SEDATIVE &HYPNOTICS

DR.FOUZIA
SEDATIVE & HYPNOTICS

Sedatives (Anxiolytics):
A sedative relieves the anxiety of the person with minimum CNS
depression .

Hypnotics:
A hypnotic produces drowsiness and facilitates onset of sleep
with more pronounced CNS depression
CLASSIFICATION OF SEDATIVE-HYPNOTICS
Based on Receptor Selectivity:
1-GABA Facilitators:
Benzodiazepines (BZD)
Barbiturates
Non-BZD---Z compounds:
Zaleplon
Zolpidem
Eszopiclone
CLASSIFICATIONS OF BZD
BASED ON DURATION OF ACTION
1-SHORT ACTING
Midazolam, Triazolam, Chlorazepate
2-INTERMEDIATE ACTING
Temazepam, Oxazepam, Estazolam, Chlodiazepoxide ,
Alprazolam, Lorazepam
3-LONG ACTING
Clonazepam, Clobazam, Quazepam, Diazepam, Flurazepam
MECHANISM OF ACTION OF BZD
GABA is inhibitory, binds to GABA-A receptor cl channel complex.
BZD bind to GABA receptors between α and ᵞ subunit
Potentiate GABA inhibitory action by ↑ Frequency of cl channel
opening
Agonist at BZD binding site :
BZD , Non-BZD: Z compounds
Antagonist:
Flumazenil, blocks action of both BZD and Non-BZD compounds
PHARMACOLOGICAL EFFECTS OF BZD
1-Sedation
Anxiolytic effects, depression of psychomotor, cognitive
functions
2-Anterograde amnesia:
Recent memory loss
3-Hypnosis:
BZD promote sleep and ↑ the duration of sleep state
4-Anesthesia:
At high doses, loss of consciousness with amnesia and
suppression of reflexes may occur.
PHARMACOLOGICAL EFFECTS OF BZD
5-Anticonvulsant effects:
Suppression of seizure activity with high doses along with
hypnosis may occur.
6-Muscle relaxation:
At high doses, BZDs produce skeletal muscle relaxation
7-Respiratory depression:
High doses may produce medullary depression leading to
respiratory arrest, hypotension.
PHARMACOLOGICAL EFFECTS OF BZD
8-Tolerance:
↓ in responsiveness may occur when used chronically or at high
doses.
9-Psychological dependence:
Intensity may vary from desire to craving
10-Physiological dependence:
It is an altered physiological state that requires continuous drug
administration to prevent an abstinence or withdrawal syndrome
Withdrawal syndrome
Restlessness, anxiety, weakness, orthostatic hypotension and
generalized seizures
THERAPEUTIC INDICATIONS OF BZD
1-Sedatives
For acute anxiety states and rapid control of panic attacks
2-Hypnotics
For treatment of insomnia
3-Medical and surgical procedures
Endoscopy, bronchoscopy (sedative &amnestic effect)
4-Pre-anesthetic medication
Oral formulation of shorter duration are used.
THERAPEUTIC INDICATIONS OF BZD
5- Withdrawal syndrome:
Diazepam is used for withdrawal effects of BZD or Ethanol
6- As Muscle relaxants:
Diazepam produces muscle relaxant effect.
7-As Anticonvulsants:
Status epilepticus due to rapid entery into brain
8-Psychiatric uses
Initial management of mania (part of bipolar disorder)
ADVERSE EFFECTS OF BZD
1- CNS DEPRESSION
Drowsiness
Impaired judgment
Diminished motor skills producing impact on driving, job
Anterograde amnesia(endoscopy)
Hangover
Confusional states in elderly(1/2 dose than youngs)
Lethargy and state of exhaustion
ADVERSE EFFECTS OF BZD
2-Hypersensitivity reactions---skin rashes
3-Pregnancy:
Teratogenic, contraindicated in pregnancy (Category D)
4-Long-term use: Physiologic dependence
5-Withdrawal symptoms:
Restlessness, anxiety, weakness, orthostatic hypotension and
generalized seizures
T/M: Diazepam
6-Treatment of BZD toxicity: Flumazenil (antidote)
CLASSIFICATION OF BARBITURATES
BASED ON DURATION OF ACTION
SHORT ACTING
Methohexital
Thiopental
INTERMEDIATE ACTING
Amobarbital , Pentobarbital , Secobarbital, Butabarbital
LONG ACTING
Phenobarbital
Mephobarbital
BARBITURATES
1-Mechanism of action:
A-Bind to GABA receptors at distinct site and ↑duration of
opening of GABA-mediated chloride channel
B-Inhibits glutamate release
Pharmacological effects:
1-CNS Effects:
CNS depression from sedation to anesthesia and coma in case
of toxicity.
Tolerance
Physical dependence
BARBITURATES
Therapeutic uses of barbiturates:
1-Induction and maintenance of anesthesia
2-Status Epilepticus
3-Neonatal Jaundice or Kernicterus
ADVERSE EFFECTS OF BARBITURATES
1-Drowsiness
2-Distortion of mood and impairment of judgment and fine motor
skills
3-Vertigo, nausea, vomiting or diarrhea
4-Hypersensitivity reactions
5-Rapid I/V –circulatory collapse or even shock
6-Apnoea, laryngospasm and coughing when given for
anesthesia

NO ANTIDOT FOR BARBITURATE TOXICITY

NOVEL BZD RECEPTOR AGONIST
Z-COMPOUNDS
1-Zolpidem
2-Zaleplon
3-Eszopiclone
Therapeutic indications:
Insomnia
BUSPIRONE
1-It has selective anxiolytic effects, no hypnosis, dependence,
muscle relaxation and anticonvulsant property
2-Partial agonist at brain 5-HTA receptors
3-It is safe in pregnancy.
ADVERSE EFFECTS:
1-Nervousness
2-Headache
3-Tinnitus
4-Paresthesia
5-Dizziness