藥理學(xué)等多個(gè)老師c16sedative-hypnotics

1、 Chapter 16 Sedative-Hypnotics sedationhypnosis anticonvulsant anti-epilepticanesthesia death1 Benzodiazepines (BZD) Classification1. Short -acting t1/224hrs diazepam, etc Pharmacokineticssome metabolites half-lives greater than the parent drugsPharmacological effects and Clinical Uses1. antianxiety

2、 smaller dose 2. Sedation hypnosis Advantages -REM shortened, but smaller than slow-wave sleep shortened-Therapeutic index is high large dosage dose not induce anesthesia-no hepatic enzyme induction effect-dependent and withdrawal is small 3.Anticonvulsant effects and antiepileptic effects anticonvu

3、lsant Diazepam is used to antiepileptic-status epileptics 4.Central Muscle relaxation reduces muscle rigidity induced by CNS damage5. OthersMechanism of action BZ agonists increase the amount of chloride current generated by GABAA receptor activated potentiate the effects of GABA（open rate）Adverse E

4、ffects ataxia (共濟(jì)失調(diào)) depressive Cardiovasculer and respiratory system drowsiness and lethargy(昏睡) Dependence, tolerance, addiction rebound most commonly -tachycardia，tremor, seizures(5) Others rash, nausea, leukopenia,Benzodiazepine Receptor Antagonist Flumazenil(氟馬西尼) competitive benzodiazepine rec

5、eptor antagonist Uses-BZ intoxication-hepatogenic encephalopathy2 Other Sedative-Hypnotics. BarbituratesPharmacological Effects Barbiturates depress the CNS in adose-dependent fashion sedation hypnosis anticonvulsant (anti-epileptic) Phenobarbita anesthesia Thiopental coma deathMechanism of Actionin

6、crease Cl- influx ,induce hyperpolarization (開放時(shí)間）inhibit glutamate receptorreduce glutamate excitatory effects Clinical Uses1. sedative and hypnoticreplaced by newer drugs2. anticonvulsant3. antiepileptic- phenobarbital grand mal status epileptics 4.anesthesia and pre-anesthesia medication Thiopent

7、al I.V for inducing anesthesia Side Effects hangover(宿醉)- dizziness drowsiness, fatigue hypersensitivity- skin rash。3. tolerance-dependence withdrawal symptoms rebound prolong REM sleep with nightmare2.Chloral Hydrate inducing sleep in 1/2 h, lasting 6 hrs not disturb the balance REM gastrointestina

8、l tract irritating have effect by used shortly ,but no effect by longer than two weeks 3. Zolpidem（佐匹克?。?binds to the BZ1 subtype facilitaes GABA-mediated neuronal inhibition antagonized by flumazenil hypnotic, muscle relaxing, anticonvulsant effects treat insomnia suppress REM sleep higher doses respiratory depression - large dose tolerance and dependence- less than benzodiazepines 4.Zolpidem (唑吡坦） select BZ1 no act on BZ2-n