Pharmacology of Sedatives & HYpnotics,Classification, Pharmacological actions, Pharmacokinetics ,USES.

2. SEDATION : It refers to decreased responsiveness to
ay level of stimulation & is associated with some
decrease in motor activity & ideation.
A drug that subdues excitement & calms
the subject without inducing sleep, though
drowsiness maybe produced.
HYPNOTICS : A drug that induces/maintains sleep
similar to normal arousal sleep.

3. CLASSIFICATION
1.Barbiturates (a)Long acting: Phenobarbitone.
(b)Short acting: Butobarbitone ,Pentobarbitone.
(c)Ultra-short acting: Thiopentone ,
Methohexitone.
2.BZD’S (a)Hypnotic: Diazepam, Flurazepam, Nitrazepam,
Triazepam, Temazepam.Alprazolam.
(b)Anti-anxiety: Diazepam, Chlordiazepoxide,
Oxazepam,Lorazepam,Alprazolam.
(c)Anti-Convulsants: Lorazepam, Diazepam,
Clonazepam,Clorazepam.
3.Newer Non-BZD’s: Zopicone,Zolpidem,Zoleplan.

4. Normal Sleep Patterns
Duration & Sleep patterns varies among different individuals .
Two phases are: NREM & REM Sleep.
*NREM (NON RAPID EYEBALL MOVEMENT)
*NREM (RAPID EYEBALL MOVEMENT)

5. BARBITURATES:
Mechanism of action:

6. Barbiturates bind post-synaptically & extrasynaptically .
When endogenous GABA binds to receptor it causes a
conformational changes which opens central pore &
allows cl- ions to pass down the
electrochemical gradient Hyperpolarization.

8. Pharmacological actions
Hangover, Dizziness, Mood distortions,
Euphoria, Restlessness, Mental confusion, Convulsion.
Reduce urine flow by decreasing blood pressure &
increasing ADH release.
Reduced blood pressure, Heart rate, Reflex Tachycardia,
Vasomotor centre depression, Deceased cardiac contractility.
Reduces Muscle contraction
Deceases the muscle tone & Motility of bowel.
@ Higher doses Repiration decreases; Neurogenic,Hypoxic & Hypercapnic drives
to Respiratory centre are depressed. Doesn’t shows Anti-tussive actions.

9. Absorption –Orally well Absorbed.
These crosses the Placenta, Secreted in Milk & produces an effect on
foetus suckling milk.
CNS entry depends on lipid solubility:
Less lipid soluble drugs : Pentobarbitone (Takes longer time).
High lipid soluble drugs : Thiopentone(highly soluble & enters instantly).
Very slow lipid soluble drugs : Phenobarbitone .
Plasma t1/2 is12-40 hrs.(Phenobarbitone has 80-120 hrs)
Metabolism – Oxidation, Dealkylation,Conjugation..
Excretion - Low lipid soluble drugs are excreted unchanged in urine.

10. Hangover, Mental confusion, Impaired peformance,
Tolerance & dependence ,
Hypersensitivity Reactions: Rashes ,Swelling of lips
& eyelids .
Delirium, Dementia, Excitement,
Physical dependence, Halluciations, Convulsions,
Deaths may occur.

11. Theophylline/Warfarin/Tolbutamide/Griesofulvin/Chloramphenicol ++
Barbiturates  Metabolism is induced by Barb.
CNS depressants++ Valproic acid++
Barbiturates  Phenobarb.Increases
Addiction action. Plasma conc. Of
Phenobarbitone.

12. USES
Barbiturates are seldom used now.
Phenobarbitone is used in Epilepsy ;
Thiopentone in Anaesthesia.