.

1. Hypnotics
.

2. Hypnotics
•Hypnotics drugs use for insomnia
•Sleep is regulated by the hypnotic brain stem
system. Waking is included and maintained
by the ascending reticular formation of the
brainstem.

3. Phases of sleep
«Slow "-" synchronized "sleep - 75%
of the total sleep time.
Synchronous work of the cortex, a decrease in the secretion of
endocrine glands, body temperature, blood pressure, a predominance
of the vagal nerve tone, a decrease in the frequency of respiration and
heartbeat, a decrease in the tone of skeletal muscles.
«Fast "-" desynchronized "sleep -
25% of the total sleep time.
The presence of dreams, an increase in the tone of sympathetic NS,
metabolism, secretion of mediators, GCS, rapid eye movement,
increased blood pressure.

4. Hypnotics with non-narcotic type of action
Benzodiazepine receptor agonists
Benzodiazepine derivatives:
Nitrazepam
Flunitrazepam
Triazolam
Midazolam
Diazepam
Phenazepam
Preparations of other chemical groups:
Zopiclone, Zolpidem
Classification of hypnotics

5.  H1 blockers of histamine receptors:
Doxylamine
 Melatonin receptor agonists:
 Ramelteon
 Hypnotics with narcotic effect
 Derivatives of barbituric acid:
 Phenobarbital

6. • Have anti-anxiety (anxiolytic) action
Benzodiazepine derivatives
Benzodiazepine derivatives
Short
actions
Medium duration Long-
acting
Midazolam
T1 / 2 = 1.5-3.5 hours
Triazolam
T1 / 2 = 1.5 - 5 hours.
Nitrazepam
T1 / 2- 16-48 hours.
Oxazepam
T1 / 2 = 5-11 hours.
Flunitrazepam
T1 / 2> 20 hours.
Phenazepam
Diazepam
(seduxen, reium,
sibazon)

7.  Anti-anxiety, sedative - in small doses
 Hypnotic
 Decreased tone of skeletal muscles
 Anticonvulsant activity
 Potentiating the effects of anesthetics
Effects of Benzodiazepine
derivatives

8. Short - acting benzodiazepines
• Midazolam
• Has a pronounced hypnotic-narcotic effect,
therefore it is used in order to facilitate falling
asleep and in anesthesiology for
premedication, introduction to anesthesia and
its maintenance.

9. Benzodiazepines of medium
duration
• Nitrazepamum
• Sleep occurs in 30 to 40 minutes and lasts 6
to 8 hours.
• For the treatment of violations of the third
form of sleep

10. Benzodiazepines of long
duration
• Phenazepamum
• Highly active
tranquilizer
• For the treatment of the second
and the third form of sleep disturbance

11. Benzodiazepines of long
duration
• Diazepamum

12. Anxiolytics or Tranquilizers
Groups Preparations
1.Benzodiazepine receptor
agonists
Diazepam, Phenazepam,
Mezapam, Midazolam,
Triazolam
2.Serotonin receptor
Agonists
Buspirone
3. Substances of different
types of action
Mebicar, Amisyl

13. Tranquilizers
 Preparations with predominantly sedative action:
Phenazepam
Amisyl
 "Daytime":
 Mezapam
 Mebikar
Without significant sedative properties, which have
a stimulating effect

14.  Limbic system
 Hypothalamus
 Talamus
 Hypothalamus
 Reduce anxiety
 Anxiety
 Eliminate fear
 Reduce anxiety and aggression
Anti-anxiety action, sedative

15.  Stimulates benzodiazepine receptors
 Forms complexes with GABA receptors, forming
a chlorine channel.
 Increase the sensitivity of GABA receptors to
GABA
 Increased binding of GABA to alpha and beta
receptor subunits
 Opens the chlorine channel
 Increases the flow of chloride ions
 hyperpolarization
The mechanism of action
of benzodiazepines

16. Amber half-aldehyde
GABA
Glutamate
GABA
Benzodiazepines
ГДК
Cl-
Cl-
Plasma
membrane
Chlorine ion channel
The receptor on the postsynaptic membrane is
BD-GABA-Cl- - ionophore complex

17. Tranquilizers
Types of action on the body
Pronounced
Anxiolytic
(anti-anxiety)
Anticonvulsant
Miorelaxing
Hypno-sedative
Vegeto-correcting

18. Pharmacological effects:
 Anxiolytic action (relieve fear, anxiety, eliminate emotional
excitability)
 Sedative action
 Hypnotic action
(little influence on the structure of sleep)
 muscle relaxant effect
 Potentiates the effect of hypnotics, anesthetic agents
 Anticonvulsant action
 Amnestic effect
 A number of them has antiarrhythmic effect, dilates
coronary vessels, improve cerebral circulation.

19. USE
 Neurosis and psychological diseases with neurosis-like
disorders
 Situational and anxiety conditions (dental procedure)
 Therapeutic diseases with psychoemotional disorders
(angina pectoris, myocardial infarction, peptic ulcer)
 Phobic and anxiety disorders
 Neuritis

20. USE
 Insomnia
 Relief of epileptic status, withdrawal syndrome
 Premedication
Daytime
 Anxiety
 Stress in healthy people

21. Side effects:
 Aftereffect syndrome - lethargy, drowsiness,
impaired attention, reaction speed,
coordination of movements.
 Memory impairment
 muscle relaxant effect
 Violation of the menstrual cycle, decreased
sexual potency, skin rashes

22. Side effects:
 With long-term use - the development of drug
dependence (mental and physical).
 Withdrawal symptoms are less severe than with
physical dependence on barbiturates.
 teratogenic

23. Contraindications
 In the first 3 months of pregnancy
 It is not recommended that they be assigned to
transport workers

24. • 1) with difficulty falling asleep (against
the background of anxiety);
• 2) with sleep disturbance in general;
• 3) with short sleep in the elderly.
• The effect occurs in 20 - 30 minutes,
the duration of the hypnotic effect is 6-
8 hours. (midazolam 2-4 hours).
Benzodiazepines are prescribed :

25. Side effect of benzodiazepines
• Aftereffect syndrome:
• lethargy, muscle weakness, dizziness,
• Impaired coordination
• Difficulty concentrating
• Decreased mood and memory, drowsiness
• Tolerance (courses no more than 10 - 12 days)
• Drug dependence, withdrawal syndrome (for
short-acting drugs)

26. Hypnotics of other groups
• 2) Cyclopyrrolone derivatives:
• Imovan INN - Zopiclone
• Zolpidem
• The effect comes in 30 minutes and lasts 6-8 hours.
• practically does not affect the structure of sleep
• practically does not cause aftereffect syndrome
• practically does not cause the phenomenon of
"withdrawal"
• Does not form active metabolites
• Does not impair performance
• selective action
• Do not take continuously for more than 4 weeks,
because after 4 weeks may develop addiction, drug
addiction

27.  Dizziness
 Drowsiness
 Irritability
 Confusion of consciousness
 Tolerence, drug dependence (4 weeks)
Zopiclone
 Bitterness and dryness of the mouth
 Zolpidem
 hallucinations, ataxia
Preparations of another chemical
structure. Side effects (high doses)

28. Hypnotics other groups
• 1)
• Antihistamines of the first generation,
depressing the central nervous system
(diphenhydramine, diprazine, tavegil,
donormil)
• H1 histamine receptor blockers:
Doxylamine
•

29. Used to insomnia
Hypnotics other groups

30. Ramelteon
• This is a synthetic drug that accelerates the adaptation of
the organism to the change of time zones, the disturbance
of the sleep regime.
• The active substance - synthesized melatonin - is an
analogue of the natural hormone melatonin, which is
produced with the onset of the dark time of the day and
provides relaxation

31. Ramelteon
It is used as an adaptive tool for air travel, for insomnia, working
on night shifts.
More active than melatonin
Reduces time to fall asleep (30 minutes)
Does not cause drug dependence
Can be prescribed for a long time

32. Ramelteon
Side effect:
Allergic reactions
Morning sleepiness
Increased prolactin

33. Derivatives of barbituric acid
1. Phenobarbital (8 hours)
1) Low therapeutic range
(a dose of 5 to 10 times more than a hypnotics causes a deep
anesthesia with a dangerous respiratory depression;
2) affects the structure of sleep (suppresses the phase of "fast" sleep), a
the phenomenon of recoil ; with abrupt withdrawal of the drug, the
patient may have nightmares
3) Phenobarbital is an inducer of liver enzymes, so the hypnotic effect
decreases with repeated doses (addictive)
4) Causes sleep close to narcotic, cumulates

34. Derivatives of barbituric acid
• The hypnotic effect of phenobarbital occurs in
60 to 90 minutes!
T1 / 2 - 85 hours
• All barbiturates leave a prolonged and more
pronounced effect than in benzodiazepines aftereffect
• In doses of 1/2 - 1/3 hypnotic barbiturates have
a sedative effect

35.  Stimulates barbiturate receptors
 Forms complexes with GABA receptors,
forming a chlorine channel.
 Increase the sensitivity of GABA receptors to
GABA
 Increased binding of GABA to alpha and beta
receptor subunits
 Opens the chlorine channel
 Increases the flow of chloride ions
 hyperpolarization
mechanism of action

36. General contraindications to the use
of hypnotics
- Children under 15 years old
- Pregnancy
- Lactation
- With caution in sleep apnea

37.  What is used for insomnia associated with anxiety, a
sense of fear?
 What is used for insomnia if the patient works the
night shift
 What kind of hypnotic drugs practically does not
affect the structure of sleep
 With the abrupt cancellation of which sleeping pill,
the phenomenon of recoil is most clearly manifested.

75. History of Antiepileptic
Drug Therapy in the U.S.
• 1857 – bromides
• 1912 – phenobarbital (PB)
• 1937 – phenytoin (PHT)
• 1944 – trimethadione
• 1954 – primidone
• 1958 – ACTH
• 1960 – ethosuximide (ESM)
• 1963 – diazepam
• 1974 – carbamazepine (CBZ)
• 1975 – clonazepam (CZP)
• 1978 – valproate (VPA)
P-Slide 75
• 1993 – felbamate (FBM),
gabapentin (GBP)
• 1995 – lamotrigine (LTG)
• 1997 – topiramate (TPM),
tiagabine (TGB)
• 1999 – levetiracetam (LEV)
• 2000 – oxcarbazepine
(OXC), zonisamide
(ZNS)
• 2005 - pregabalin (PGB)
• 2008 – lacosamide (LCM),
rufinamide (RUF)
• 2009 – vigabatrin (VGB)
American Epilepsy Society 2011

105.  Uses • It is the most effective drug for CPS • First choice drug
with phenytoin for GTC and SPS . • Trigeminal and related
neuralgias - is the drug of choice. • Manic depressive illness
and acute mania - as an alternative to lithium
 ETHOSUXIMIDE •
 Inhibit T type Ca+2 current in thalamic neurons.
 • Adverse effects – GI intolerance, tiredness, mood changes,
agitation, headache, drowsiness and inability to concentrate
 • Uses – Only in ABSENCE SEIZURES but Use has now declined
as many consider valproic acid to be superior to it.

106.  Multiple mechanisms of action :
 • Phenytoin like frequency dependent prolongation of Na*
channel inactivation.
 • Attenuation of Ca2+ mediated 'T' current (ethosuximide like) •
Augmentation of release of inhibitory transmitter GABA by
inhibiting its degradation (by GABA-transaminase) & by
increasing its synthesis.
 Uses • Highly effective in absence seizure. • Alternative
/adjuvant drug for GTCS, SPS and CPS. • Myoclonic and atonic
seizures—control is often incomplete, but it is the drug of
choice. • Mania and bipolar illness: as alternative to lithium.
 Adverse effects • anorexia, vomiting, loose motions, heart burn
• Drowsiness, ataxia, tremors • Alopecia, curling of hair,
increased bleeding tendency • Fulminant hepatitis (very rare0 •
Pancreatitis • High incidence of PCOD in young girls •
Teraotogenic 22
VALPROIC ACID (Sodium Valproate)

107.  Blocks sodium as well as high voltage dependent calcium
channels
 Uses • Broad spectrum antiepileptic.
 • Refractory cases of partial seizures and GTCS
 • Absence and myoclonic or akinetic epilepsy .
 • Lennox-gastaut syndrome
 Adverse effects
 • sleepiness, dizziness, diplopia,ataxia and vomiting. • better
tolerated than carbamazepine or phenytoin. • Rash may be a
severe
LAMOTRIGINE

108.  GABAPENTIN • Enhances GABA release in brain. • does not act as
agonist at GABAA receptor.
 • Reduces seizure frequency in refractory partial seizures with or
without generalization.
 • Manic depressive illness and migraine
 • first line drug for pain - diabetic neuropathy and postherpetic
neuralgia,
 • Adverse effects - mild sedation, tiredness, dizziness and
unsteadiness.
 VIGABATRIN
 • Inhibitor of GABA-transaminase which degrades GABA
 • Effective in refractory epilepsy, specially partial seizures with or
without generalization.
 • Adverse effects- behavioral changes, depression and psychosis .
drowsiness, amnesia, visual field contraction, motor disturbances,
agitation in children.

109.  • Recently developed anticonvulsant -
potentiates GABA mediated neuronal
inhibition by depressing GABA transporter
GAT-1 which removes synaptically released
GABA into neurons & glial cells.
 • Uses – add on therapy of partial seizures
with or without secondary generalization.
 • Adverse effects- mild sedation,
nervousness, asthenia, amnesia & abdominal
pain.
TIAGABINE