SEDATIVES & HYPNOTICS

Dr. Nadeem akhtar MBBS.M.Phil

Asst. Professor PharmacologyAmna Inayat Medical College

Shaikhupura

• Chemically heterogeneous class of drugs produce dose dependant CNS

depressant effect, relieve anxiety and induce sleep

Benzodiazepines

(Long acting 1-3 days)Diazepam,Flurazepam,Clonazepam,

Quazepam,Clorazepate (Intermediate 24 hrs)Temazepam,Alprazolam,Nitrazepam (Short acting 12-24 hrs)Lorazepam,Estazolam, Oxazepam (ultra short 6 hrs)

Major groups

• Benzodiazepines

• Barbiturates

• Miscellaneous

Benzodiazepine receptors

• High affinity site for benzodiazepines.

• Located in thalamus, cerebral cortex, limbic system.

• These receptors facilitate inhibitory action of GABA.

Benzodiazepine receptors

• 1) BZ 1 (mediate hypnotic action)

• 2) BZ 2 (memory, sensory and motor activity, cognitive functions)

Mechanism of action

• Potentiate GABA

• Increase the frequency of CL ion channel

• Act through BZ receptors

Pharmacological actions

• A)CNS: cns effects depends on the doseSedation & anti-anxiety effect on small dosesHypnotic action is produced on high doses, by

decrease REM sleep & increase stage 2 NREM Sleep (deep sleep). Anesthetic action produced by Midazolam with

amnesia.

Pharmacological action

• Anticonvulsant effect produced by Diazepam.

• Muscle relaxant effect occur due to centrally inhibitory action on synaptic reflexes, high doses depress transmission on neuromuscular junction.

Pharmacological action

• CVS & Respiration: In a healthy person this have no effect up to

hypnotic doses, at toxic doses medullray depression occur leading to respiratory arrest (uncommon with BZ)

Clinical uses

• For sedation and amnesia as pre-op management (diazepam, lorazepam, midazolam)

• Alcohol withdrawal states (diazepam, oxazepam and chlorodiazepoxide)

Clinical uses

• Anti-anxiety with depressive symptoms (alprazolam).

• Insomnia (Flurazepam, Temazepam, Triazolam).

• Panic disorder (alprazolam)• Epilepsy (lorazepam i.v in status epilepticus)

Adverse effects

• Drowsiness• Ataxia• Day time sedation leading to fall amd fractures in

elderly patients• Amnesia• Confusion • Diminished motor skills• Psychological & physical dependence• Depression and suicidal thoughts

Flumazenil

• This compound reverses the action of BZs therefore acts as anti-dote to the drug, used extensively in anesthesia for recovery of patient. Also known as GABA receptor antagonist.

• Given i.v in BZs overdose.• Having short half life of 1 hr so given

repetitively.

Contraindications

• Glaucoma• CLD• Allergy to BZs

Pharmacokinetics

• Liver metabolized to active compounds, except for oxazepam, temazepam, and lorazepam

Barbiturates

Long actingBarbital, Phenobarbital, Methylphenobarbital. IntermediateAmylobarbital, amobarbital, butabarbital Short actingPentobarbital,Hexobarbital, Thiopentol,

Thiamylal

Mechanism of action

• Depress neuronal activity in reticular system.• Facilitate and prolong GABA action• Increase duration of GABA mediated CL ion

channel opening.• Block excitatory neurotransmitter Glutamic

acid

Pharmacological action

• CNS• Low dose------------ sedation & anti-anxiety

• High dose------------- hypnosis

• Large dose----------- anesthesia, coma, death

Pharmacological action

• CVS• As the dose increases, depress the ganglion

tranmission then decrase heart rate and BP• Respiration• This is a potent respiratory depressant and

decrease the sensitivity of respiratory centers to CO2.

Pharmacological action

• Kidney Decrease urine out put at large doses due to

hypotension & release of ADH.

• Blood Can Induce porphyria

Clinical uses

• Generalized anxiety• Insomnia• Convulsion• Cerebral edema• Induction of anesthesia• Hyperbilirubinemia in kerncteris in new born

Adverse effects

• Due to over sedation ,diminished concentration.

• Severe withdrawal reactions characterized by seizures, tremors, hallucinations and psychosis

• Skin eruptions & porpyrias

Barbiturates poisoning

• Treatment• Stomach wash• Alkalinizing urine, promoting drug excretion.• Hemo or peritoneal dialysis

Contraindications

• Advanced liver or kidney disease• COPD• Porphyria

Miscellaneous agents

• Chloral hydrate

• Buspirone

• Zolpidem

Chloral hydrate

• This is a derivative of ethyl alcohol, given in solution or in capsule absorbed from intestine and reduced to trichloroethanol which produce hypnotic action.

• Indicated in children and elderly patients• Produce gastric irritation

Buspirone

• Buspirone don't interact directly with GABA system

• Acts through partial agonist at 5-HT receptors• It relives anxiety without producing hypnotic

and sedative effect• Anti-anxiety effect may take more than a

week

Zolpidem

• Structurally not related to benzodiazepine• Acts on subset of benzodiazepine BZ1

receptor.• This has no muscle relaxant or anti-conversant

property.• It shows few withdrawal effects.• Rapidly absorb from GIT• Rapid onset of action