sedatives & hypnotics by dr. nadeem korai
TRANSCRIPT
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