1、Sedative and hypnoticDrugs2024/11/291Dr.Lei Chen from the department of PharmacologyDefinitions A sedative drug decreases activity,modulates excitement,and calms the patient.A hypnotic drug produces drowsiness and facilitates the onset and maintenance of a state of sleep that resembles natural sleep
2、,and from which the patient can be easily aroused.2024/11/292Dr.Lei Chen from the department of Pharmacology SLEEP stages NREMS REMS NREMS REMS：NS development，memory,dream NREMS：1,2 stages 3,4 stages(Slow wave sleep，SWS)growth,restore2024/11/293Dr.Lei Chen from the department of Pharmacologyn REMS N
3、REMS SWSnBarbiturates nBenzodiazepines nChloral hydrate 2024/11/294Dr.Lei Chen from the department of PharmacologyTreatment for insomnianRemove original diseasesnDrug therapy is only adjunctive method for non-drug treatmentnThe least dosage and shortest periodnDisadvantages:nTolerance(enzyme inducti
4、on,desensitivity)nPhysical/psychic dependence2024/11/295Dr.Lei Chen from the department of PharmacologyClassification nBenzodiazepinesnDiazepamnChlordiazepoxidenClonazepamnTriazolam nBarbituratesnAmobarbitalnphenobarbital nThiopentalnOther drugsnChloral hydrateSmall dose:Small dose:sedationsedationL
5、arge dose:Large dose:hypnosishypnosis;anticonvulsantanticonvulsant;anesthesia;anesthesia2024/11/296Dr.Lei Chen from the department of PharmacologyBenzodiazepines BDZsDiazepamDiazepamOxazepamOxazepamTriazolamTriazolam2024/11/297Dr.Lei Chen from the department of PharmacologyD DrugsrugsElimination hal
6、f Elimination half life(hours)life(hours)DosageDosage（mgmg）sedativesedative hypnotic hypnoticD Diazepamiazepam30603060 2.552.55 tidtid510510OOxazepamxazepam5105101530,1530,qd,tidqd,tid15301530Triazolam1.531.53-0.250.50.250.5（15301530min)min)Benzodiazepines BDZs2024/11/298Dr.Lei Chen from the departm
7、ent of PharmacologyMechanism:Promote GABA receptor functionMechanism:Promote GABA receptor functionn ligand-gated chloride channeln-butylamino acid,GABA n Basic structure:GABA A receptor consists of two1,two 2 and one 2 subunits.n GABA A receptor,which functions as a chloride ion channel,is activate
8、d by the inhibitory neurotransmitter GABA.2024/11/299Dr.Lei Chen from the department of PharmacologynGABA binds to GABAA receptor Cl-membrane hyperpolarization inhibitionnThe binding site for BDZs(BDZ-receptor)is located between andsubunit.2024/11/2910Dr.Lei Chen from the department of Pharmacologyn
9、BDZs nimprove GABA binding to GABAA receptor.nincrease frequency of channel-opening events of chloride ion channel.nGABA increases the binding between BDZs and receptornBicuculine(GABA receptor blocker)can block the effectsnAntianxity effect:amygdala,hippocampus receptornHypnotic effect:brain stem n
10、ucleus receptor2024/11/2911Dr.Lei Chen from the department of Pharmacology antianxity action The anxiolytic actions can be occurred at lower dosage.It selectively inhibit neuronal circuits in the limbic system of the brain.Sedative and hypnotic actions useful in sleeping disorders,which mainly prolo
11、ng stage 2 of NREMS,shorten SWS and latency of sleep onset.the most popular sedative and hypnotic drugDiazepam（valium）-Action and uses2024/11/2912Dr.Lei Chen from the department of PharmacologynAdvantagesnHigher Therapeutic index,safenLess effect on REM,so less rebound than barbiturate;shorten or ca
12、ncel phase 4 of NREM,decrease occurrence of night terrors or night walkingnNo effect on liver drug enzyme and metabolisms of other drugsnLess dependence and abstinence syndromenLess side effects:drowsiness,ataxia(incoordination)2024/11/2913Dr.Lei Chen from the department of Pharmacology Anticonvulsa
13、nt and antiepileptic actionLimit transmit from site of epilepsy to near tissue,although it can not cancel the dischargeTetanus,eclampsia,febrile convulsion i.v.diazepam is the best choice for status epilepticus Central muscle relaxantWithout impairing involuntary activityTreatment for central myoton
14、ia caused by cerebral accident or spinal cord injury and other muscle spasmDiazepam（valium）-Action and use2024/11/2914Dr.Lei Chen from the department of PharmacologynOther nLose memorynRespiratory depression:large dosenCVS:Bp and heart rate decreasenPreanesthesia medication:in order to decrease the
15、dose of anesthesia drugs2024/11/2915Dr.Lei Chen from the department of Pharmacologyncommon:hypersomnia,drowsiness,ataxia,impaired judgment,diminished motor skills.n i.v.too fast -respiratory and cardivascular inhibition and CNS depression,even heart arrestn rarely fatal even following very high dose
16、sn contraindications:the presence of other central nervous system depressants;child,elder patients；patients with severe liver diseaseSide effects:2024/11/2916Dr.Lei Chen from the department of PharmacologynTolerance:fast for hypnotics and slow for antianxietic nDependencenPsychological and physical
17、dependence on BDZ can develop if high doses are given during long periodsnDiscontinuation can cause confusion,anxiety,agitation,restlessness,etc.nTriazolam induces more abrupt and severe withdrawal reactions than those with long eliminations.n Fetal deformation 2024/11/2917Dr.Lei Chen from the depar
18、tment of PharmacologyTreatment of intoxication:Ensuring the living symptomMaintenance of plasma volume,renal output,cardiac functionpurging the stomach；HemodialysisBDZ receptor antagonist-flumazenil2024/11/2918Dr.Lei Chen from the department of PharmacologyBarbituratesDrugt(h)Onset(h)duration(h)Long
19、 actionPhenobarbital(luminal)24-1400.5-16-8Middle actionAmobarbital(amytal)8-420.25-0.53-6Short actionSecobarbital19-340.252-3Super short actionThiopental3-830s i.v.1-4Classification2024/11/2919Dr.Lei Chen from the department of PharmacologyMechanismnIt imitates GABA and activates GABAA receptor,pot
20、entiates GABA action and chloride entry into the neuron.n Barbiturates:prolong opening duration of Cl-channel n BDZ:increase the opening frequency of Cl-channel 2024/11/2920Dr.Lei Chen from the department of PharmacologyActions(sedative,hypnotic,anticonvulsion,antiepilepsy,anesthesia)nDepression of
21、CNSnLow doses-sedationnHigh doses-hypnosis followed by anesthesia,coma and deathnno analgesic propertynRespiratory depressionninhibit chemoreceptor response to CO2 and hypoxicnEnzyme induction ninduce P-450 microsomal enzyme in the liver2024/11/2921Dr.Lei Chen from the department of PharmacologyUse:
22、sedative and hypnosisl shorten REMS,reboundl dose dependence anticonvulsant(phenobarbital):febrile convulsion,tetanus,eclampsia,status epilepticus,grand mal anesthesia and preanesthetic medication(thiopental)super-short-acting barbiturates,i.v.to induce anesthesia to calm,remove tensionPotentiate th
23、e actions of CNS inhibitors:combine with other antipyretic analgesics 2024/11/2922Dr.Lei Chen from the department of PharmacologyAdverse effectAdverse effect drug hangover:tiredness after awakes,drowsiness,ataxia,difficult to concentrate,and mental and physical sluggishness.tolerance:induce P-450 sy
24、stem addiction:withdrawal syndrome may cause tremor,anxiety,weakness,restlessness,nausea and vomiting,seizure,delirium,cardiac arrest.respiratory depressionPass placenta barrier and secret into milk allergy:urticaria2024/11/2923Dr.Lei Chen from the department of PharmacologyIntoxication and rescuein
25、toxication:overdoses can cause death,depression of respiration and central cardiovascular depression.Treatment:partificial respiration;ppurging the stomach of its contents;alkalinization of blood and urine(sodium bicarbonate);phemodialysis2024/11/2924Dr.Lei Chen from the department of Pharmacology I
26、nduces sleep in about 15 minutes and lasts 68 hours.Irritates to the gastrointestinal tract and causes epigastric distress,also produces an unusual,unpleasant tasteUsually via rectumOther sedatives-Chloral hydrate2024/11/2925Dr.Lei Chen from the department of Pharmacology2024/11/2926Dr.Lei Chen from
27、 the department of PharmacologyReview questionsnWhat are the mechanisms of BDZ and barbiturates,and the differences between them?nHow to rescue poisoning of BDZ and Barbiturates?nWhat are the actions and clinical uses of BDZ and barbiturates?2024/11/2927Dr.Lei Chen from the department of PharmacologyPreview questionsnWhat are the mechanisms and uses of antiepileptics?nHow to use antiepiletics to treat different type epilepsy?nWhat is the actions of MgSO4 via different administration route?2024/11/2928Dr.Lei Chen from the department of Pharmacology
