1. Anxiolytic and HypnoticAnxiolytic and Hypnotic
DrugsDrugs

2. NeurotransmittersNeurotransmitters
• Excitatory NTsExcitatory NTs
– Key words: sodium, calcium, depolarizationKey words: sodium, calcium, depolarization
• Inhibitory NTsInhibitory NTs
– Key: chloride, GABA, hyperpolarizationKey: chloride, GABA, hyperpolarization

3. AnxietyAnxiety
• Fear, apprehension and worryFear, apprehension and worry
• Accompanied by physical sensations suchAccompanied by physical sensations such
as anxiety, nausea, chest pain and/oras anxiety, nausea, chest pain and/or
shortness of breathshortness of breath

4. AnxietyAnxiety
• Generalized anxiety disorderGeneralized anxiety disorder
• Panic attacksPanic attacks
• PhobiaPhobia
• Obsessive-compulsive disorderObsessive-compulsive disorder
• Post-traumatic stress disorderPost-traumatic stress disorder

5. Sedatives-HypnoticsSedatives-Hypnotics
• BenzodiazepinesBenzodiazepines
– Increase theIncrease the frequencyfrequency of GABA-mediatedof GABA-mediated
chloride ion channel openingchloride ion channel opening
• BarbituratesBarbiturates
– Increase theIncrease the durationduration of GABA-mediatedof GABA-mediated
chloride ion channel openingchloride ion channel opening

6. Classes of Anxiolytic andClasses of Anxiolytic and
Hypnotic drugHypnotic drug
• BenzodiazepinesBenzodiazepines
– 5-HT1A-receptor agonists5-HT1A-receptor agonists
– β-adrenoceptor antagonistsβ-adrenoceptor antagonists
• BarbituratesBarbiturates

7. BenzodiazepinesBenzodiazepines
• Act by binding to a specific regulatoryAct by binding to a specific regulatory
site on the GABA A-receptorsite on the GABA A-receptor
• enhances the inhibitory effect of GABA.enhances the inhibitory effect of GABA.
• Subtypes of the GABA A-receptor existSubtypes of the GABA A-receptor exist
in different regions of the brainin different regions of the brain
– differ in their sensitivity todiffer in their sensitivity to
benzodiazepines.benzodiazepines.
• Anxiolytic benzodiazepines are agonistsAnxiolytic benzodiazepines are agonists
at this regulatory site.at this regulatory site.

10. ACTIONSACTIONS
• Reduction of anxietyReduction of anxiety
• Sedative – hypnoticsSedative – hypnotics
• AnticonvulsantAnticonvulsant
• Muscle relaxantMuscle relaxant

11. Clinical Pharmacology ofClinical Pharmacology of
BenzodiazepinesBenzodiazepines
• Long half-livesLong half-lives
• DiazepamDiazepam
– commonly used for anxiety, alcohol withdrawal,commonly used for anxiety, alcohol withdrawal,
seizuresseizures
• ChlordiazepoxideChlordiazepoxide
– alcohol withdrawalalcohol withdrawal

12. Clinical Pharmacology ofClinical Pharmacology of
BenzodiazepinesBenzodiazepines
Mid-half livesMid-half lives
• OxazepamOxazepam
– not metabolized in the livernot metabolized in the liver
• TemazepamTemazepam
– used as hypnoticsused as hypnotics
• AlprazolamAlprazolam
– anxiolytic and hypnoticanxiolytic and hypnotic
• LorazepamLorazepam
– not metabolized in the livernot metabolized in the liver
– anxiolytic longer duration after single dose thananxiolytic longer duration after single dose than
diazepamdiazepam
– less used for alcohol withdrawal because of shorter halfless used for alcohol withdrawal because of shorter half
life (repeated administration)life (repeated administration)

13. Clinical Pharmacology ofClinical Pharmacology of
BenzodiazepinesBenzodiazepines
Short half livesShort half lives
• MidazolamMidazolam
– very rapid onsetvery rapid onset
– Used for conscious sedationUsed for conscious sedation
– short acting sedative (MRI etc)short acting sedative (MRI etc)
• TriazolamTriazolam
– used as hypnoticused as hypnotic
– minimal hangover the following morningminimal hangover the following morning
• FlumazenilFlumazenil
– competitive antagonist of benzodiazepinecompetitive antagonist of benzodiazepine
– leads to benzodiazepine withdrawalleads to benzodiazepine withdrawal seizureseizure

14. 5-HT1A Agonists as Anxiolytic5-HT1A Agonists as Anxiolytic
DrugsDrugs
• BuspironeBuspirone
– potent (though non-selective) agonist at 5HT1A-potent (though non-selective) agonist at 5HT1A-
receptors.receptors.
– Lacks anti-seizure and muscle relaxant properties asLacks anti-seizure and muscle relaxant properties as
benzodiazepinesbenzodiazepines
– Headache, minimal tolerance and withdrawalHeadache, minimal tolerance and withdrawal
– Anxiolytic effects take days or weeks to develop.Anxiolytic effects take days or weeks to develop.
• Ipsapirone and Gepirone are similar.Ipsapirone and Gepirone are similar.
– Side effects include dizziness, nausea, headache, butSide effects include dizziness, nausea, headache, but
not sedation or loss of coordinationnot sedation or loss of coordination

15. BarbituratesBarbiturates
• BarbituratesBarbiturates
•Non-selective CNS depressantsNon-selective CNS depressants
•Sedation and unconsciousnessSedation and unconsciousness
•Bind to the GABA receptor andBind to the GABA receptor and
enhances activityenhances activity
•potent inducers of hepatic drug-potent inducers of hepatic drug-
metabolising enzymesmetabolising enzymes
•Tolerance and dependenceTolerance and dependence
occur.occur.

16. MODE OF ACTIONMODE OF ACTION
• Interferes with Na and K transportInterferes with Na and K transport
• Potentiates GABA action on ClPotentiates GABA action on Cl

17. THERAPEUTIC USESTHERAPEUTIC USES
• AnesthesiaAnesthesia
• AntoconvulsantAntoconvulsant
• AnxietyAnxiety

18. ACTIONSACTIONS
• Depression of CNSDepression of CNS
• Respiratory depressionRespiratory depression
• Enzyme inductionEnzyme induction

19. BarbituratesBarbiturates
phenobarbitalphenobarbital LongLong
1 -2 days1 -2 days
22ndnd
-line anti--line anti-
seizureseizure
Secobarbital,Secobarbital,
pentobarbitalpentobarbital
ShortShort
3 – 8hrs3 – 8hrs
powerfulpowerful
sedativesedative
Thiopental,Thiopental, Ultra-shortUltra-short
20min20min
AnestheticAnesthetic
agentagent
(rapid onset)(rapid onset)

20. ADVERSE EFFECTADVERSE EFFECT
• CNSCNS
• Drug hangoverDrug hangover
• AddictionAddiction

21. Other NotesOther Notes
• Benzodiazepines have no analgesicBenzodiazepines have no analgesic
propertiesproperties
• Fatality of alcohol and benzodiazepinesFatality of alcohol and benzodiazepines
• Hypnotics does not induce REM so lessHypnotics does not induce REM so less
restful than normal sleeprestful than normal sleep
• Longer acting drugs are easier to dose soLonger acting drugs are easier to dose so
effective in alcohol withdrawaleffective in alcohol withdrawal