1、1,Depression and anxiety,Lou haiyan（娄海燕）Institute of PharmacologySchool of MedicineShandong U,2,Depression,Common psychiatric disease, 11% WHO，Depression will become the main killer to people in 21th century,BLUE FLU,3,Depression is an illness that is characterized by a series of changes that gradua
2、lly cause significant impairment of the activity of people concerned.It is more than feeling blue, down in the dumps or sad about a particular issue or situation.It is a medical condition that requires diagnosis and treatment,4,Symptoms of Depression,FIVE OR MORE OF THE FOLLOWING FOR AT LEAST TWO WE
3、EKS:Feelings of sadness, depressed mood and/or irritabilityLoss of interest or pleasure in activitiesChanges in weight or appetiteChanges in sleep pattern-not enough or too much,5,Symptoms of Depression,Feelings of guilt, hopelessness or worthlessnessInability to concentrate, remember things or make
4、 decisionsConstant fatigue or loss of energyRestlessness or decreased activityRecurrent thoughts of suicide or death,6,人很烦？爱发脾气或对你的亲友漠不关心？,7,Hamilton rating scale for depression（汉密尔顿抑郁量表),8,Epidemiology,The most common psychiatric disorderDepression incidence Men: 13%Women: 21%Bipolar disorder: 1.3-
5、1.8%Age of onset: 25-35 yearMajor risk factor: stress,9,Etiology,Biological factorsSocial factorsPsychological factors,10,Biological factors,GeneticHigh prevalence in first degree relativesHigh concordance with monozygotic twinsShort allele of serotonin transported gene,2003Medical illness: Parkinso
6、ns, Alzheimers, cancer, diabetes or strokeVascular changes in the brain Chronic or severe painPrevious history of depressionSubstance abuse,11,Social factors,Loneliness, isolation Recent bereavement Lack of a supportive social network,12,Psychological factors,Traumatic experiencesDamage to body imag
7、e Fear of death Frustration with memory loss Role transitions,13,Neurobiology of depression,The monoamine deficiency theoryDecreased levels or activity of nor-epinephrine and/or serotoninAbnormality in HPA axisHippocampus volume ,14,Treatment for Depression,Approximately 80% of people who receive tr
8、eatment for Depression improve.There are three types of treatment:PsychotherapyMedicationElectroconvulsive Therapy (ECT,电休克治疗),15,Tricyclic antidepressants(TCAs) Monoamine oxidase inhibitors(MAOIs) Norepinephrine reuptake inhibitors(NARIs) Selective serotonin reuptake inhibitors( SSRIs) Serotonin an
9、d norepinephrine reuptake inhibitors(SNRIs),Antidepressant drugs,16,丙米嗪（imipramine）,氯米帕明（ clomipramine ）,阿米替林（amitriptyline）,多塞平（doxepin）,三环类：,.Tricyclic antidepressants (TCA),17,1.CNS： produce inhibition on normal person, elevating the mood that is depressed slow onset:2-3w,Imipramine (丙米嗪，米帕明）,Mec
10、hanisms： block the uptake of NA and 5-HT,【Pharmacological effects and mechanism】,18,2. autonomic nervous system block M-R3. cardiovascular systemhypotension: block 1 Rarrhythmias,tachycardia: NA quinidine-like inhibitory action on heart used with caution in patients with cardiovascular disease,【Phar
11、macological effects and mechanism】,19,【Clinical uses】 1. depressions caused by all kinds of reasons 2. enuresis(遗尿症) in children 3. anxiety and phobia (恐怖症),【Adverse reactions】 1. atropine-like action 2. cardiovascular reaction,20,三环类抗抑郁药的作用及机制,抑制突触前膜对5-HT和NA的重摄取,阻断M-R,阻断1-R,阻断H1-R,奎尼丁样心肌抑制作用,抗抑郁,心律
12、失常,口干、视力模糊、便秘、尿潴留,血压,过度镇静,21,doxepin（多塞平，多虑平）,抗焦虑作用强，对伴有焦虑症状的抑郁 症疗效最佳。,22, Monoamine oxidase inhibitors(MAOIs) ：,异烟肼（isoniazid）,异卡波肼（isocarboxazid）,吗氯贝胺（moclobemide）,Adverse reaction: hypertensive crisis, liver injury,23,【Pharmacological effects and mechanism】 Inhibit MAO, and reduce the degradation
13、 of monoamine.【Clincal uses】: atypical depression not first choice【Adverse reactions】 Severe: hypertension crisis,24, NA reuptake inhibitors,Desipramine (地昔帕明)Maprotiline (马普替林)Nortriptyline (去甲替林) TCA Selectively reduce reuptake of NA Weak sedation and anticholinergic activity Onset rapid,25, Selec
14、tive 5-HT reuptake inhibitors (SSRIs),Fluoxetine (Prozac,氟西汀, 百忧解)Paroxetine (Paxil, 帕罗西汀, 赛洛特)Sertraline (Zoloft,舍曲林, 郁乐复)Fluvoxamine (Luvox,氟伏沙明, 兰释)Citalopram (Celexa,西酞普兰, 喜普妙 ),First line,26,氟西汀（fluoxetine,百忧解）,selectively inhibit 5-HT reuptake no affinity to the receptors in CNS and periphery，
15、less adverse reactions better tolerance and security than TCAs take effects after 2-6 weeks used for depression , compulsion(强迫症) polyphagia(贪食症),27, 5-HT and NA reuptake inhibitors (SNRIs),Venlafaxine (文拉法辛,怡诺思） Duloxetine (度洛西汀）Have advantages over SSRIsFaster onset of action (2mmol/L monitor bloo
16、d drug concentration, withdrawal at 1.6mmol/L,【Adverse reactions】,37,nausea, vomit, abdominal pain, profuse diarrhea, and ataxia, mental confusion, hyper-reflexia, tremor, convulsionIntoxication can be usually reversed by osmotic diuresis or by dialysis (透析),38,Section 3 Anti-anxiety Drugs,39,Anxiet
17、y,Anxiety is an unpleasant emotional experience characterized by fear disproportionate to the severity of stressful factors in the environment, or fear without cause.,40,Anti-anxiety drugs,BenzodiaepinesFirst-line drugsMechanism: binds to GABAA receptor and act as positive allosteric modulators.Busp
18、irone(丁螺环酮）Psychotherapy,41,Buspirone (BuSpar),Partial agonist at the serotonin 1a receptor.Relieves anxiety without producing sedation, impairment of motor skills, or memory loss.Does not induce withdrawal symptoms upon discontinuation.Does not act immediately.Can take up to 1 week to become effective.Used for chronic anxiety states.Pharmacokinetics:Rapidly absorbed orally.Rapid first-pass effect.Elimination half-life = 2-4 hrs.Metabolism is primarily hepatic.,42,Thank you!,
