SEDATIVE/HYPNOTICS ANXIOLYTICS

SEDATIVE/HYPNOTICS ANXIOLYTICS
By:Martha I. Dávila-García, Ph.D.
Department of Pharmacology, Howard University

Optimal Performance Nervous Breakdown
Performance Anxiety GOAL
SEDATIVE/HYPNOTICS ANXIOLYTICS
Manifestations of anxiety:
Pathological Anxiety
Causes of Anxiety
1). Medical:
o Respiratory
o Endocrine
o Cardiovascular
o Metabolic
o Neurologic.

2). Drug-Induced:
o Stimulants
+ Amphetamines, cocaine, TCAs, caffeine.
o Sympathomimetics
+ Ephedrine, epinephrine, pseudoephedrine phenylpropanolamine.
o Anticholinergics\Antihistaminergics
+ Trihexyphenidyl, benztropine, meperidine diphenhydramine, oxybutinin.
o Dopaminergics
+ Amantadine, bromocriptine, L-Dopa, carbid/levodopa.
o Miscellaneous:
+ Baclofen, cycloserine, hallucinogens, indomethacin.

3). Drug Withdrawal:
Anxiolytics
Sedative/Hypnotics
Properties of Sedative/Hypnotics in Sleep
1) The latency of sleep onset is decreased (time to fall asleep).
2) The duration of stage 2 NREM sleep is increased.
3) The duration of REM sleep is decreased.
4) The duration of slow-wave sleep (when somnambulism and nightmares occur) is decreased.
Other Properties of Sedative/Hypnotics
GABAergic SYSTEM
Benzodiazepines
* Diazepam
* Triazolam
* Lorazepam
* Alprazolam
* Clorazepate => nordiazepam
* Halazepam
* Clonazepam
* Oxazepam
* Prazepam
Barbiturates
* Phenobarbital
* Pentobarbital
* Amobarbital
* Mephobarbital
* Secobarbital
* Aprobarbital
Respiratory Depression
Coma/Anesthesia
Ataxia
Sedation
Anxiolytic
Anticonvulsant
DOSE
RESPONSE
BARBS
BDZs
ETOH
GABAergic SYNAPSE
GABA
glutamate
glucose
GAD
GABA-A Receptor
GABA AGONISTS BDZs
Mechanisms of Action
Benzodiazepines
PHARMACOLOGY
* BDZs potentiate GABAergic inhibition at all levels of the neuraxis.
* BDZs cause more frequent openings of the GABA-Cl- channel via membrane hyperpolarization, and increased receptor affinity for GABA.
* BDZs act on BZ1 (1 and 2 subunit-containing) and BZ2 (5 subunit-containing) receptors.
* May cause euphoria, impaired judgement, loss of cell control and anterograde amnesic effects.

Pharmacokinetics of Benzodiazepines
CNS Effects
Lipid solubility
Biotransformation of Benzodiazepines
Properties of Benzodiazepines
Side Effects of Benzodiazepines
Toxicity/Overdose with Benzodiazepines
Drug-Drug Interactions with BDZs
Pharmacokinetics of Barbiturates
Properties of Barbiturates Mechanism of Action.
Toxicity/Overdose
Miscellaneous Drugs
* Buspirone
* Chloral hydrate
* Hydroxyzine
* Meprobamate (Similar to BARBS)
* Zolpidem (BZ1 selective)
* Zaleplon (BZ1 selective)
Properties of Other drugs.
OTHER USES
ANXYOLITICS
Alprazolam
Chlordiazepoxide
Buspirone
Diazepam
Lorazepam
Oxazepam
Triazolam
Phenobarbital
Halazepam
Prazepam
HYPNOTICS
Chloral hydrate
Estazolam
Flurazepam
Pentobarbital
Lorazepam
Quazepam
Triazolam
Secobarbital
Temazepam
Zolpidem
References:

SEDATIVE/HYPNOTICS ANXIOLYTICS.ppt