异戊巴比妥PPT学习教案

1、会计学1异戊巴比妥异戊巴比妥 To inhibit selectively CNS，small dose produces quiet or somnolence, which is called sedation; larger dose produces hypnosis. 第1页/共31页第2页/共31页第3页/共31页【Molecular structure】 Derivates of 1, 4-benzodiazepine. More than 20 commonly-used drugs, e.g. diazepam, oxazepam, flurazepam and triazo

2、lam etc. Their basic actions are similar. Diazepam is their representative and has widespread application.NNR1R2R3R4R2R7第4页/共31页第5页/共31页 Low dose causes antianxiety and eliminates patients restlessness, excitation, horror and anxiety, and anxiety-induced gastrointestinal dysfunction and insomnia. Be

3、ing used to treat various kinds of factors-induced anxiety disorders. Mechanism: impacting BZ receptor in limbic system.Ones much concern and worryinsomnia第6页/共31页 Normal sleep: two phases（alternative）- SWS （non-rapid eye movement sleep，NREMS） and paradoxical sleep（rapid eye movement sleep，REMS） Slo

4、w wave sleep: main part of sleep. Four stages1, 2, 3 and 4.nStage 1 : appearing on the onset of sleep or after short analepsia at nightnStage 2 : the major component of SWS; representing somnolence coursenstage 3 and 4 : deep sleep; promoting physical capacity and energy to recover.SWSREM SWSREM SWS

5、REM SWSRapid eye movements REM123 4 Stage 0Latent periodSlow wave sleep, SWS With the increase of dose-sedation and hypnosis. Shortening sleep latency, reducing awareness number at night and prolonging sleep time (especially stage 2 of NREMS ). Reducing stage 3 and 4 of NREMS (decreasing night terro

6、rs and sleepwalking in them). Being similar to physiological sleep. Paradoxical sleep: periodical excitation state in sleep. Its EEG is similar to that in awareness. The activity of autonomic nervous system increases, e.g. blood pressure and heart rate. Intermittent paroxysmal activities, e.g. frequ

7、ent rapid ocular movement and muscle spasm on limbs extremity and face etc.第7页/共31页第8页/共31页l Adjunctive therapy of tetanus(破破伤风伤风), eclampsia(子痫子痫), drug poison and children ardent fever-induced convulsion.l Diazepam is the drug of first choice of epileptic state.第9页/共31页 Alleviating cerebrum damage

8、-induced muscle rigor and doesnt impact normal movement. Treating cerebral accident, and brain and spinal injury-induced muscle rigor , alleviating arthropathy and lumbar muscle strain-induced muscle spasm and strengthening the muscle relaxation of general anesthetics. 第10页/共31页5.Other Larger dose -

9、temporary memory deficit. Being used in heart shock recovering rhythm and before endoscopy(内窥镜检查内窥镜检查).第11页/共31页 Involving in increasing the function of GABA and impacting the GABAA receptor in the different regions. GABAA is a macromolecular complex, which is a ligand-gated chloride ion channel. 第1

10、2页/共31页第13页/共31页extracellularintracellularChloride ion channelChloride ion channel第14页/共31页BZ+GABAA-R BZ+GABAA-R compound Promoting the binding of GABA and GABAA-R Cl channel open frequency Cl influx Membrane hyperpolarizationThe binding of BZ and GABAA receptor induces the conformational change of

11、the later to promote the binding of GABA and GABAA receptor so that the permeability of membrane on Cl- increases, that causes membrain hyperpolarization and center inhibition.第15页/共31页 Pharmacokinetics l P.O.-quick and complete absorptionl I.m.-chronic and irregular absorptionl Intensive liposolubi

12、lity; easily penetrating blood brain barrier and placental barrierl Plasma protein binding rate- 95%l Hepatic metabolisml Renal excretion第16页/共31页第17页/共31页Adverse Reactionl Somnolence, dizziness, debility and decreasing memory. Large doseataxy(共济失调共济失调) and interfering skill action and drive safety.

13、l I.v.local pain or thrombophlebitis, even the inhibition of respiration and circulationrespiratory and cardiac arrest.l Long usetolerance and dependence; no administration withdrawal symptom.Movement dystaxia, but muscle force is normal; cannot maintain the posture and balance of body.第18页/共31页l Ca

14、utious use: senile patients; hepatic, rental and respiratory insufficiency, driver, machine operator, glaucoma and myasthenia gravis.l Penetrating placenta and appearing in milk-contraindications: antepartum and suckling womenl Overdose toxication: gastric lavage, symptomatic treatment and specific

15、antagonist -flumazenil。第19页/共31页Section 2 Barbiturates Traditional sedative-hypnotics, non-specific central supressants. With the application of BZs (advantages: immediate and high effect, and safety), they are replaced in sedation and hypnosis.第20页/共31页第21页/共31页 Low dosequiet, alleviating anxiety a

16、nd dysphoria. Intermediate doseshortening sleep latency, reducing awareness number and prolonging sleep time, but shortening REMS; long usetolerance and dependence, obvious withdrawal symptoms accompanied by many dreams resulting in sleep disorder第22页/共31页Disadvantages of barbiturates taken as hypno

17、tics:l Easily causing tolerance, dependence and severe withdrawal symptomsl Many adverse reactions; overdosesevere toxicityl Inducing the activities of hepatic enzymes to impact hepatic metabolism of other drugs Therefore, they have not taken as common sedative-hypnotics.第23页/共31页 Phenobarbital: int

18、ensive anti-convulsion and epilepsy. Treating many cause-induced convulsionseliminating the convulsion of tetanus, eclampsia and children ardent fever etc. Phenobarbital and pentobarbital may be used to treat grand mal and status epilepticus. 第24页/共31页 Long and intermediate actingpreanesthetic medication, but their effects are inferior to diazepam. Some short and ultra-short acing (e.g. pentothal) can cause short anesthetic action and be used in the inductive and intravenous anesthesia.第25页/共31页BarbitalCl-BZ receptorGABA receptorCl- channelCl-GABA+-+-GABAA receptor：ligand-gated Cl- channel第