Hypnotics and sedatives

Presented by
T. Anila
M.Pharmacy
Reg:-19L81S0102
PHARMACOLOGY
RIPER, (AUTONOMOUS)
 INRODUCTION TO SLEEP CYCLE
• A lot happens in your body while you sleep.
• When you get sleep , you cycle between REM and non- REM
cycles.
• REM stands for rapid eye movement. During REM sleep,
your eyes move quickly in different directions. That doesn't
happen during non-REM sleep.
• First comes non-REM sleep, followed by a shorter period of
REM sleep, and then the cycle starts over again. Dreams
typically happen during REM sleep.
SLEEP CYCLE
Stages of sleep cycle
• Sedative-hypnotic drug products are a class of drugs used to
induce or maintain sleep.
• Reticular activating system (RAS) is responsible for
wakefulness. Sleep and wakefulness are dependent on the
release of neuro-humoral substances. Drugs that influence the
activity of any one of the neurotransmitters would affect sleep
process.
• Hypnotics: a drug which produce sleep resembling natural sleep.
• Sedatives: Drug that reduces excitement, calms the patient is
commonly used as anxiolytic.
• Sedatives in higher doses produce hypnosis.
• Hypnotics in higher doses produces General anaesthetics.
 SEDATIVES

• Drugs that have an inhibitory effect on the CNS that

reduce
 nervousness
 excitability
 irritability
• Sedative may be referred to as tranquilizers,
depressants, anxiolytics.
• Site of action is on the limbic system which
regulates thoughts and mental function.
 HYPNOTICS
• Calm or soothe the CNS to the point that they
cause sleep.
• Used in treatment of several insomnia.
• A sedative can become hypnotic if it is given
in large enough doses.
• Hypnotics in higher doses produce
anaesthesia.
• Site of action is on Midbrain and ascending RS
which maintain wakefulness.
Classification of hypnotics and sedatives:
• Barbiturates:
Long acting: Phenobarbitone, Pentobarbitone
Short acting: Butobarbitone , Methohexitone
Ultra short acting: Thiopentone
Benzodiazepines:
Hypnotic: Diazepam Flurazepam, Nitrazepam
Alprazepam, Triazolam.
Anti anxiety : Diazepam, Oxazepam, Lorazepam
Alprazolam, Chlordiazepoxide.
• Anticonvulsants:
Diazepam, Lorazepam, Clonazepam

NEWER NONBENZODIAZEPINES
HYPNOTICS
Zopiclone ,Zolpidem, Zaleplon
 Mechanism of action
Barbiturates/ benzodiazepines

Bind to GABAa receptor at different allosteric sites

Facilitates GABA actions

Barbiturates increases duration of action

&benzodiazepines increases frequency of opening of
Cl channel

Membrane Hyperpolarisation

CNS depression
Mechanism of action:
Pharmacokinetics of hypnotics and sedatives

• All barbiturates are weak acids.

• Lipid soluble
• Absorbed orally
• Distribute throughout the body
• Metabolized in the liver to inactive metabolites
• Cross placenta(pregnancy)
 Pharmacological actions
• CENTRAL NERVOUS SYSTEM: In dose-dependent
• Sedative
• Hypnotic
• Anesthesia in larger dose
• Anticonvulsant action
• Coma and death
• RESPIRATORY SYSTEM:
• Supress hypoxic and chemoreceptor response to CO2
• Larger doses leads to respiratory depression & death.
• CVS:
• Healthy patient: at low doses , they have
insignificant effects.
• Hypovolemicustates (decrease in intravascular
volume) ,CHF: normal dose may cause
cardiovascular collapse.
• Larger dose circulatory collapse due to
medullary vasomotar depression.
Dose Dependent Action:

Sedation Anesthesia Death

(sedative) (anaesthetic)

Sleep
Coma
(hypnotic)
 Therapeutic uses of Barbiturates:
• Sedative / hypnotic:
• Barbiturates have been used mild sedative to
relieve anxiety , nervous tension and insomnia.
• Phenobarbital used un long- term management
of tonic- clonic seizures.
• Hyperbilirubinemia and Kernicterus in the
neonates(increase glucouronyl transferase
activity)
Therauptic uses of benzodiazepines:
• Anti convulsant
• Several benzodiazepines have anti convulsant
activity.
• This effect partially, not completely, mediated α1-
GABAA receptors.
• Muscle relaxant:
• At higher doses the benzodiazepines relax spasticity of
skeletal muscle.
• All benzodiazepines have sedative and calming properties,
produce hypnosis at higher doses.
Adverse Effects:
• Barbiturates:
• Chronic use:
• metabolic tolerance occurs with phenobarbital .
• Abrupt with drawl from barbiturates may cause
tremors, anxiety, weakness, cardiac depression.
• Death may also occur from overdose.
• Contraindications:
• In patients with acute porphyria ( because of
increases heme synthesis)
Adverse effects:
• Benzodiazepines:
• Ataxia at higher doses.
• Cognitive impairment
• Benzodiazepines should be cautiously used in patient
• With liver disorder.
• Alcohol and other CNS depressants enhance sedative-
hypnotic effects in benzodiazepines.
• Administration in third-trimester results in “floppy-
infant syndrome”(low muscle tone).
Some common side effects of some include:

• Headache
• Nausea
• Short-term forgetfulness
• Rebound insomnia
• Dry mouth
• Hallucinations
• Dizziness
• Drowsiness
• Withdrawal symptoms (for example: anxiety or insomnia)
• Unpleasant taste
 Recent advances
• 5-HT ₂ₐ Receptor antagonists:
 5-hydroxytryptamine antagonists are
promising therapeutic agents for the treatment
of sleep maintenance insomnia.
Ex: Eplivanserin, Volinanserin.
• Orexin receptor antagonist.
Ex: Suvorexant, Elmorexant.