SLEEP INDUCING DRUGS

1. SLEEP INDUCING DRUGS

2.  The duration and pattern of
sleep varies considerably
among individuals. Age has
an important effect on
quantity and depth of
sleep.
 It has been recognized that
sleep is an architectured
cyclic process. The different
phases of sleep and their
characteristics are—

3.  From lying down to falling asleep and occasional
nocturnal awakenings; constitutes 1–2% of sleep
time.
 Eye movements are irregular or slowly rolling.

4.  Eye movements are reduced but there may be bursts
of rolling.
 Neck muscles relax. Occupies 3–6% of sleep time.

5.  (unequivocal sleep) θ waves with interspersed
spindles, K complexes can be evoked on sensory
stimulation; little eye movement; subjects are easily
arousable. This comprises 40–50% of sleep time.
Stage 3 (deep sleep transition)
 Eye movements are few; subjects are not easily
arousable; comprises 5–8% of sleep time.

6.  (cerebral sleep) δ activity predominates in EEG, K
complexes cannot be evoked. Eyes are practically
fixed , subjects are difficult to arouse. Night terror
may occur at this time. It comprises 10–20% of sleep
time.
 During stage 2, 3 and 4 heart rate, BP and respiration
are steady and muscles are relaxed. Stages 3 and 4
together are called slow wave sleep (SWS).

7.  REM sleep (paradoxical sleep)
EEG has waves of all frequency, K
complexes cannot be elicited.
 There are marked, irregular and
darting eye movements; dreams
and nightmares occur, which may
be recalled if the subject is aroused.
 Heart rate and BP fluctuate;
respiration is irregular. Muscles are
fully relaxed, but irregular body
movements occur occasionally.

8.  A drug that subdues excitement and calms the subject
without inducing sleep, though drowsiness may be
produced.
 Sedation refers to decreased responsiveness to any
level of stimulation; is associated with some decrease
in motor activity and ideation.

9.  A drug that induces and/or maintains sleep, similar to
normal arousable sleep.
 This is not to be confused with ‘hypnosis’ meaning a
trans-like state in which the subject becomes passive
and highly suggestible.

10. Barbiturates
Long acting Short acting Ultra-short
acting
Phenobarbitone Butobarbitone
Pentobarbitone
Thiopentone

11. Benzodiazepines
Hypnotic Antianxiety Anticonvulsant
Diazepam
Flurazepam
Nitrazepam
Alprazolam
Temazepam
Triazolam
Diazepam
Chlordiazepoxide
Oxazepam
Lorazepam
Alprazolam
Diazepam
Lorazep
Clonazepamam
Clobazam

12.  Zopiclone
 Zolpidem
 Zaleplon

13.  Barbiturates are a group of drugs in the class
of drugs known as sedative-hypnotics, which
generally describes their sleep-inducing and
anxiety-decreasing effects.

14.  Barbiturates are general depressants for all
excitable cells, the CNS is most sensitive
where the effect is almost global, but certain
areas are more susceptible.
 CNS Barbiturates produce dose-dependent
 effects:
sedation → sleep → anaesthesia → coma.

15.  Hypnotic dose (100–200 mg of a short acting
barbiturate) shortens the time taken to fall asleep and
increases sleep duration.
 The sleep is arousable, but the subject may feel
confused and unsteady if waken early. Night
awakenings are reduced.
 REM and stage 3, 4 sleep are decreased; REM-
NREM sleep cycle is disrupted. The effects on sleep
become progressively less marked if the drug is taken
every night consecutively

16.  Sedative dose (smaller dose of a longer acting
barbiturate) given at daytime can produce
drowsiness, reduction in anxiety and
excitability
 Barbiturates can impair learning, short-term
memory and judgement. Barbiturates have
anticonvulsant property

17.  Barbiturates appear to act primarily at the GABA :
BZD receptor–Cl¯ channel complex and potentiate
GABA ergic inhibition by increasing the lifetime of
Cl¯ channel opening induced by GABA.
 At high concentrations, barbiturates directly increase
Cl¯ conductance and inhibit Ca2+ dependent release
of neurotransmitters. In addition they depress
glutamate induced neuronal depolarization through
AMPA receptors(is a non-NMDA-type ionotropic
transmembrane receptor for glutamate that mediates
fast synaptic transmission in the central nervous
system (CNS).)

18.  Respiration is depressed by relatively higher doses.
hypercapneic and hypoxic oocurs.
 CVS Hypnotic doses of barbiturates produce a slight
decrease in BP and heart rate, Reflex tachycardia can
occur, though pressor reflexes are depressed.
 Even the dose producing cardiac arrest is about 3 times
larger than that causing respiratory failure.
 Skeletal muscle- Hypnotic doses have little effect but
anaesthetic doses reduce muscle contraction by
depressing excitability of neuromuscular junction.

19.  Smooth muscles Tone and motility of bowel is
decreased slightly by hypnotic doses; more
profoundly during intoxication. Action on bronchial,
ureteric, vesical and uterine muscles is not
significant.
 Kidney Barbiturates tend to reduce urine flow by
decreasing BP and increasing ADH release. Oliguria
attends barbiturate intoxication.

20.  Phenobarbital, the longest-acting barbiturate,
is used for its anticonvulsant and sedative-
hypnotic properties in the management of all
seizure disorders except absence (petit mal)

21.  Phenobarbital acts on GABAa receptors, increasing
synaptic inhibition. This has the effect of elevating
seizure threshold and reducing the spread of seizure
activity from a seizure focus.
 Phenobarbital may also inhibit calcium channels,
resulting in a decrease in excitatory transmitter
release. The sedative-hypnotic effects of
phenobarbital are likely the result of its effect on the
polysynaptic midbrain reticular formation, which
controls CNS arousal.

22.  Central nervous system effects,
such as dizziness, nystagmus
and ataxia, are also common.
 In elderly patients, it may cause
excitement and confusion,
while in children, it may result
in paradoxical hyperactivity.
 Another rare side effect is
amelogenesis imperfecta

23.  Hypersensitivity to any barbiturates
 Prior dependence on barbiturates
 Severe respiratory insufficiency
 Hyperkinesia in children

24.  Butobarbital (BAN), also called
butobarbitone or butethal, Soneryl, and
Neonal, is a hypnotic drug which is a
barbiturate derivative.
 Butobarital is a barbiturate and is used as a hypnotic.
Although it is no longer recommended due to the risk
of dependence, tolerance and adverse effects, its
continued use may be necessary in severe intractable
insomnia in patients already on it

25.  Oral
 Severe intractable insomnia
 Adult: 100-200 mg at bedtime.

26.  Children, young adults, elderly and debilitated
patients.
 Patients with depression or with a history of drug or
alcohol abuse or addiction. Insomnia caused by pain.
 Acute porphyria.
 Severe hepatic impairment. History of CNS
depression or coma, pulmonary insufficiency and
sleep apnoea.
 Pregnancy & lactation.

27.  Drowsiness
 Ataxia
 paradoxical excitement
 confusion
 headache and CNS depression
 respiratory depression
 GI disorders
 hepatitis
 Fever megaloblastic anaemia.
Potentially Fatal: Erythema multiforme; exfoliative
dermatitis.

28.  Chlordiazepoxide and diazepam were
introduced around 1960 as antianxiety drugs.

29. Site and mechanism of action
 Benzodiazepines act preferentially on
midbrain ascending reticular formation
(which maintains wakefulness) and on limbic
system (thought and mental functions).
Muscle relaxation is produced by a primary
medullary site of action and ataxia is due to
action on cerebellum.

30.  BZDs act by enhancing presynaptic/postsynaptic
inhibition through a specific BZD receptor which
is an integral part of the GABAA receptor–Cl¯
channel complex.

31.  The most common side-effects of benzodiazepines
are related to their sedating and muscle-relaxing
action.
 drowsiness, dizziness, and decreased alertness and
concentration.
 Lack of coordination may result in falls and injuries.
 Hypotension and suppressed breathing.
 changes in appetite, blurred vision, confusion,
euphoria, depersonalization and nightmares
 irritability and suicidal behavior sometimes occur

32.  Pregnancy-
 risk of cleft palate.
 The symptoms include tremors, hypertonia,
hyperreflexia, hyperactivity, and vomiting and may
last for up to three to six months.
 Elderly-
 Effects such as memory problems
 daytime sedation
 impaired motor coordination
 and increased risk of motor vehicle accidents and
falls
 and an increased risk of hip fractures.

33. Diazepam, a benzodiazepine, generates the same active
metabolite as chlordiazepoxide and clorazepate.
Diazepam appears to act on parts of the limbic system,
the thalamus and hypothalamus, and induces calming
effects.
VALIUM 2, 5, 10 mg tab., 10 mg/2 ml inj.
CALMPOSE 5, 10 mg tab, 2 mg/5 ml syr, 10 mg/2 ml
inj.

34.  Benzodiazepines bind nonspecifically to
benzodiazepine receptors which mediate sleep,
affects muscle relaxation, anticonvulsant activity,
motor coordination, and memory.
 As benzodiazepine receptors are thought to be
coupled to gamma-aminobutyric acid-A (GABAA)
receptors, this enhances the effects of GABA by
increasing GABA affinity for the GABA receptor.
Binding of GABA to the site opens the chloride
channel, resulting in a hyperpolarized cell membrane
that prevents further excitation of the cell.

35.  It Produces an active metabolite which has a long t½,
residual effects are likely next morning; cumulation
occurs on daily ingestion peaking after 3–5 days;
suitable for patients who have frequent nocturnal
awakenings.
 NINDRAL, FLURAZ 15 mg cap.

36.  Nitrazepam is a type of benzodiazepine drug. It is
a powerful hypnotic drug which possesses strong
sedative, anxiolytic, amnestic, anticonvulsant, and
skeletal muscle relaxant properties. Nitrazepam
shortens the time required to fall asleep and
lengthens the duration of sleep. It is also useful
for the management of myoclonic seizures.
 SEDAMON, HYPNOTEX, NITRAVET 5 mg tab.,
5, 10 mg cap.

37.  Nitrazepam belongs to a group of medicines called
benzodiazepines. It acts on benzodiazepine receptors
in the brain which are associated with the GABA
receptors causing an enhanced binding of GABA
(gamma amino butyric acid) to GABAA receptors.
GABA is a major inhibitory neurotransmitter in the
brain, involved in inducing sleepiness, muscular
relaxation and control of anxiety and fits, and slows
down the central nervous system.

38.  The anticonvulsant properties of nitrazepam and
other benzodiazepines may be in part or entirely due
to binding to voltage-dependent sodium channels
rather than benzodiazepine receptors. Sustained
repetitive firing seems to be limited by
benzodiazepines effect of slowing recovery of
sodium channels from inactivation

39.  Alprazolam, a benzodiazepine, is used to treat panic
disorder and anxiety disorder. Unlike chlordiazepoxide,
clorazepate, and prazepam, alprazolam has a shorter
half-life and metabolites with minimal activity.
DOSAGE
 0.25 to 0.5 mg orally administered 3 times a day
Maximum dose: 4 mg orally administered in divided
doses

40.  It is an intermediate acting BZD.
 Absorption is slow in case of tablet but fast when
used in soft gelatin capsule. Good for sleep onset
difficulty, free of residual effects. Accumulation can
occur on daily ingestion.
DOSAGE
 7.5 to 30 mg orally once a day at bedtime
-In transient insomnia, a 7.5 mg dose may be
sufficient to improve sleep latency.
-In elderly or debilitated patients, therapy should
be initiated at 7.5 mg until individual responses are
determined.

41.  Temazepam produces CNS
depression at limbic, thalamic,
and hypothalamic levels of the
CNS. Temazepam increases the
affinity of the neurotransmitter
gamma-aminobutyric acid
(GABA) for GABA receptors by
binding to benzodiazepine
receptors. Results are sedation,
hypnosis, skeletal muscle
relaxation, anticonvulsant activity,
and anxiolytic action.

42.  Chlordiazepoxide-
 Chlordiazepoxide has antianxiety, sedative,
appetite-stimulating and weak analgesic
actions. The drug seems to block EEG
arousal from stimulation in the brain stem
reticular formation. The drug has been
studied extensively in many species of
animals and these studies are suggestive of
action on the limbic system of the brain,
which recent evidence indicates is involved
in emotional responses.

43.  Mild to moderate anxiety: 5 or 10 mg orally, 3 or 4
times per day
Severe anxiety: 20 or 25 mg orally, 3 or 4 times per
day

44.  Chlordiazepoxide binds to stereospecific
benzodiazepine (BZD) binding sites on GABA
receptor complexes at several sites within the central
nervous system, including the limbic system and
reticular formation. This results in an increased
binding of the inhibitory neurotransmitter GABA to
the GABA receptor.
 BZDs, therefore, enhance GABA-mediated chloride
influx through GABA receptor channels, causing
membrane hyperpolarization. The net neuro-
inhibitory effects result in the observed sedative,
hypnotic, anxiolytic, and muscle relaxant properties

45.  Oxazepam is believed to stimulate GABA receptors
in the ascending reticular activating system. Since
GABA is inhibitory, receptor stimulation increases
inhibition and blocks both cortical and limbic arousal
following stimulation of the brain stem reticular
formation.
 DOSAGE
 10 to 15 mg, 3 or 4 times daily

46.  Similar to other benzodiazepines, oxazepam exerts its
anxiolytic effects by potentiating the effect of
gamma-aminobutyric acid (GABA) on GABA-A
receptors through a cooperative mechanism of action.
 Benzodiazepine binding increases chloride
conductance in the presence of GABA by increasing
the frequency at which the channel opens. In contrast,
barbiturates increase chloride conductance in the
presence of GABA by prolonging the time in which
the channel remains open.

47.  The α2 subunit of the α2β3γ2 receptor complex is
thought to mediate anxiolytic effects while the α1
subunit of the α1β2γ2 receptor complex is thought to
mediate sedative, anticonvulsant and anterograde
amnesia effects

48.  Lorazepam, a benzodiazepine not transformed to
active metabolites, is used to treat anxiety, status
epilepticus, and for sedation induction and
anterograde amnesia.
 DOSAGE
 Initial dose: 2 to 3 mg orally per day administered 2
to 3 times per day
Maintenance dose: 1 to 2 mg orally 2 to 3 times a day
Parenteral:
IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

49.  Clonazepamam
 Clonazepam, a benzodiazepine, is used primarily as
an anticonvulsant in the treatment of absence
seizures, petit mal variant seizures akinetic and
myoclonic seizures, and nocturnal myoclonus

50.  1.5 mg orally per day divided into 3 doses; this may be
increased in increments of 0.5 mg to 1 mg every 3 days
until seizures are adequately controlled or until side
effects preclude any further increase.
Maximum dose: 20 mg orally per day

51.  Zopiclone
This newer cyclopyrrolone hypnotic is an agonist at a
subtype of BZD receptor involved in the hypnotic
action. The effect on sleep resemble those of BZDs,
but it does not alter REM sleep and tends to prolong
stages 3 and 4.
DOSAGE
 ZOPITRAN, ZOPICON, ZOLIUM, 7.5 mg tab, one
tab at bedtime for not more than 2–4 weeks (elderly
3.75 mg).

52.  Zopiclone exerts its action by binding on the
benzodiazepine receptor complex and
modulation of the GABABZ receptor chloride
channel macromolecular complex.

53.  Zolpidem is a sedative or hypnotic agent
 zolpidem in vitro binds the (alpha1) receptor
preferentially. The (alpha1) receptor is found
primarily on the Lamina IV of the sensorimotor
cortical regions, substantia nigra (pars reticulata),
cerebellum molecular layer, olfactory bulb, ventral
thalamic complex, pons, inferior colliculus, and
globus pallidus.
 DOSAGE
 NITREST, ZOLDEM, DEM 5, 10 mg tabs.

54.  This is the shortest acting of the newer non-BZD
hypnotics
 It interacts with the gamma-aminobutyric acid-
benzodiazepine (GABABZ) receptor complex.
Subunit modulation of the GABABZ receptor
chloride channel macromolecular complex is
hypothesized to be responsible for some of the
pharmacological properties of benzodiazepines,
which include sedative, anxiolytic, muscle relaxant,
and anticonvulsive effects in animal models.
 DOSAGE
 Dose: 5–10 mg (max 20 mg) at bed time.
 ZAPLON, ZALEP, ZASO 5, 10 mg tabs.

55.  Do not mix intravenous drugs in solution with any
other drugs to avoid potential drug-drug interactions.
 Taper dose as ordered because abrupt withdrawal can
precipitate seizure attacks.
 Provide comfort measures (e.g. small, frequent meals,
access to bathroom facilities, orientation, etc.) to help
patient tolerate drug effects Provide safety measures
(e.g. adequate lighting, raised side rails, etc.) to
prevent injuries.
 Educate client on drug therapy to promote
compliance.

56.  Monitor patient response to therapy (e.g. controlled
anxiety, sleep, etc).
 Monitor for adverse effects (e.g. hypotension,
dependence, hepatorenal dysfunction, etc).
 Evaluate patient understanding on drug therapy by
asking patient to name the drug, its indication, and
adverse effects to watch for.
 Monitor patient compliance to drug therapy.

57.  SLEEP
 CLASSIFICATION
 TYPES
 NURSES RESPONSIBILITY
 EVALUATION
 SUMMARY