sedative-hypnotic drugs sedative-hypnotic drugs. a sedative drug decreases activity, moderates...
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Sedative-HypnoticSedative-Hypnotic Drugs Drugs
A A sedativesedative drug decreases activity, drug decreases activity, moderates excitement and calms the moderates excitement and calms the recipientrecipient
A A hypnotichypnotic drug produces drowsiness drug produces drowsiness and facilitates the onset and maintenance and facilitates the onset and maintenance of a state of sleepof a state of sleep
Sedative (Anxiolytic)Sedative (Anxiolytic)
Exert a calming effect,Exert a calming effect,
Reduce tension, nervousness,Reduce tension, nervousness, fear, and apprehension,fear, and apprehension,
little or no effect on motor or little or no effect on motor or mental function.mental function.
HypnoticsHypnotics
Produce state of drowsiness,Produce state of drowsiness,
promote onset and maintenance of sleep,promote onset and maintenance of sleep,
Patient can be awakened readily.Patient can be awakened readily.
Drug ClassificationDrug Classification
BarbituratesBarbiturates
BenzodiazepinesBenzodiazepines
Miscellaneous agentsMiscellaneous agents
BarbituratesBarbiturates(duration of action)(duration of action)
Ultra Ultra Short action Short action (8-10 h)(8-10 h) ThiopentalThiopental
Short action Short action (10-40 h)(10-40 h) Amobarbital, Secobarbital, pentobarbital Amobarbital, Secobarbital, pentobarbital
Intermediate action Intermediate action (35-50 h)(35-50 h) ButabarbitalButabarbital
Long action Long action (80-120 h)(80-120 h) Phenobarbital, Phenobarbital,
BenzodiazepinesBenzodiazepines(duration of action)(duration of action)
Ultra Short action Ultra Short action (4-6 h)(4-6 h) Triazolam, MidazolamTriazolam, Midazolam
Short action Short action (12-18 h)(12-18 h) Lorazepam, Oxazepam, Temazepam, LormetazepamLorazepam, Oxazepam, Temazepam, Lormetazepam
Intermediate action Intermediate action (24h)(24h) Alperazolam, NitrazepamAlperazolam, Nitrazepam
Long action Long action (24-48 h)(24-48 h) Diazepam, Chlordiazepoxide, Florazepam, ClonazepamDiazepam, Chlordiazepoxide, Florazepam, Clonazepam
PharmacodynamicsPharmacodynamics
Both enhance action of GABA by binding to Both enhance action of GABA by binding to different site ofdifferent site of GABA GABAA A receptor/chloride channelreceptor/chloride channel Barbiturates are less specific than Benzodiazepines.Barbiturates are less specific than Benzodiazepines.
Barbiturates increase the Barbiturates increase the durationduration but but Benzodiazepines increase the Benzodiazepines increase the frequencyfrequency of GABA- of GABA- mediated chloride ion channel opening.mediated chloride ion channel opening.
PharmacodynamicsPharmacodynamics
Barbiturates Block the excitatory transmitter Barbiturates Block the excitatory transmitter glutamic acid.glutamic acid.
Barbiturates At high concentration block the Barbiturates At high concentration block the sodium channels.sodium channels.
GABAGABAAA receptorsreceptors
PharmacokineticsPharmacokinetics
AbsorptionAbsorption Oral absorption of Benzodiazepines depend on lipophilicity Oral absorption of Benzodiazepines depend on lipophilicity (Triazolam extremely rapid and Diazepam more rapid than others) (Triazolam extremely rapid and Diazepam more rapid than others)
Barbiturates are usually absorbed very rapidly Barbiturates are usually absorbed very rapidly
DistributionDistribution The more lipid solubility the more entrance the CNS The more lipid solubility the more entrance the CNS (Benzodiazepines: Diazepam & Teriazolam) (Barbiturates: (Benzodiazepines: Diazepam & Teriazolam) (Barbiturates: Thiopental)Thiopental)
RedistributionRedistribution (Barbiturates: Thiopental)(Barbiturates: Thiopental)
Protein binding Protein binding (Benzodiazepines: 60-95%) (Benzodiazepines: 60-95%)
PharmacokineticsPharmacokinetics
Biotransformation Biotransformation --Benzodiazepines:Benzodiazepines: Next slide Next slide
--Barbiturates:Barbiturates: Oxidation & Glucuronide conjugation Oxidation & Glucuronide conjugation ExcretionExcretion - - Both of them are excreted via the kidney,Both of them are excreted via the kidney,
- - 20-30%20-30% of Phenobarbital and of Phenobarbital and tracetrace amount of benzodiazepines amount of benzodiazepines is excreted unchanged,is excreted unchanged, - - Elimination of barbiturates can be increased by alkalinization of Elimination of barbiturates can be increased by alkalinization of urine urine
Pharmacokinetic of BZDPharmacokinetic of BZD
Pharmacokinetic of BZDPharmacokinetic of BZD
Barbiturates:Barbiturates: Potent inducer (cytochrome Potent inducer (cytochrome
p450), cause drug interactions & acute p450), cause drug interactions & acute
porphyriaporphyria
PharmacokineticsPharmacokinetics
Pharmacological effects and usesPharmacological effects and uses
SedationSedation
Hypnosis Hypnosis (decrease in REM duration)(decrease in REM duration) Anesthesia Anesthesia ((BenzodiazepinesBenzodiazepines: midazolam, : midazolam, BarbituratesBarbiturates: thiopental): thiopental) Anticonvulsant action Anticonvulsant action ((Benzodiazepines:Benzodiazepines: clonazepam, diazepam, clonazepam, diazepam, Barbiturates:Barbiturates:
phenobarbital)phenobarbital)
Muscle relaxation Muscle relaxation (Diazepam)(Diazepam)
Tolerance & dependenceTolerance & dependence
CNS depressionCNS depression
Hepatic metabolic uses Hepatic metabolic uses (Phenobarbital in (Phenobarbital in hyperbilirubinemia & kernicterus in neonates)hyperbilirubinemia & kernicterus in neonates)
Pharmacological effects and usesPharmacological effects and uses
Tolerance to sleep facilitationTolerance to sleep facilitation Barbiturates 2 weeksBarbiturates 2 weeks Benzodiazepines 4-6 weeksBenzodiazepines 4-6 weeks
Discontinuation Discontinuation rebound REM Sleep, Psychological rebound REM Sleep, Psychological DependenceDependence
BenzodiazepinesBenzodiazepines
Replaced BarbituratesReplaced Barbiturates
Benzodiazepine AdvantagesBenzodiazepine Advantages --Safer- higher therapeutic indexSafer- higher therapeutic index -Tolerance- lower-Tolerance- lower -Addictive liability- lower-Addictive liability- lower -Less drug interactions-Less drug interactions
Adverse EffectsAdverse Effects
Unwanted daytime sedationUnwanted daytime sedation (especially with (especially with Diazepam, flurazepam)Diazepam, flurazepam) Daytime anxiety and amnesiaDaytime anxiety and amnesia
(especially with(especially with triazolam) triazolam)
Respiratory and cardiovascular depressionRespiratory and cardiovascular depression
(especially with(especially with Barbiturates overdosage) Barbiturates overdosage)
Miscellaneous agentsMiscellaneous agents
5-HT5-HT1A1A partial agonists partial agonists
(Buspirone, Ipsapirone, gepirone)(Buspirone, Ipsapirone, gepirone) AlcoholsAlcohols
(Chloral hydrate, glutetimide)(Chloral hydrate, glutetimide) Other BZ receptor agonistsOther BZ receptor agonists
(Zaleplon, Zolpidem)(Zaleplon, Zolpidem) OthersOthers
Atypical AnxiolyticAtypical Anxiolytic
No hypnotic,anticonvulsant or muscle relaxant No hypnotic,anticonvulsant or muscle relaxant
Acts at 5-HTActs at 5-HT1A1A ((partial agonistpartial agonist)) and Dopamine and Dopamine
receptorsreceptors
Does not produce tolerance and physical dependenceDoes not produce tolerance and physical dependence
Side effect:Side effect: nausea, dizziness, headache, tachicardianausea, dizziness, headache, tachicardia,… ,…
5-HT5-HT1A1A partial agonists partial agonists
Chloral Hydrate: Chloral Hydrate: Metabolized to trichloroethanolMetabolized to trichloroethanol
Short durationShort duration
No enzyme inductionNo enzyme induction
Tolerance/Dependence Withdrawal can Tolerance/Dependence Withdrawal can be severebe severe
AlcoholsAlcohols
BZ receptor agonistsBZ receptor agonists (Zolpidem…)Zolpidem…)
Not a benzodiazepine but binds to BZ receptorNot a benzodiazepine but binds to BZ receptor
Minimal muscle relaxing & anticonvulsant effectMinimal muscle relaxing & anticonvulsant effect
Good hypnotic, with less effects on stages of sleepGood hypnotic, with less effects on stages of sleep
Can suppress REM in higher dosesCan suppress REM in higher doses
Low incidence of rebound insomnia, daytime Low incidence of rebound insomnia, daytime sedationsedation
Side effects:Side effects:
--Respiratory depressionRespiratory depression
-Tolerance less than Benzodiazepines-Tolerance less than Benzodiazepines
BZ receptor agonistsBZ receptor agonists
OthersOthers
MeprobamateMeprobamate RARELY RARELY if ever used, Similar to Barbs.if ever used, Similar to Barbs.
Beta- BlockersBeta- Blockers useful in alleviating performance anxiety.useful in alleviating performance anxiety.
FlumazenilFlumazenil
Benzodiazepine competitive Antagonist, Benzodiazepine competitive Antagonist, no activity in its own rightno activity in its own right
It reverse CNS depressant effect of It reverse CNS depressant effect of Benzodiazepines, Zolpidem and ZaleploneBenzodiazepines, Zolpidem and Zaleplone
Ineffective for most other sedativesIneffective for most other sedatives
Side effects of FlumazenilSide effects of Flumazenil
AgitationAgitation ConfusionConfusion DizzinessDizziness NauseaNausea Seizure & cardiac arrhytmia (patient treated with Seizure & cardiac arrhytmia (patient treated with
TCA)TCA) Transient improvement in mental status has been Transient improvement in mental status has been
reported in patient with hepatic encephalopathyreported in patient with hepatic encephalopathy