Hypnotic drugs in clinical practice
In medical practice, hypnotic drugs are used to treat sleep-onset disorders. These are specialized medicinal substances that induce a specific state of the central nervous system. The main requirement for such drugs is that the state they induce must be as close as possible in its characteristics to the natural physiological process.
The primary indication for prescribing hypnotic medications is various forms of insomnia, which in medicine are referred to as insomnia. When administering pharmacotherapy, the physician pursues two fundamental objectives:
- Induction — substantially facilitating the process of falling asleep itself.
- Maintenance — ensuring a sufficient and continuous duration of rest.
Physiological architecture: phase alternation
Electroencephalography (EEG) data conclusively prove that nighttime rest is not a homogeneous process. Depending on the nature of brain wave activity, two regularly alternating phases are distinguished.
1. Slow-wave sleep (Non-REM sleep) In scientific literature, this phase is also called slow, orthodox, or synchronized sleep. It dominates the structure of nighttime rest, accounting for 75 to 80 percent of the total time. The development of the orthodox phase does not occur all at once, but strictly sequentially, passing through four stages:
- It begins with stage 1, which represents light drowsiness.
- It gradually deepens up to stage 4, which is called delta sleep. At this stage, the EEG records the appearance of characteristic slow, high-amplitude $\delta$-waves.
2. Fast-wave sleep (REM sleep) Its synonyms are rapid, paradoxical, or desynchronized sleep. The paradoxical phase accounts for about 20–25 percent of total rest time. It is this period that is accompanied by vivid dreams. A characteristic clinical marker of the phase is rapid eye movements (hence the English abbreviation rapid eye movement). Episodes of desynchronized activity follow a strict cyclicity, repeating every 80–90 minutes.
Neurochemical control of sleep and wakefulness
The alternation of orthodox and paradoxical phases, as well as the maintenance of stable rest, is controlled by a complex set of neurotransmitters and peptides. The balance of these substances determines the quality of central nervous system recovery.
- Serotonin: acts as a key factor that primarily induces (triggers) the sleep onset process.
- Melatonin: a hormone that ensures phase synchronization and fine-tuning of circadian rhythms.
- Inhibitory and opioid systems: gamma-aminobutyric acid (GABA), endorphins, and enkephalins. They provide the necessary inhibition of the central nervous system.
- Specific factors: for example, the delta-sleep-inducing peptide, which regulates the deep stages of the slow phase.
- Wakefulness and modulation mediators: this group includes acetylcholine, dopamine, adrenaline, and histamine. Their activation leads to the termination of rest.
Clinical typology of disorders (insomnia)
Disorders of natural physiological rest are classified depending on which specific stage or parameter of the process is impaired:
- Pre-somnic disorders — primary sleep-onset disorder (difficulty with induction).
- Intra-somnic disorders — impairment of depth and quality. Manifested as too superficial sleep, frequent causeless awakenings during the night, and anxious dreams.
- Post-somnic disorders — impairment of total duration. These include chronic sleep deprivation and early final awakening.
- Structural disorders — pathological alteration of the physiological ratio of slow (80%) and fast (20%) sleep.
Briefly: answers to topical questions
What stages does slow-wave sleep include?
Slow-wave sleep (Non-REM sleep) develops sequentially and includes four stages.
- Drowsiness stage — characterized by eye closure, easy awakening, and the presence of alpha waves on the EEG.
- Sleep spindles stage — occurs within 30 minutes after falling asleep; alpha waves form characteristic spindles.
- Theta wave stage — replaces spindles; high-amplitude slow theta waves are recorded, and awakening is difficult.
- Delta wave stage — a period of deep sleep with an increase in high-amplitude ultra-slow delta waves and the maximum awakening threshold.
What EEG changes are characteristic of paradoxical sleep?
Paradoxical sleep (REM sleep) is characterized by low-amplitude, high-frequency electrical brain activity resembling the waking state. The electroencephalogram records a $\beta$-rhythm with a frequency of 14–30 Hz. This phenomenon is called secondary desynchronization, as brain activity becomes fast again despite the person being in deep sleep.
Which receptors are the main pharmacological target for hypnotics?
Pharmacological targets for hypnotics, confirmed by sources, are:
- GABA-A receptors — zaleplon interacts with their benzodiazepine binding sites.
- $\omega_1$-benzodiazepine receptors — zolpidem is their selective agonist.
- $H_1$-histamine receptors — their blockade provides the hypnotic effect of diphenhydramine and doxylamine.
- Benzodiazepine receptors — flumazenil is their competitive antagonist.
Which specific drugs (INN) are used to treat pre-somnic disorders?
To treat pre-somnic disorders (sleep-onset disorders), the following are used:
- Benzodiazepine tranquilizers — diazepam, phenazepam, lorazepam, clonazepam.
- Non-benzodiazepine hypnotics (Z-drugs) — zopiclone, zolpidem (Zolpidem), zaleplon (Zaleplon).
What physiological parameters, besides eye movements, change during the REM sleep phase?
During the REM sleep phase (REM sleep), in addition to rapid eye movements, changes occur in electrical brain activity and muscle tone. The electroencephalogram records low-amplitude high-frequency activity ($\beta$-rhythm 14–30 Hz), which corresponds to secondary desynchronization. At the same time, motor output is completely blocked, which clinically manifests as physiological muscle atonia.
Insomnia classifications are easy to remember by Latin prefixes: pre-somnic (problem BEFORE sleep — trouble falling asleep), intra-somnic (problem WITHIN — frequent awakenings), post-somnic (problem AFTER — early awakening and sleep deprivation).
Class and exam questions
What is delta sleep?
This is the fourth, deepest stage of slow-wave sleep. It is characterized by the appearance of specific slow, high-amplitude $\delta$-waves on the EEG.
Which neurotransmitter is the main sleep inducer?
Serotonin is the key factor triggering the process of physiological sleep onset.
How often does the dreaming phase occur per night?
Episodes of fast-wave sleep (REM sleep), which are accompanied by dreams and rapid eye movements, cyclically repeat every 80–90 minutes.
What else to study on this topic
- Mechanism of action of hypnotic drugs
- The role of the GABAergic system in central nervous system inhibition
- The effect of melatonin on circadian rhythms
- EEG changes at different stages of slow-wave sleep
- Pharmacotherapy of pre-somnic and intra-somnic disorders
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