Download SEDATIVES / HYPNOTICS Barbiturates • Second choice as sedative

SEDATIVES / HYPNOTICS
Barbiturates
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Second choice as sedative – hypnotic
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Its members end with the suffix (barbital or barbitone)
Classification :
Long acting( 24-28 h): Phenobarbitone
 Intermediate (8-24h): Amylobarbitone
 Short-acting(3-8h):
o Pentobarbitone
o Secobarbitone
o Amobarbital
 Ultrashort acting (25 minutes): thiopental
Mechanism of Action
1. Facilitation of GABA action on the brain. increase the duration of the GABA gated channel opening
but in large dose, they can directly activating chloride channels. (not through BZD receptors).
2. depress excitatory neurotransmitter actions
3. Interfere with Na & K transport across cell membranes (reticular activating system inhibition).
Pharmacological actions
1 CNS depression:
In a dose-dependent fashion.
 Sedative
 Hypnotic
 Anesthesia in large dose
 Anticonvulsant action
 Coma and death.
2. Respiratory depression:
is dose –related.
 suppress hypoxic and chemoreceptor response to CO2
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Large doses respiratory depression & death.
3. CVS depressions
 Healthy patient: at low doses, they have
 insignificant effects.
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Hypovolemic states, CHF, normal doses
may cause cardiovascular collapse.
 Large dose  circulatory collapse due to
medullary vasomotor depression  direct
vasodilatation.
4. Enzyme induction.
CYT P-450 microsomal enzymes inducers (Tolerance - drug interaction).
Uses :
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Anticonvulsants: (Phenobarbitone)
tonic-clonic seizures, status epilepticus and febrile convulsion.
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Induction of anesthesia
o (thiopental, methohexital).
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Hypnotic (pentobarbital)
Dosage of Barbiturate:
 Phenobarbital: 15-30mg 2-3 times daily.
 Pentobarbital: 100-200mg daily.
Adverse effects:
1. Respiratory depression.
2. Hangover: residual sedation after awakening.
3. Tolerance
4. Withdrawal symptoms
5. Many drug interactions.
6. Allergic reaction: urticaria and skin rash.
Acute Toxicity of Barbiturates:
Hypoxia, cyanosis, hypothermia.
Respiratory, circulatory failure, coma, death.
Treatment of Toxicity:
 Emergency treatment by supporting respiration and circulation.
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Inhibiting further absorption by gastric lavage (if no coma) and promoting renal excretion by
forced alkaline diuresis and hemodialysis.
CNS stimulant drugs can be used such as analeptics.
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Tolerance
Acute tolerance develops virtually right away
Chronic tolerance seems first to develop to the depressant effects
Next to the antianxiety effects
Cross tolerance within benzodiazepines
Some cross tolerance to barbiturates and alcohol
Drug Interactions of Barbiturates:
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Barbituartes would decrease the serum levels and the effect of concurrently administered drugs
due to induction of liver microsomal enzymes.
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Concurrent use of barbiturates and the other CNS depressant drugs may lead to respiratory
depression.
Ⅲ.Nonbarbiturate sedative hypnotics
Chloral hydrate
 relatively safe hypnotic, inducing sleep in a half hour and lasting about 6h.
 used mainly in children and the elder, and the patients when failed to other drug.
 Chloral hydrate is a non-selective CNS depressant
 Withdrawl from drug causes disrupted sleep and intense nightmares
 Combination of chloral hydrate and alcohol can produce increased intoxication, stupor, and
amnesia
BUSPIRONE
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Chemically related to benzodiazepines
does not act at GABA receptors
Little cross-tolerance with alcohol, other depressants
Ot anti-convulsant or muscle relaxant
Affinity for 5-HT1A receptors and some DA receptors
Pharmacological actions complex
Anxiolytic effects develop slowly (weeks)
Does not have sedative effects
Used for generalized anxiety disorder (GAD)
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