatives : Drugs that cause sedation and

calm behavior BUT produce drowsiness.
 Hypnotics : Drugs that induce sleep.
They are used primarily to treat anxiety and
insomnia.
Sedative-hypnotic drugs : in Small Dose
(Sedative) & in large dose (Hypnotic).
Characteristics of an Ideal Hypnotic:
1 - Orally
2- Rapid onset
3- Adequate duration
4- Normal sleep pattern
5- No hangover
6- No tolerance
7- No Dependence
8- N o adverse effects
 Classification According to Mechanism of Action

I. Drugs Facilitating II. 5-HT1A II. Melatonin

GABA Agonist/Partial Receptor agonist
Agonist

 Barbiturates  Buspirone  Ramelteon

 Benzodiazepines (BZDs)

 Non Benzodiazepines
Zolpidem - Zaleplon.

 Alcohol
Benzodiazepines (BZDs)
 Classification of BZs
Class Drugs
Short acting (t1/2 = 5h) Midazolam
trizolam
Alprozolam
Colonazepam
intermediate acting (t1/2 = 5-24 h) Estazolam
Lorazepam
Oxazepam
temazepam

Chlordiazepoxide
Chlorazepate
Long acting (t1/2 > 24) Diazepam
Flurazepam
Prazepam
quazepam
 Mechanism of action
CL

Barbiturate Benzodiazepine
 Pharmacological Actions of Bz:

sedation
Sleep
amnesia
Skeletal Muscle Relaxation: Diazepam &
Clonazepam
Anticonvulsant & Antiepileptic effect:
Antidepressant:alprozolam
Respiratory effect
CVS effect
 Therapeutic Uses of Bz:

 Anxiety
insomnia
Pre anesthetic medication
Anti- spasticity agent
Anticonvulsant & Anti-Epileptic
Analgesics
Alcohol withdrawal
 Adverse Effects of Bz :
 Tolerance
 Dependence
 rebound insomnia
 Hangover
 Amnesia
 severe CNS Depression &CVS & Respiration
depression.
 Ataxia &↑motor skills
 Increases Appetite
 Amenorrhea, decreased Ovulation, decreased Ejaculation
 teratogenic
 Allergy
 Flumazenil

 Selective and competitive block of Bz-receptors

 It has no effect on other CNS depressants e.g.
Barbiturates.
 used IV (0 .3 -1 mg).
 Extensive (80%) hepatic first pass metabolism.
 Short t1/2 = 1 hour,
 Withdrawal syndrome
 Non-benzodiazepines
• Bz1 receptor agonists : Zolpidem, Zaleplon,
Zopiclone, Eszopiclone.
 Selective Hypnotic.
 Not alter sleep stages.
 Minimal muscle relaxation or anticonvulsant.
 Minimal tolerance & dependence
 Short acting (t1/2 = 2 hrs.) and Rapid onset
 Can be antagonized by Flumazenil.
 side effects :nightmares, GIT upset, dizziness and
day time drowsiness.
 Buspirone
 Partial agonist on presynaptic 5-HT 1A-receptor in
mid brain.
 slow onset of action(1-2 week)
 Selective anxiolytic, it is anxiolytic choice in the
elderly
 Effective in generalized anxiety syndrome when
delayed onset is accepted.
 not cause side effect as BZs.
 Does not treat insomnia or panic attacks
 Side effects→ Nervousness, tachycardia & GIT
distress, serotonin syndrome.
 Ramelteon:

 Hypnotic; selective agonist at MT1 &MT2

melatonin receptors in the brain →↓Latency to
persistent sleep→ useful in patients with
difficulty in falling asleep
 It is used mainly as hypnotic in children and
elderly .
 Minimal abuse potential (not a controlled
substance)
 Side effects: dizziness, somnolence ,fatigue and
endocrine change(increase prolactin and decrease
testosterone)
 Barbiturates

 Barbituric acid (Malonylu rea) is not active.

 Formerly used as sedative-hypnotics but
largely replaced by BZDs due to:
Narrow therapeutic index (BZDs are safer)
No specific antidote
Drug dependence
Enzyme induction → drug interactions.
Acute porphyria :
 Classification of Barbiturates

Ultra short-acting: thiopental (t1/2 15-20 min)

Short-acting (t1/2 :4h) pentobarbital, secobarbital
Intermediate: (t1/2 ~ 6-8 h)butabital ,Amobrbital.
Long-acting: (t1/2 1-2d) phenobarbital
 Actions of Barbiturates on C.N.S :

 Sedative action BUT→ Drowsiness.

 Hypnotic action BUT Abnormal sleep
 Hang-over.
 Rebound paradoxical sleep after tolerance or
stopping the drug .
 Amnesia.
 General anesthesia
 Anti-Epileptic
 Potentiate analgesics.
 Therapeutics uses

 Anesthesia
epilepsy, Status epilepticus and convulsions.
 hyperbilirubinaemia in neonate.
used currently as lethal dose
 Adverse Effects of Barbiturates :

 idiosyncrasy →Acute Porphyria in patients with

Acute Intermittent Porphyria.
 Tolerance
 Dependence
 Rebound insomnia
 Amnesia.
 Hang-over
 Drug Interactions.
 Allergy.
 Acute Poisoning
 Drug Interactions :

decrease effect of some drugs e . g

anticoagulants, hypoglycemic & contraceptives.
Barbiturates + Ethyl alcohol .
Barbiturates + Aspirin →Potentiation .
Barbiturates + Caffeine.