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Sedative – Hypnotic Drugs Anxiolytic Drugs Minor Tranquilizers Minor Tranquilizers.

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Presentation on theme: "Sedative – Hypnotic Drugs Anxiolytic Drugs Minor Tranquilizers Minor Tranquilizers."— Presentation transcript:

1 Sedative – Hypnotic Drugs Anxiolytic Drugs Minor Tranquilizers Minor Tranquilizers

2 Sedative – Hypnotic Drugs Spectrum of Activity: Decreased Anxiety. Decreased Anxiety. Sedation. Sedation. Sleep( Hypnosis). Sleep( Hypnosis). Death. Death.

3 Basic Features Overlapping actions. Overlapping actions. General CNS depressants. General CNS depressants. Abuse potential. Abuse potential. Additive effects. Additive effects.

4 Dose-response curves for two hypothetical sedative- hypnotics.

5 Ideal Anxiolytic Calm the patient without too much day time sedation and drowsiness and without producing dependence. Calm the patient without too much day time sedation and drowsiness and without producing dependence.

6 Children's Anxiety Scale PANIC, Panic disorder and agoraphobia; FEARS, Fears of physical injury GAD, generalized anxiety disorder. SAD, separation anxiety disorder SOCPH, social phobia OCD, obsessive–compulsive disorder.

7 Ideal Hypnotic Patient should go asleep quickly. Patient should go asleep quickly. Maintains sleep of sufficient quality and duration. Maintains sleep of sufficient quality and duration. Patient awakes refreshed without hangover( الآثار البغيضة التى تخلف ). Patient awakes refreshed without hangover( الآثار البغيضة التى تخلف ).

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9 Benzodiazepines 200 synthesized(1960s-2000). 200 synthesized(1960s-2000). Receptor is associated with GABA receptor. Receptor is associated with GABA receptor. Increase affinity of GABA for GABA I receptors. Increase affinity of GABA for GABA I receptors. Increase the frequency of Cl- channel opening events leading to hyperpolarization and postsynaptic inhibition and decreased transmission. Increase the frequency of Cl- channel opening events leading to hyperpolarization and postsynaptic inhibition and decreased transmission.

10 GABA A Receptor Chloride ion channel. Chloride ion channel. Pentameric structure assembled from 5 subunits( each with 4 transmembrane-spanning subunits) selected from multiple polypeptide classes(α, β …etc). Pentameric structure assembled from 5 subunits( each with 4 transmembrane-spanning subunits) selected from multiple polypeptide classes(α, β …etc). Subunits of these classes are characterized. Subunits of these classes are characterized.

11 GABA A Receptor Binding sites of GABA are located between adjacent α 1 and β 2 subunits. Binding sites of GABA are located between adjacent α 1 and β 2 subunits. Binding site for benzodiazepines is between α 1 and α 2 subunits. Binding site for benzodiazepines is between α 1 and α 2 subunits. GABA receptors in different areas of the CNS consist of various combinations of the essential subunits. GABA receptors in different areas of the CNS consist of various combinations of the essential subunits. BZs bind to many of these. BZs bind to many of these. Zolpidem binds only to isoforms containing α 1 subunits Zolpidem binds only to isoforms containing α 1 subunits

12 A model of the GABAA receptor-chloride ion channel macromolecular complex

13 Chemical structures of some benzodiazepines

14 Biotransformation of benzodiazepines

15 Benzodiazepines Cause dose-dependant CNS depression. Cause dose-dependant CNS depression. Wide margin of safety. Wide margin of safety. Relatively mildly addictive. Relatively mildly addictive.

16 Adverse Effects of Benzodiazepines CNS depression ----- Tolerance. CNS depression ----- Tolerance. Blurring of vision. Blurring of vision. Hallucinations. Hallucinations. Paradoxical Reactions----- Excitement Paradoxical Reactions----- Excitement GI, Blood ------ Rare. GI, Blood ------ Rare. Additive. Additive. Overdose: Flumazenil. Overdose: Flumazenil.

17 Withdrawal Symptoms of Benzodizepines Rebound Insomnia and Anxiety. Rebound Insomnia and Anxiety. Tremor, N.V., Weight loss, Convulsions. Tremor, N.V., Weight loss, Convulsions.

18 Barbiturates Old fashioned(1930-1960s) sedative- hypnotic drugs. Old fashioned(1930-1960s) sedative- hypnotic drugs. Also facilitate the actions of GABA A at multiple sites but appear to increase the duration of GABA A gated Cl- channel opening. Also facilitate the actions of GABA A at multiple sites but appear to increase the duration of GABA A gated Cl- channel opening. At high concentrations might work directly. At high concentrations might work directly. Might also depress excitatory neurotransmitters like glutamic acid. Might also depress excitatory neurotransmitters like glutamic acid.

19 Barbiturates Hangover Effects Hangover Effects Deaths were(1960s) common, Drug Automatism Deaths were(1960s) common, Drug Automatism Abuse, Tolerance, Dependence and Withdrawal. Abuse, Tolerance, Dependence and Withdrawal. Interactions are common, can induce liver enzymes. Interactions are common, can induce liver enzymes.

20 Barbiturates Thiopental Thiopental Amobarbital Amobarbital Pentobarbital Pentobarbital Phenobarbital Phenobarbital Differ in durations of action and consequently in their uses. Differ in durations of action and consequently in their uses.

21 Chemical structures of some barbiturates and other sedative-hypnotics.

22 Buspirone Anxiolytic, needs a week to work. Anxiolytic, needs a week to work. No sedative, anticonvulsant or muscle relaxant effects. No sedative, anticonvulsant or muscle relaxant effects. 5HTA1A partial agonist. Works also on D2 receptors. 5HTA1A partial agonist. Works also on D2 receptors. Safe: Tachycardia, GIT distress, paresthesia and pupillary constriction. Safe: Tachycardia, GIT distress, paresthesia and pupillary constriction. No dependence or tolerance. No dependence or tolerance. No rebound or withdrawal. No rebound or withdrawal. No additive effects to others. No additive effects to others. Minimal abuse liability. Minimal abuse liability.

23 Zolpidem Good sedative. Good sedative. Wide spectrum but weak. Wide spectrum but weak. Binds to benzodiazepine receptor. Binds to benzodiazepine receptor. Short acting. Short acting. Preserves normal sleep. Preserves normal sleep. GI side effects (diarrhea). GI side effects (diarrhea).

24 Ramelteon Melatonin receptor agonist (MT1 and MT2). Melatonin receptor agonist (MT1 and MT2). Not a controlled substance. Not a controlled substance. Melatonin involved in circadian rhythm. Melatonin involved in circadian rhythm. Effects on sleep and endocrine system. Effects on sleep and endocrine system. Might be useful for jet lag. Might be useful for jet lag.

25 Chemical structures of newer hypnotics

26 Antihistamines Hydroxyzine Hydroxyzine Diphenhydramine. Diphenhydramine. Promethazine. Promethazine. These are non addictive, uncontrolled drugs( over the counter), and have anticholinergic side effects.

27 - adrenergic Blockers - adrenergic Blockers Best drugs for Performance Anxiety (Stage Fright). Best drugs for Performance Anxiety (Stage Fright). Will inhibit the symptoms of sympathetic activity associated with anxiety(nervousness, palpitations, sweating, tremor, coldness) Will inhibit the symptoms of sympathetic activity associated with anxiety(nervousness, palpitations, sweating, tremor, coldness) Will not affect the level of consciousness. Will not affect the level of consciousness.

28 Antidepressants General anxiety. General anxiety. Phobic( الرهاب ) and Panic الرعب ) (Disorders. Phobic( الرهاب ) and Panic الرعب ) (Disorders. Obsessive-compulsive states. Obsessive-compulsive states.

29 Chloral Hydrate 1800. 1800. Effective. Effective. TCE. TCE. Sharp smell and taste, gastric irritation, allergy, arrhythmia. Sharp smell and taste, gastric irritation, allergy, arrhythmia.

30 Paraldehyde. Paraldehyde. Meprobamate: Meprobamate: Muscle Relaxant, 1951 Geriatric patients.

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