Pharmacology sedative hypnotics

1. INTERNATIONAL MEDICAL SCHOOL
ALMATY

2. KHUSHBU JAN
GROUP-327
WEEK-7
Sedative-Hypnotics

3. Sleeping pills
(hypnotics)
A group of psychotropic medications used
to facilitate the onset of sleep and ensure
its sufficient depth and duration.

4. • Sleep - a physiological state characterized by
the absence of conscious mental activity and
a significant decrease in reactions to external
stimuli.
• Basic sleep phases:
❖Slow sleep (synonyms: slow-wave,
synchronized, orthodox)
❖Fast sleep (synonyms: fast-wave, paradoxical
sleep, rapid eye movement phase or-REM-
sleep, REM-sleep)

5. Phase slow-wave sleep
• Stage I "nap"
⮚ On the EEG - the disappearance and flattening of the alpha
rhythm, the appearance of low-amplitude slow theta waves.
⮚ Clinically – decreased muscle activity, respiratory rate and pulse,
decreased temperature, may be slow eye movements
• Stage II (shallow or light sleep) 45-55 % of total sleep time
⮚ On the EEG-theta waves dominate, "sleep spindles" appear.
• Stages III (5-8 % of total sleep time) and IV (10-15 % of total
sleep time) (deep sleep or delta sleep)
⮚ On the EEG , it is characterized by the presence of high-
amplitude delta waves, stage 3-delta waves occupy less than 50
% and stage 4 - if the deltaactivity is more than 50 %.
⮚ Clinically, the eyeballs are immobile, the muscle tone is
preserved, the muscles of the submandibular region are tense.

6. Phase slow-wave sleep
• 75-80% of total sleep time
• Functions:
⮚restoration of brain homeostasis and energy
consumption (synthesis of phosphatergic compounds,
hormones, proteins and nucleic acids)
⮚optimization of regulation of internal organs ' activity
⮚anchoring lucid memories

7. REM sleep phase
• Desynchronization response to EEG (rapid
fluctuations in electrical activity close to beta waves)
• Fast eye movements
• Drop in muscle tone
• Intensification of vegetative reactions, increased
hormonal activity ("vegetative storms")
• 20-25 % of total sleep time
• Functions: information processing, psychological
protection, forming a future behavior program,
sorting information

8. Sleep structure
• Cycle (a sleep segment that includes all consecutive
phases) of 70-100 minutes
• 4-6 full cycles (6-8hours)
• By the end of sleep, the duration of slow-wave sleep
decreases, while the proportion of REM sleep increases.
• As you get older, the duration of sleep decreases, and the
proportion of slow-wave sleep increases.
• Slow-wave sleep deficits - feeling of chronic fatigue,
decreased mental and physical performance (asthenic
syndrome)
• Paradoxical Sleep Deficit - increased excitability, violation
of the behavior control system (short temper, irritability,
impulsivity)

9. Causes of sleep disorders
• Physiological factors - violation of normal biorhythm (night
duty, flight to another time zone)
• Psychological issues - increased anxiety, stressful situations,
positive or negative emotions, intense mental activity during
the day, changes in the sleep environment, anxiety about
falling asleep
• Pathological conditions - symptoms of neurological, somatic
and mental illnesses
• Pharmacological services —use of drugs that increase the
excitability of the central nervous system

10. • Somatic diseases
⮚ Pain (chronic pain syndromes)
⮚ Respiratory disorders (chronic cough, paroxysmal nocturnal
dyspnea)
⮚ Nocturnal angina
⮚ Hyperthyroidism
⮚ Esophageal reflux, diarrhea, and other digestive disorders
⮚ Nocturia
• Mental illnesses
⮚ Depression
⮚ Mania
⮚ Anxiety disorders

11. • Drug and alcohol-related insomnia
⮚ Chronic alcoholism
⮚ Drinking alcohol before going to bed
⮚ Use of caffeine and other psychostimulants
⮚ Stopping taking alcohol, sedatives, or drugs
⮚ Discontinuation of sleeping pills
⮚ Akathisia caused by neuroleptics

12. Types of sleep disorders.
• Presomnic services – the process of falling asleep
is disrupted
• Intrasomics services - shallow sleep, insufficient
depth of sleep and frequent awakenings, feeling
of incessant mental activity, amnesia of sleep
periods
• Post-Somnicheskie sites — early awakening,
with the inability to resume sleep

13. Requirements for the ideal sleeping pill.
• The action should occur quickly (rapid entry into the
bloodstream and the place of action).
• It should selectively bind to the receptor and cause only a
hypnotic effect.
• It should cause a sufficiently deep and prolonged sleep, without
disturbing its structure.
• It should have a sufficient breadth of therapeutic action
• It should not cause a residual sedative effect on the next day
(have a rate of elimination that ensures the necessary sleep
time and no aftereffect on awakening)
• It should not cause addiction, mental and physical dependence.

14. Classification of sleeping pills.
• Sleeping pills with a non-narcotic type of action.
⮚ Benzodiazepine receptor agonists.
1. Benzodiazepine derivatives.
Nitrazepam (Radedorm, Eunoctin), Flunitrozepam
(Rohypnol), Triazolam (Halcyon), Midazolam (Dormicum).
2. Preparations of a different chemical structure (derivatives
of cyclopyrrolones and imidazopyridines). Zopiclone
(Imovan, Piclodorm), Zolpidem (Ivadal, Sanval).
⮚ H1 – histamine receptor blockers.
Diphenhydramine (Diphenhydramine), Doxylamine
(Donormil)

15. ⮚Synthetic analogs of melatonin
Vita-Melatonnin, Melaxen, Circadin
⮚Melatonin receptor agonists
Ramelteon

16. • Sleeping pills with a narcotic type of action.
Barbituric acid derivatives (barbiturates).
Phenobarbital (Luminal, Nembutal), Amobarbital
(Amital)
Aliphatic compounds.
Chloral hydrate.
• Combined medications.
Reladorm (cyclobarbital+diazepam)

17. Classification of sleeping pills by duration of
action
• Short-acting (1-5 hours)
⮚Triazolam, Midazolam, Zopiclone, Zolpidem
• Average duration of action
(5-8 hours)
⮚Temazepam, Chloral Hydrate
• Long-acting (more than 8 hours)
⮚Phenobarbital, Flunitrazepam, Nitrazepam,
Doxylamine.

18. Classification of sleeping pills
• First-generation drugs – barbiturates, bromureids, and
chloral hydrate.
• Second-generation drugs – H1–histamine receptor
blockers, benzodiazepine derivatives.
• Third-generation drugs - derivatives of cyclopyrrolones and
imidazopyridines, melatonin preparations.

19. Barbiturates.
• The first sleeping pill barbital (Veronal) released in 1903.
• Barbiturates were widely used in clinical practice until the
60s of the 20th century.
• Decline in use (high frequency of drug addiction, high risk
of overdose and death, occurrence of benzodiazepines)
• Currently excluded from the WHO list of essential
medicines
• Main mechanism of action - interaction with a region of
the GABA-receptor complex, increased sensitivity to the
mediator and increased duration of the activated state of
the chlorine channels associated with this receptor
complex, hyperpolarization of neuronal membranes.

20. Classification of barbiturates according to the
rate of onset of the effect and its duration.
• long-acting barbiturates (phenobarbital,
benzobarbital)
• average duration of action (barbamyl,
ethaminal-sodium, cyclobarbital)
• ultra-short-acting (hexobarbital (hexenal),
thiopental-sodium).

21. Clinical effects of barbiturates
• Psychosedative effect, muscle relaxation (small doses)
• Violation of coordination of movements, articulation,
slowing down of reflexes.
• Hypnotic effect (deep pseudo-healthy sleep ("black and
empty oblivion") they disrupt the normal structure of sleep,
inhibiting the REM sleep phase, and increase the threshold
of sensitivity to external and internal stimuli).
• Depression of the vital centers of the medulla oblongata
(respiratory depression, cardiac activity) - small therapeutic
range of action-risk of overdose.
• Anticonvulsant effect
• Stimulate microsomal oxidation in the liver (cytochrome
P450 inducers) acceleration of biotransformation of other
drugs.

22. Clinical use of barbiturates.
• Epileptology (anticonvulsants) Phenobarbital,
Benzobarbital
• Anesthesiology (premedication, anesthesia
products) Thiopental-sodium, Hexenal
• As part of complex sleeping pills and sedatives (in
small doses) Reladorm, Valokardin
• Sleeping pills
Nembutal, Amital

23. Side effects of barbiturates.
• Pronounced daytime aftereffect, due to the long
elimination period of the drug (T1 / 2 20-40 hours)
• Psychoemotional disorders due to the suppression of REM
sleep
• The occurrence of severe physical and mental
dependence.
• Violation of hematopoiesis
• Paradoxical reactions

24. Chloral Hydrate
• Hypnotic aliphatic series of medium duration of action
(6-8 hours), rapid onset of effect (10 minutes), low
breadth of therapeutic action
• Hypnotic, analgesic, anticonvulsant effect
• Indications: relief of mental arousal, sedation for pain
syndrome, anticonvulsant for spasmophilia, tetanus,
eclampsia
• Side effects: irritant effect on the mucous membranes,
cardiotoxic and hepatotoxic effects of metabolites,
lowering blood pressure, vomiting

25. Benzodiazepines.
• Short-acting (TS 1-8h)
⮚ Brotisolam (Lendormin),Triazolam (Halcyon), Midazolam
(Dormicum, Floridal)
• Average duration of action
(TS 5-15 h)
⮚ Nitrazepam (Radedorm, Berlidorm, Moghadon), Temazepam
• Long-acting (TS 20-50 hours)
⮚ Flunitrazepam (Rohypnol), Flurazepam
Effects on sleep phases: suppression of REM sleep, prolongation of
intervals between paradoxical phases, prolongation of stage 2 slow-
wave sleep, and shortening of stage 1, 3, and 4 slow-wave sleep

26. Antihistamines
• Diphenhydramine (Diphenhydramine),
Doxylamine (Donormil)
• Long-acting drugs (more than 8 hours)
• Cause a strong "aftereffect" (headaches,
drowsiness in the morning)
• They have holinoblokiruyushchy properties
• No dependency formation even with prolonged
use
• Effects on sleep phases: inhibition of REM sleep

27. Third-generation sleeping pills.
❖ Zopiclone (Imovan), Zolpidem (Ivadal)
• Mechanism of action – atypical selective action on central
benzodiazepine receptors, leading to hyperfunction of
hypnogenic brain structures.
• They are rapidly absorbed from the gastrointestinal tract,
peak plasma concentrations are noted in 1.5-2 hours, the
hypnotic effect develops within 30 minutes after ingestion,
and do not form active metabolites.
• TS 2-5 h - fast and short-acting sleeping pills.
• They do not have a muscle relaxant and residual sedative
effect, do not affect the structure of sleep, and have a low
probability of forming dependence and developing
tolerance.

28. ❖Synthetic melatonin analogs and
melatonin receptor agonists
▪ Mechanism of action: effects on melatonin
receptors regulating the sleep-wake cycle
▪ Shorten the latent period of sleep
▪ Increase your total sleep time
▪ Restore the natural circadian cycle
▪ Do not affect the structure of sleep
▪ Long-term use does not lead to the
development of addiction and withdrawal
syndrome

29. Sedatives
• Drugs that have a general calming effect
by reducing the excitability of the central
nervous system (from Lat. sedatio -
calming down).
• Main effect: reduced response to various
external stimuli and some reduction in
mental activity
• They do not have selective anxiolytic,
muscle relaxant and antipsychotic effects.

30. Classification of sedatives.
• Preparations based on plant extracts – tinctures of
valerian, motherwort, peony, passionflower
• Bromides – sodium bromide, potassium bromide
• Barbiturates in small doses (1/5 of sleeping pills)
Phenobarbital, ethaminal-sodium
• Combined medications – bellaspon (phenobarbital,
belladonna alkaloids, ergotamine), valokardin
(phenobarbital, ethylbromisovlerianate, peppermint
oil, hop oil), novo-passit (complex of plant extracts)

31. Indications for use of sedatives
• Stressful situations
• Mild neurosis with vegetative disorders and
neurovegetative symptoms
• Mild (presomnic)sleep disorders
• Psychosomatic diseases
Side effects - allergic reactions

32. Basic principles of sleep disorder therapy.
• Drugs should be prescribed only after the following general
measures::
❖ It is recommended to stop taking alcohol or
psychostimulants, such as caffeine, and stop taking
medications that are not prescribed by a doctor or in
excessive doses.
❖ Compliance with the daily routine (the patient should not
sleep during the day).
❖ The bedroom should be quite dark and quiet.
❖ You should not be overly concerned about sleep, as this can
increase insomnia.
• A" step-by-step " approach - switch to strong drugs only if
the milder ones are ineffective.

33. Contraindications and special instructions
• Pregnancy and lactation
• Children under 15 years of age
• During treatment, you should refrain from using
alcohol and other CNS inhibitors
• Avoid potentially dangerous activities that require
increased attention and quick response (driving a
car).
• Elderly patients, patients with hepatic or renal
insufficiency start taking sleeping pills with half
doses