Sedative Hypnotics
• Sedative : dose that reduces excitement,
physical activity and calms the person.
• Hypnotic : dose that produces sleep that
resembling with normal sleep.
• Sleep - Phases
Non Rapid Eye Movement (NREM )
Rapid Eye Movement (REM )
Sedative Hypnotics
[Link] [Link]
Long acting:
Long acting: Phenobarbitone
Diazepam, Flurazepam
Nitrazepam Short acting:
Pentobarbitone
Short acting: Butobarbitone
Alprazolam, Triazolam, Ultra short acting:
Temazepam Thiopentone
Methohexitone
3. Non benzodizepines: Zolpidem,Zopiclone,Zaleplon
Benzodizepines: Commonly used
Wide safety / High therapeutic index
Mech. of action /(M.O.A) BZDs
Bind to GABAA receptor Cl Channel
Increase frequency of opening of Cl Channels
Increase Cl ion conductance
Membrane hyperpolarization and CNS depression
Pharmacological actions:
CNS: Sedation– Hypnotic– Anaesthesia- Coma
Reduce anxiety, Skeletal muscle relaxation
Anticonvulsant and Amnesia.
CVS: decrease B.P & H.R (higher dose)
Resp. System: depress respiration
Gastric gland: decrease nocturnal acid secretion
prevent stress induced ulcers.
PK: Given orally, intravenously (IV) and rectal (Children)
IM rarely used.
undergoes enterohepatic circulation (Diazepam)
cross placental barrier
(R.S depression & Hypotonia- Floppy Baby syndrome)
secreted in milk
A/E: Drowsiness, confusion, blurred vision, amnesia
Vertigo, Weakness, urine retention, dry mouth
sometimes paradoxical effects – anxiety
convulsions
irritability
Tolerance & Dependence: less with BZDs (Short term )
Uses:
[Link] : i) Transient (1-3 days) Environmental or
situational change
ii) Short term(3-21days) Emotional problem
Physical illness
iii) Chronic insomnia( >21 days) COPD
severe pain, GERD, CHF, Psychosis.
2. Antianxiety /anxiolytic effect :Act on limbic system and
relieve anxiety (at low dose)
3. Skeletal muscle relaxant : inhibit polysynaptic
reflexes at spinal and supra spinal level.
Useful in spinal injury, tetanus, cerebral palsy, and
sprain.
4. Preanaesthetic medication : Sedation, Hypnotic,
Anaesthesia, Reduce anxiety, Skeletal muscle
relaxation, Amnesia (Pt cant recall preoperative event)
5. Anticonvulsant : Diazepam used in status epileptics,
tetanus, febrile convulsions (IV)
Clonazepam used in the absence seizure
6. Gen. anaesthesia : Midazolam / Diazepam used to
maintained.
7. Diagnostic & minor operative procedures:
Endoscopies, before ECT, in Obstetrics
8. To control alcohol withdrawal symptoms : anxiety,
nausea, vomiting, palpitation etc.
[Link] sedation : pt is able to communicate &
co-operate during procedure.
10. Along with analgesics and antiulcer agents.
Barbiturates : derivatives of barbituric acid
low therapeutic index
M.O.A : Barbiturates
Bind to GABAA receptor Cl Channel
Prolong the duration of opening of Cl Channels
Increase Cl ion conductance
Membrane hyperpolarization and CNS depression
High dose : GABA mimetic effect, decrease Ca++ and
glutamate activity
Pharmacological actions:
CNS: Sedation– Hypnotic– Anaesthesia- Coma- death
Skeletal muscle relaxation, Anticonvulsant
CVS: decrease B.P & H.R (higher dose)
Resp. System: depress respiration (medullary paralysis)
GIT: decrease tone & motility
GUT : increase release of ADH (decrease urine output)
PK: Given orally, intravenously (IV)
hepatic microsomal enzyme inducers
cross placental barrier, secreted in milk.
A/E: Headache, Drowsiness, confusion, nausea,
Vomiting, vertigo, ataxia, hypotension.
Megaloblastic anaemia (on prolong use)
Precipitation of porphyria (Induce ALA synthase)
Hypersensivity reaction.
Physical & psychological dependence develops on
repeated use
Uses:
[Link] :not recommended (low therapeutic index)
2. Preanaesthetic medication : were used for sedation,
Hypnotic effect.
3. Gen. anaesthesia : Thiopentone or Methohexitone
used for induction of GA
4. Anticonvulsant : Phenobarbitone used in GTCS,
Status epileptics, eclampsia,
Febrile convulsions (IV)
[Link] jaundice of non haemolytic type &
Kernicterus : Phenobarbitone accelerate metabolism
of bilirubin (enzyme induction- glucuronyl transferase)
6. Diagnostic aid in psychiatry : low dose of thiopentone
facilitate verbal communication. (mainly in hysteria)
Acute barbiturate poisoning: rare
mostly accidental or suicidal
Symptoms: Resp. depression, HypoTN, CVS collapse,
Renal failure, and skin eruptions.
Treatment : maintain airway, breathing, circulation
Gastric lavage – after stomach wash
activated charcoal prevent absorption
Alkaline diuresis: IV Sod. Bicarbonate
(facilitate elimination of acidic drugs)
Haemodialysis & haemoperfusion
(through column of activated charcoal / other adsorbant )
Non BZDs
Bind to GABAA receptor Cl Channel
Facilitate GABA mediated neuronal inhibition
CNS depression
Used for short term treatment
Rapid & Short acting agents
Minimal A/E
Don’t produced dependence/withdrawal effects
Ramelteon: agonist of melatonin receptor
(MT1 & MT2)
reduces sleep latency period
no - rebound insomnia
withdrawal symptoms.
undergoes first pass metabolism.
half life: 2-5 hrs.
S/E : dizziness, drowsiness, ↓testosterone,
↑ prolactin level.
Buspirone: partial agonist of 5 HT1a receptors.
inhibit further release of serotonin.
Benzodizepines Barbiturates
• High therapeutic index • Low therapeutic index
• Commonly use • Restricted use
• Increase frequency of • Prolong duration of opening
opening Cl Channel Cl channel
• No GABA mimetic effect • GABA mimetic effect
• Don’t affect RS & CVS • Can affect
functions
• Low abuse liability • High abuse liability
• No enzyme induction • Enzyme inducers
property
• Antidote – Flumazenil • No antidote available in
Used in overdosage poisoning
