临床药理学问题答案鸣谢：沈剑波、王海林、孙俊龙、张玉鑫、汤晨雪、吴慧、郑雅、戴璐、方淼、孔亚男、张舒文、徐阳、蔡水灵、刘珊等同学的无私奉献整理：临床小胖子一、please illusrate how to develop a new drug(p4)Most new drugs or drug products are discovered or developed through the following approaches:(1)identification or elucidation of a new drug target;(2)Rational design of a new molecule based on an understanding of biologic mechanisms and drug receptor structure;(3)Screening for biologic activity of large numbers of natural products,banks of previously discovered chemical entities,or large libraries of peptides,nucleic acids,and other organic molecules;(4)Chemical modification of a known active molecule,resulting in a me-too analog.Steps(1) and (2) are often carried out in academic research laboratories ,but the costs of steps(3) and (4) usually ensure that industry carries them out.二、Please tell the meaning of loading dose and maintenance dose?(p17)Loading dose is one or a sevies of doses that may be given at the onset of therapy with the aim of achieving the target arcentration vapidly .a loading dose may be desirable if the time required to attain steady state by the administration of drug at a anstant rate is long relative to the temporal demands of the condition being treaded.Maintenance dose : Maintenance dose is the dose that continues to keep the drug in the dosing therapeatic range. In most clinical situations, drugs are administered in a sevies of repetitive doses or as a wntinuous infusion to maintain a steady state concentration of drug associated with the therapeatic window. Calculation of the appropriate maintain dosage is a primary goal. To maintain the chosen steady state or target concentration, the rate of drug administration is adjusted such that the rate of input equals the rate of loss.三、Please tell the classification of ADR?(p24)ADR can be divided into three groups according to onset ①acute:within 60 minutes②sub-acute:1 to 24 hours③latent:≥2 days. It can also be divided into another three groups because of severity ①mild:bothersome but requires no change in therapy ②moderate:require change in therapy,addition treatment, hospitalization ③severe:disabling or life-threatening四，How to access ADR(p33)ADR can be evaluated by causality assessment .You can access the ADR from the following aspects:1.If the reaction had prior reports?2.temporal relationship3.de-challenge4.re-challenge5.Close-response relationship6.Alternative etiologies7.Objective confirmation8.If the patient had past history of reaction to same or similar medication .According to the results,the ADR can have four outcomes:highly probable,probable,possible and doubtful.五，what’s the sympoms of schizophrenia.(p39)Postitive symptoms:1.Delusions2.Hallucinations3.Thought disorder4.Abnormal.disorganized behaviour5.CatatoniaNegative symptoms:1.withdrawal from social contacts2.Flatten of emotional response3.Anhedonia(en inability to experience pleasure)4.Reluctance to perform everyday tasks.In addition,deficits in cognitive function are often present together with anxiety,guilt,depression and self punishment.A characteristic feature of schizophrenia is a defect in “selective attention”.Whereas a normal individual quickly accommodates to stimuli of a familiar or inconsequential nature,and responds only to stimuli that are unexpected or significant,the ability of schizophrenic patients to discriminate between significant and insignificant stimuli seems to be impaired六．what kinds of antidepressant drugs are used in clinic?(p53)Antidepressant drugs fall into the following categories：1.Inhibitors of monoamine uptakeSelective serotonin (5-HT) reuptake inhibitors (SSRJs): fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopramClassical tricyclic antidepressants (TCAs): imipramine, desipramine, amitriptyline, nortriptyline, clomipramine; varying in their ability to inhibit noradrenaline and 5-HT reuptakeNoradrenaline reuptake inhibitors: bupropion, reboxetine, atomoxetineNewer, mixed 5-HT and noradrenaline reuptake inhabitors: bupropion, desvenlafaxine, duloxetine, milnacipran 2.Monoamine receptor antagonistsDrugs such as mirtazapine, trazodone, mianserin are non-selective and inhibit a range of amine receptors including a2 adrenoceptors and 5-HT2 receptors. They may also have weak effects on monoamine uptake3.Monoamine oxidase inhibitors(MAOIs)Irreversible, non-competitive inhibitors: phenelzine, tranylcypromine,which are non-selective with respect to the MAO-A and -B subtypesReversible, MAO-A-selective inhibitors: moclobemide个人觉得只需答第1点即可。