Chapter 9 Anxiolytics and Hypnotics Drugs. Dr. Shereen Ayoub Faculty of Medicine Al-Azhar University. Causes of Anxiety. 1). Medical : Respiratory Endocrine Cardiovascular Metabolic Neurologic. Causes of Anxiety. 2). Drug-Induced : Stimulants Amphetamines, cocaine, TCAs, caffeine.
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Dr. Shereen Ayoub
Faculty of Medicine
3). Drug Withdrawal:
Hypnotics: agent that induces sleep
sleeping pills, sedative medications, sedative-hypnotics
Various antianxiety agents (minor tranquilizers, psychosedatives) have been used throughout the ages to alleviate feelings of stress, anxiety, discomfort, etc
Currently, benzodiazepines are among the most widely prescribed antianxiety drugs because of their higher therapeutic index (severe CNS depressant doses/antianxiety doses) than older agents
Figure 22-1. Dose-response curves for two hypothetical sedative-hypnotics
Studies (largely in knockout animals—with specific subunit deletions or animals with variant alleles of specific subunits) indicate (strongly suggest) functional specificity of different GABAA subunits:
● α1 subunit-containing GABAA receptors:sedation
● α2 subunit-:anxiolysis.
● α3 subunit-: processing of sensory motor information related to a schizophrenia endophenotype.
● α4 subunit-: sedative, hypnotic and anesthetic effects of some agents in the thalamus.
● α5 subunit- (extrasynaptic): associative temporal and spatial memory by inhibitory modulation of activities in the hippocampus.
● β3 subunit-: sedation, hypnosis and anesthesia by, e.g., pentobarbital, propofol and etomidate, but not by the neurosteroidal anesthetic alphaxalone).
Panic Disorder (alprazolam)
Muscular spasms (duiazepam)
Seizure Disorders, epilepsy (clonazepam , diazepam)
Conscious Sedation insomnia (flurazepam long acting, temazepam intermediate, triazolam short)Benzodiazepines-Indications
Hypnotics may be indicated in insomnia, the major symptoms of which include inability to initiate asleep or stay asleep once initiated (i.e., frequent/premature awakenings). Causes of insomnia include organic and psychological disorders, life style, environmental factors)
A. Physiology of sleep:
The awake state: maintained largely by the arousal system (reticular formation) of the brain stem.
Induction and maintenance of sleep: involves (i) active inhibition of pathways involved in wakefulness and arousal (e.g., serotonergic, muscarinic, adrenergic, histaminic and dopaminergic systems), and (ii) specific brain nuclei (e.g., median raphe nucleus of the lower brain stem).
1. Stages of sleep:
• Non-rapid eye movement (NREM) sleep: accounts for 70-75% total sleep duration and progresses through 4 stages: -Stage I (~5-10 min duration), Stage II (~15 min duration), Stages III and IV (Slow wave sleep; ~ 70 min)
• Rapid eye movement (REM; paradoxical) sleep: a sleep phase during which most dreams occur
• Nonpharmacological approaches: include good “sleep hygiene” (e.g., constant bedtime, avoidance of stimulants immediately prior to bedtime, etc)
• Pharmacological approaches: The “ideal” hypnotic drug should have - a rapid onset of action - minimal effect on normal sleep pattern/stages - the ability to sustain sleep of normal duration - no hangover, daytime sedative effects, or memory impairment potential - minimal addiction or tolerance potential and rebound insomnia - a high therapeutic index
• Effects of most hypnotics on sleep pattern: ↓ onset latency, ↑ NREM duration, ↓ REM duration
Barbiturates, at high concentrations, directly activate the GABAA receptor to enhance chloride permeability-- in addition to allosteric modulation of the GABAA receptor
- Nonspecific neuronal depression has been reported at highly very high (toxic) doses
5. Neonatal hyperbilirubinemia and kernicterus.*
• Barbiturate poisoning: common in suicide attempts; commonly managed by supporting respiration and urine alkalinization (via bicarbonate administration).
- barbiturates and other potent inducers of cytochrome P450 are contraindicated in acute intermittent porphyria: an inherited toxicity syndrome that results in accumulation of porphyrrin and porphyrrin precursors (due to abnormal regulation of porphyrin synthesis). In affected subjects, porphyrins and their precursors accumulate and trigger neural and other symptoms
• neural lesions: widespread demyelination of peripheral and cranial nerves
paralysis and widespread CNS lesions.
• skin and soft tissues lesions
- Other contraindications: concomitant CNS depressants