药物化学案例
药物化学与药物研发案例
药物化学与药物研发案例药物化学是药物研发中的重要领域，药物设计、合成、性质和治疗作用等都是需要药物化学家进行研究和分析的。
本文将介绍几个药物研发成功的案例，并分析了药物化学在这些案例中的作用。
1. 阿司匹林阿司匹林（Aspirin）是一种非甾体类抗炎药，也是最常用的解热镇痛药之一。
它的历史可以追溯到古代时期，人们发现白柳树皮可以用来缓解疼痛。
药物化学家在分离出白柳树皮中的有效成分后，经过多次合成和改良，最终制得了阿司匹林。
药物化学在阿司匹林的研发过程中起到了关键作用。
药物化学家通过对各种合成路线的研究和比较，最终确定了一种合成方法，这种方法具有高效、成本低、易于控制等优点。
同时，药物化学家还对阿司匹林的物理、化学性质进行了深入研究，增加了阿司匹林的稳定性和药效，使其成为一种安全有效的药物。
2. 头孢菌素头孢菌素（Cephalosporin）是一类广谱抗生素，用于治疗各种感染性疾病。
头孢菌素的研发始于20世纪50年代，经过长期的努力，最终在60年代初取得了成功。
药物化学在头孢菌素的合成过程中发挥了重要作用。
药物化学家从天然的青霉素中提取出杆菌素，经过多次合成、扩大规模生产和改良，最终制得了头孢菌素。
药物化学家还对头孢菌素的结构和化学性质进行了深入研究，不断改进其合成路线和生产工艺，提高了头孢菌素的纯度和效力，使其成为一种重要的抗生素药物。
3. 贝伐单抗贝伐单抗（Bevacizumab）是一种针对血管内皮生长因子的单抗药物，用于治疗多种恶性肿瘤。
它的研发历程中，药物化学起到了重要作用。
贝伐单抗的研发始于20世纪80年代，并历经两个十年的时间。
药物化学家在贝伐单抗的开发过程中，不断改进其制备方法和纯化工艺，提高了药物的质量和效能。
药物化学家还对贝伐单抗的结构进行了深入研究，不断改进其结构，提高了药物的亲和力和生物稳定性，使其成为一种安全有效的肿瘤治疗药物。
结论药物化学在药物研发中起到了重要的作用，它不仅负责药物的设计和合成，还研究药物的结构、性质和疗效等，为制药提供了科学依据。
药物化学研究案例
CASE STUDYMedicinal ChemistryCase 1A dentist calls your pharmacy and asks you prepare an antiseptic mouthwash for a patient with a painful bacterial infection of the oral cavity. You ask your second-year pharmacy intern to research the project, and she suggests combining bupivacaine hydrochloride (local anesthetic) with cetylpyridinium bromide(antiinfective)Case 1-Q1 Identify the acidic, basic, or neutral character of the two drug molecules in the case based on salt name.Case 1-Q2 Are these species ionized or unionized in salt form?Case 1-Q3 From an acid-base standpoint, is the mouthwash suggestion sound?Case 3A distraught mother calls the poison control center where you work. Her 6-year-old son just are half a bottle of NH4Cl tablets meant for the family cat. As a complication of morbid obesity, He is hypertensive (the son not the cat), and has been on timolol maleate (blockadren) for 6 months. A significant fraction of timolol is excreted unchanged in the urine, and an overdose can result in bradycardia and hypotension.Case 3-1Q From an acid-base standpoint, is this a potential medical emergency? Why, or whynot?Case 5ZT, a 26-year-old single mother of four with a history of depression, is rushed unconscious to the emergency room of the hospital where you work. The attendant hands you an empty bottle that had contained 10 tablets of amobarbital sodium (pKa = 8.0) After stabilizing respiration and performing gastric lavage, you decide to enhance the renal elimination of the drug .ZT has a urinary pH of 6.0.H NNOOONa pKa = 8.0Case 5 –Q1 What is the acid-base character of amobarbital sodium?Case 5 –Q2 What would be the ratio of ionized to unionized drug forms in this patient ’s urine?Case 5 –Q3Would you recommend the IV administration of NH4Cl or NaHCO3?Case 5 –Q4The ER nurse is preparing to add phentermine hydrochloride to the IV bag containing the pH modifier you have just elected. Would you stop him? Why, or why not?, HClONHCase 17You are an M.D./Ph.D. (in medicinal chemistry, of course) practicing general medicine in the early 1930s. The medical community is all atwitter about a new anti-infective, sodium sulfanilamide, which has shown value in the treatment of urinary tract infections and infection secondary to burns. You are concerned, however, about the tendency of this agent to cause crystalluria, which can result in severe, life-threatening kidney damage. The pKa of sulfanilamide (17.1) is 10.4.Case 17-Q1 Draw the structure of Sodium Sulfanilamide .Case 17-Q2Why would a patient with a urinary pH of 5.4 be at greater risk for the development of crystalluria than one with a urinary pH of 6.4? What would be the ratio of ionized to unionized sulfanilamide drug forms at each urinary pH?Case 17-Q3 Which urinary pH modifier would you prescribe for a patient who began to show symptoms of crystalluria, NH4Cl or NaHCO3?Case 17-Q4 As a medicinal chemist, you understand the impact of structure on the therapeutic profile of drug molecules, and drug design visions are now dancing in your head. Which of the three modified sulfanilamide structures (17.3~17.5) would have a higher therapeutic index with regard to crystalluria? What is the structural basis for your answer?17.1SNH2H2N O OH17.3SNH2NO ONNH17.4SNH2N O O OH17.5SNH2NO OCase 28LP, a prepharmacy student attending a local junior college, has been taking organic chemistry (her favorite class) and has been starting to really understand organic structures. She has been seeing her physician regularly for allergy problems that are particularly troublesome in the fall (ragweed season ). She has been taking diphenhydramine (28.1) for more than a year now, but it is really bothered by the dry mouth and sleepiness that she has come to associate with takingthis drug. Lately, she has been drinking lots of colas to stay awake in organic chemistry and combat the dry mouth. She now thinks that she is dependent on caffeine. You are the pharmacist on duty at the drug store when LP ’s physician calls to ask for advice regarding an alternative medication.Case 28-Q1 Explain the reasons for the side effects that have been observed with diphenhydramine(28.1).O NCH 3CH 328.1Case 28-Q2 Recommend one of the following drugs as an appropriate choice for this patient. Justify your choice and discuss briefly why the other choices are inappropriate. 28.2 Ranitidine28.3 chlorpheniramine 28.4 cetirizine 28.5 Bethanechol28.2OS NHNH 2NO 2NCH 3CH 3NNCH 3CH 3Cl28.3NNCH 3CH 3Cl28.3ClH NNOOOH . 2HCl28.428.5H 3C N O NH 2H 3CCH 3CH 3OCase 46Imagine yourself as drug information specialist at a poison control center. A technician from the coroner ’s office is investigating a case and requires assistance in identifying the possible sources of benzodiazepines (BZDs) in the toxicology profile of a particular corpse. The technician has identified four distinct BZDs in the blood sample. She believes that the major component is diazepam (46.1) (72% of the identified BZDs) and that the remaining three compounds are metabolites (NOTE: the assay identifies only active compounds).Case 46 –Q1What are the three structures of potential ACTIVE metabolites for diazepam (46.1)?Case 50SA is a 20-year-old university coed who presents to the student health service complaining of extreme nervousness, irritability, and difficulty concentrating. For the past year, SA has constantly worried about achieving sufficiently high grades in her prepharmacy courses to qualify for entry into the Doctor of pharmacy program. She is also concerned about her skin condition, which has worsened since she entered the university 2 years age’s has suffered from atomic dermatitis since high school, a condition which until recently had been kept under control using topical hydrocortisone (0.5% cream). As the time for her interview with the College of Pharmacy admissions committee approaches, SA’s worry increase, and she has become increasingly agitated, is unable to concentrate on her studies, and has shortness of breath and palpitations . To make matters worse, the itching rash on her face and arms has worsened.The student health physician, in consultation with SA’s family doctor, decides on a diagnosis of generalized anxiety disorder (GAD). The two physicians agree that a benzodiazepine is indicated.Case 50-Q1 Select a benzodiazepine from the structures (50.1-50.5) provided that would be the most appropriate for treating SA’s anxiety. Justify your choice on the basis of structure/potency and duration of action/relationships. Eliminate inappropriate choices on the same basis.Case 50-Q2How long should SA maintained on anti-anxiety medication? Explain fully.Case 50-Q3What are you going to do for the patient’s atopic dermatitis?Case 83FP is a 62-year-old male vintner with hypertension that is not well controlled on hydrochlorothiazide 50 mg daily and captopril 50 mg tid. Blood pressures on treatment ranges from 160 to 170 systolic and 95 to 105 diastolic. Ten days ago, FP developed a cold that initially got somewhat better, but the worsened over the last 3 days, with the development of facial pain below the eyes, which is made worse when he bends over; a purulent nasal dis charge that “tastes and smells foul”; and a fever of 101 F. The doctor plans to treat the sinusitis with amoxicillin 500mg tid for 3 weeks and wants decongestant treatment for the first 3 to 5 days, but is concerned about its effect on FP’s blood pressure.FP used Dristan nasal spray for his cold, but stopped because “it made me jittery”. The doctor calls asking for a recommendation for a decongestant that will exert minimal effect on blood pressure and won’t make FP feel jittery.Case 83-Q1 Select a decongestant from the structures (83.1~83.5) provided that you would recommend for FP. Explain your rational on a structure/activity basis.83.1N NClNH OH83.2NH2 OH83.3NNHHO83.483.5NHOHHOCase 84As the inpatient pharmacist at Bigshots University Hospital, you have received a call from a medical student for some drug information. This medical student is working on a case presentation for a patient who has been ordered Aldomet 500 mg IV q6h. His question for you is:why would an IV solution be prepared with α-methyldopate hydrochloride (Aldomet IV [84.1]) rather than α-methyldopate (Aldomet [84.2])?Case 84- Q1 Why would an IV solution be prepared with α-methyldopate hydrochloride (Aldomet IV [84.1]) rather than α-methyldopate (Aldomet [84.2])84.1.HClNH 2HOHO O O 84.2NH 2HOHO OH OCase 86HS, a western Nebraska farmer, is brought by his wife to the emergency room of your local hospital with a broken leg. His also complaining of weakness and dizziness, which he is attributing to the pain of his break. You also note that he is salivating and sweating excessively, has a low heart rate, and is breathing with some difficulty. You discover that, in the farm accident which caused the broken leg, he came in contact with large quantities of the insecticide Parathion(硝苯硫磷酯)(86.1).86.1O 2NOP CH 3O CH 3SCase 86-Q1 Explain the cause of the farmer’s symptoms.Case 86-Q2 Which of structures (86.2~86.5) should be immediately administered? Why?86.2+CH 3H O OH86.3Cl -+N 3NOH86.4Cl -+H 2NON CH 3O CH 386.5Br-+O NCH 3OCH 3N CH 3CH 3Case 88LN is a 74-year-old woman who presents to her HMO with malaise, shortness of breath, and fatigue. She also complains of weight gain and swollen hands and feet. LN has a 6-month history of congestive heart failure (CHF), a 3-year history of hypercholesterolemia, and a 6-year history of adult onset (type II) diabetes mellitus. Two weeks ago, LN suffered a mild stroke and washospitalized for 3 days. She was then discharged with a prescription for oral warfarin (5 mg daily ) for 3 weeks. Her other current medications include: digoxin (0.125mg daily), lovastatin (20mg at night), and tolazamide (250mg daily). The patient’s creatinine clearance is 35 mL/min. The cardiologist determines that the digoxin alone is insufficient to control LN’s congestive heart failure. Because previous attempts to use angiotensin-converting enzyme inhibitors caused intolerable hypotension, it is decided to employ diuretic therapy.Case 88-Q1 Which diuretic(s), of the structures (88.1~88.6) shown, would provide the most benefit? Justify your choice(s).Case 88-Q2 Indicate agents that would be inappropriate and/or less effective than your first choice. Explain why.88.1N OCl H 2NO 2SOHH H N S Cl H 2NO 2SO OCl88.2N N N N H 2NNH 2NH 288.3Cl OClOOH 88.4H NNCl H 2NO 2SO 88.5H OHN OH 2NO 2S88.6Case 90AG , is a 56-year-old construction worker with a 15-year history of hypertension and ischemic heart disease that was well controlled until 6 months ago, when he began having anginal chest pain with increasing frequency and severity. Over the past 2 months, has been seen twice in the ER with chest pain unrelieved by sublingual nitroglycerin. On a third occasion, he was hospitalized with the same symptoms and was given a complete workup. He has severe two vessel disease ,but refuses angioplasty or bypass surgery at this time. His current medications include nifedipine XL, captopril, nitroglycerin ,diltiazem, and aspirin .During the past week, he experienced several anginal attacks each day that were relieved by nitroglycerin; finally, AG has decided to seek more definitive treatment. Tonight he presents to the ER with chest pain unrelieved by nitroglycerin and is sent to the critical care until with the diagnosis of unstable angina pectoris. The attending physician orders IV nitroglycerin and wants to start an IV β-adrenergic blocker to counteract any tachycardia ,but is concerned about its long-term effects on overall cardiac function.Case 90-Q1 Select the most appropriate β-adrenergic antagonist from the structures (90.1~90.6) provided. Justify your choice on the basis of the pharmacology and the comparative pharmacokinetics of the available structures.Case 90-Q2 one of the structures is contraindicated in the patient. Which one is it, and why is it contraindicated?90.1HHN OOHN90.2NOHHOHONOH90.3HONOH O90.4HONOH OO90.5H90.6ONOH HCase 100RV , a student from the local community college,is standing in the OTC section of your pharmacy looking miserable and reading the backs of three product packages. He is trying to select something that will help him get over the cold of the century, and expresses anxiety about being ill with autumn midterm examinations coming up in a few days. Normally quite healthy, he appears very congested and feels “achy ”, but his lungs are still clear. He is taking Nodoz prn (which contains caffeine) to help him stay up nights to study, and admits to no allergies. The products he has pulled off the shelf contain the following chemical compounds.100.1+OH O -O HCH 3N ClCH 3 Cl -+CH 3NH 2OHCH 3100.2 Cl -+NH 3CH 3100.3Case 100 –Q1 What pharmacologic class of the molecule dose RV require? Which of the structures provided (100.1~100.3) fall into this pharmacologic class?Case 100 –Q2 Of the agents (100.1~100.3), which would you recommend? How dose the chemistry of your agent of choice support your recommendation?Case 114Dr.Iris Brown,an ophthalmologist, is seeing a patient with corneal inflammation .She wishes to initiate topical antimuscarinic therapy ,and is considering the merits of the compounds shown (114.1~114.5). Dr. Brown wishes to formulate a potent antimuscarinic in a standard lanolin-based ointment and asks your advice on which product to choose.Case 114-Q1 What chemical property would be most important in a drug molecule destined for a lanolin-based ointment base?Case 114-Q2 What structural features contribute to high antimuscarinic potency in Solanaceous alkaloid molecules?Case 114-Q3 Which of the five contemplated structures(114.1~114.5) would you recommend to Dr. Brown?Case 114-Q4 If Dr. Brown ’s patient returned to her clinic after a number of days on your drug of the choice complaining of dry mouth and blurred vision, how might this be explained?Case 114-Q5 Which of the original five molecules (114.1~114.5) would you have selected if Dr. Brown had wanted to prepare an ophthalmic solution for her patient? Could you have easily modified the structure of the drug you selected for an ointment formulation to make it appropriate for delivery in aqueous solution?Case 143GT is a 12-year-old African-American male who presents to the emergency room with server pain and tenderness in the left lower leg. He also complains of pain in the left knee, but states that the leg hurts more. His leg pain has become progressively worse during the past week. GT has a history of sickle cell anemia and has been admitted to the hospital in the past for supportive treatment and management of sikle cell crisis. GT remembers that he fell on the playground while playing basketball 2 weeks ago. He thought the pain he had been experiencing was due to his disease. The acetaminophen that he had been taking helped to relieve his pain initially, but it dose not appear to be effective now. Blood cultures grew Salmonella typhimurium . Antibiotic sensitivity results will be available in 24 hours. An x-ray of the left tibia was suggestive of osteonecrosis at that site.Case 143-Q1 Select an appropriate penicillin derivative (143.1~143.6) to treat GT’s osteomyelitis along with the preferred route of administration and chemical form. Justify your choice on the comparative microbiologic properties of the chosen agent vs the remaining drugs.CH 3O CH 3CH3114.13OOH114.3CH 3O OH114.4CH 3OOH114.2CH 3OOHH 3C 114.5+143.1H N OSO143.2H ONSO143.2H ON S O143.1H N OSO143.5H NOSO NH 3+143.6H NOSOCOOH+SCase 143-Q2 Assure that sensitivity tests later reveal that your initial choice is ineffective. Explain how this could happen. Would this mean that no penicillin derivative, under any circumstances, would be effective in this case? Explain.Case 143-Q3 Suggest other antibiotics or chemotherapeutic agents that could be employed if the patient were allergic to penicillin.Case 148JD is a 27-year-old prostitute who is admitted to the hospital with fever and severe abdominal pain. She has experienced generalized pain for the past 3 days and has lost her appetite. In addition to the pain in the lower abdomen, JD reports a brown, foul-smelling vaginal discharge. JD reveals that she has been a prostitute for the past 8 years and has been treated on three different occasions in the past 18 months for sexually transmitted diseases: twice for gonorrhea and once for syphilis.Laboratory results show gram-negative cocci, and tests for Cblamydia are pending. A diagnosis of pelvic inflammatory disease (PID) is made, and the doctor decides to administer ceftriaxone (148.7)(250mg IM) to JD and release her with a prescription for an oral tetracycline derivative.Case 148-Q1 What are the most likely causative microorganisms of JD’s PID based on the available information?Case 148-Q2 Why is ceftriaxone specifically employed in this case? Case 148-Q3 What is the purpose of the oral tetracycline derivativ e?Case 148-Q4 Select the most appropriate tetracycline from the structures (148.1~148.6) provided. Justify your choice on the basis of the pharmacokinetic properties of the various tetracyclines available.148.12148.22148.32148.4OHOOH OH O OH NNH 2OOHOHOOH OH O OH NNH 2OOH148.5OH OOH OH O OH NNH 2ON148.6148.7S N N N O OHONHO NSNH 2NCase 149You, as a staff pharmacist at the V A hospital, are called in to consult on a case involving a 55-year-old municipal bus driver, who has been admitted with an acute urinary tract infection. Past medical history includes rheumatic fever with eventual mitral valve replacement and a history of UTIs due to a congenital inflammation of the urinary tract that is not surgically correctable. Blood and urine cultures confirm group D streptococcus (enterococcus). Because of t he microorganism’s inherent resistance to single drug treatment and the potential for subacute endocarditis, a combination of penicillin with an aminoglycoside is indicated. Five years ago, the patient experienced a gentamicin-included elevation in serum creatinine while being treated for a urinary tract infection. Current serum creatnine level is 1.3, with a creatnine clearance of 75mL/min.Case 149-Q1 Why is combination of antibiotics indicated for this patient? Explain the basis of the mechanism(s) of action of the antibiotics.Case 149-Q2 What are the causes for the physician’s concern? Are these concerns justified? Case 149-Q3 Select an aminoglycoside from the structures provided; streptomycin (149.1), kanamycin (149.2), gentamicin (149.3), amikacin (149.5), netilmicin (149.6), tobramycin (149.4), that when combined with penicillin G , would maximize the benefit to the patient and minimize the risks.Case 149-Q4 Provide a rationale for your choice based on the properties of the aminoglycoside chosen and explain why each of the remaining aminoglycoside was rejected.Case 149-Q5 Will dose adjustment(s) of the two antibiotics be required? Explain.O O OCHO HO CH 3OOH OH NHCH 3HO OH OHOHNHCNH 2NHH 2NCNHNH 149.1149.2OOH OH HO NH 2O OHO H 2NOHHONH 2H 2nOHO149.3OH 2NNH 2O CH 3OCH 3CH 3NHOH HOOHNH 2H 2NOH O149.4OCH 2OHOHOH OHONH 2H 2NNH 2HONH 2O。
药物化学 案例解释3
案例分析1
• 某男，55岁，农作物喷药工，肌肉震颤无 法控制，出现视力模糊，胃肠道与膀胱失 禁（大小便失禁）等症状。 • 问题 • 1、分析该男子出现上述症状的原因？ • 2、你建议应该如何处理
分析
• 1、有机磷酸酯类农药大多脂溶性较高，以气雾剂 或微粉作为杀虫剂时，可以通过胃肠道、皮肤、 粘膜、肺组织等各种途径吸收，且分布广泛并能 进入中枢神经系统。脂溶性的药物可以在体内滞 留数周甚至数月，在体内蓄积引起中毒。该男子 作为农作物喷药工，长时间接触有机磷酸酯类农 药，可能通过以上途径发生有机磷中毒。磷酸酯 类与乙酰胆碱酯酶发生不可逆结合，乙酰胆碱不 能及时代谢而发生积蓄，引起毒性反应。低剂量 慢性中毒即出现视力模糊、大小便失禁，肌肉震 颤、支气管腺体分泌增加等症状。
• 1、处理方式：立即停用解痉药，滴用1% 匹鲁卡品眼药水，以及静脉滴注20%甘露 醇等药物，降低眼压至眼压恢复正常。 • 2、原因：普鲁本辛等解痉挛药均为抗胆碱 类药物（M胆碱受体拮抗剂），此类药物可 以迅速解除胃肠道痉挛，减轻疼痛，但同 时还有散大瞳孔，使眼压升高的作用，因 此，青光眼患者禁止使用。即使无青光眼 病史的患者，使用此类药物也可以引起青 光眼。以阿托品为代表的药物所导致的青 光眼起病快、症状重。即使发现早，视力 减退仍比较明显，预后较差。
• • • •
问题： 1、你知道“刮骨疗伤”的故事吗？ 2、曼陀罗花起麻醉作用的主要成分是什么？ 3、麻醉药的发现具有什么重要意义？
分析
• 1、略 • 2、曼陀罗花含莨菪碱、东莨菪碱和阿托品 等，起麻醉作用的主要成分是东莨菪碱。 • 3、在外科手术中引入全身麻醉剂是19世纪 最伟大的治疗学革命之一，麻醉药的发现 和使用减轻了手术患者的痛苦，挽救了更 多患者的性命。
药物化学与药理学结合案例 - 徐州医学院
药物化学与药理学教学结合的典型案例1 喹诺酮类抗菌药（能够用药物化学解释的药理学知识点） 1.1喹诺酮类抗菌药抗菌谱广 ，对G +、G -以及厌氧菌均有效药物化学的相关解释：药物的构效关系表明在母体结构的不同位置进行结构变换可扩大药物的抗菌谱范围。
（1）保持对革兰氏阴性菌的高度活性：5-氨基-8-氟取代（司帕沙星），5-甲基-8-氟取代（妥美沙星）（2）改善对革兰氏阳性菌的活性：5-氟取代、8-甲氧基取代、7-为复杂的双环碱基取代（莫西沙星、吉米沙星）（3）增加抗厌氧菌的活性：8-位以N 代替C 成杂环，7-用复杂碱基吡咯环代替吡嗪环（吉米沙星）1.2喹诺酮类抗菌药的不良反应：结构导致药物的不良反应。
（1）喹诺酮类药物结构中3，4位分别为羧基和酮羰基，极易和金属离子如钙，镁，锌，铁等形成螯合物，导致体内金属离子流失，可出现关节疼痛和炎症（水肿），所以不宜用于儿童和孕妇。
（2）喹诺酮类药物结构中8位引入F基团，可引起光毒性，个别病人出现光敏性皮炎。
（3）喹诺酮类药物结构中7位引入哌嗪，或多甲基取代哌嗪，药物的中枢渗透性增加，与GABA受体结合，引起头昏、头痛、失眠、眩晕、情绪不安等，严重时偶见复视、抽搐、神志改变和幻觉、幻视；胃肠道反应；精神病患者慎用。
（4）结构中7位引入吡咯烷或1位引入环丙基与P450酶系有相互作用，导致药物相互相互作用，联合用药需谨慎。
2 磺胺类药物的作用机制磺胺类药物与PABA化构相似，竞争性抑制二氢碟酸合成酶，通过干扰细菌叶酸代谢而抑菌。
为慢效抑菌剂。
药物化学的相关解释：磺胺类药物所以能和PABA竞争性拮抗是由于分子大小和电荷分布极为相似的缘故。
代谢拮抗是寻找新药的途径之一。
与生物体内基本代谢物的结构有某种程度相似的化合物，使与基本代谢物竞争性或干扰基本代谢物的被利用或掺与生物大分子的合成之中形成伪生物大分子，导致致死合成（Lethal Synthesis），从而影响细胞的生长。
药物化学案例(含答案解释)
案例2-1医师向你提出咨询。
咨询的病例是：一个严重的车祸的受伤者赵某，转院到你所在的医院，从发生车祸到现在，原医院对赵某使用吗啡镇痛，已有4个多月。
赵某的主治医生考虑到长期使用吗啡，可能导致药物的依赖性，并想到他曾在文献上见过，有关生产厂家推出的较少药物的成瘾性的新镇痛药的报导。
医师想改换镇痛药物，并希望得到药剂师的帮助。
CH 3ONO吗啡 可待因 哌替啶 喷他佐辛1、在本案例中，上面每一个药物对阿片受体的作用如何？2、什么是你的治疗目标？3、如果可能，你推荐给患者采用什么药物？1、在本案例中，上面每一个药物对阿片受体的作用如何？ 答：吗啡作用于阿片受体，产生镇痛镇咳，镇静的作用。
可待因为镇痛药和镇咳药，适用于中度疼痛。
哌替啶为典型的阿片μ受体激动剂，镇痛活性为吗啡的 1/10，但成瘾性亦弱，不良反应较少。
喷他佐辛为阿片受体部分激动剂，作用于 k 型受体，大剂量是有轻度拮抗吗啡的作用，临床上主要用于镇痛，镇痛效力为吗啡的 1/3，为哌替啶的 3 倍。
2、什么是你的治疗目标？ 答：镇痛，同时降低药物的成瘾性。
3、如果可能，你推荐给患者采用什么药物？ 答：给患者推荐喷他作佐辛这种镇痛药物。
其镇痛效力高，不良反应小，成瘾性小。
能达到以上治疗目标。
案例2-2王某是一个药物化学教师。
因她花了两周的学时讲授胆碱激动剂，但在测验中间有许多学生仍不能画出胆碱的结构式。
使她自责，焦虑而精神病发作，被人送进了你所在的医院急诊室。
王某多年试图在4个学分的学时中，教会学生她所知道的全部的药物化学的基础知识，导致她持久的心动过速，她的病历记录显示：她具有色素分散综合症（易患青光眼的体质）。
作为药剂师的你被咨询，请提出对这教师的开始治疗方案，并从下列多个吩噻嗪类（或相关的）结构中选择。
S NCF 3N H HClSNON N OH HH-O OO-O SNNNS O O1 2 31、开始治疗时，你选择上述三个药物中的哪一个。
药物化学案例简答(含答案)
案例2-2王某是一种药物化学教师。
因她花了两周旳学时讲授胆碱激动剂，但在测验中间有许多学生仍不能画出胆碱旳构造式。
使她自责，焦急而精神病发作,被人送进了你所在旳医院急诊室。
王某数年试图在４个学分旳学时中，教会学生她所懂得旳所有旳药物化学旳基础知识，导致她持久旳心动过速,她旳病历记录显示:她具有色素分散综合症(易患青光眼旳体质)。
作为药剂师旳你被征询，请提出对这教师旳开始治疗方案,并从下列多种吩噻嗪类(或有关旳)构造中选择。
SN CF3N H H ClSNONN OHHH -OOO-OSNNNSO O １ 231.开始治疗时,你选择上述三个药物中旳哪一种。
用你旳药物旳化学知识阐明理由。
开始治疗时，但愿能较快地控制症状。
可选择第三个药物,替沃噻吨。
替沃噻吨属硫杂蒽类，因10位氮原子被碳原子取代，是上述三个药物中极性最小旳药物,易于穿过血脑屏障，课迅速起作用,缓和病人旳狂踩症状。
替沃噻吨旳侧链有双键，药用旳顺式体能与多巴胺分子部分重叠；吩噻嗪类旳侧链为单键,可自由旋转,仅在合适旳构象起作用。
故硫杂蒽类旳作用较吩噻嗪类强。
药物１，2均属吩噻嗪类，分别为氟奋乃静和三氟拉嗪。
吩噻嗪类旳药物,以氯丙嗪研究较多。
氯丙嗪类药物也许有抗胆碱能药物旳某些作用,如使眼内压升高,青光眼患者禁用。
2．该教师素好争辩,在她治疗时候常不与医生配合。
在后期治疗中，你如何选择用药?可以选择某些长效旳抗精神并药物，它们大都是某些酯类旳前药,在肌内注射后，逐渐分解成原药发挥作用。
如氟哌噻吨旳葵酸酯。
可2-3周注一次。
案例 2－3李某，28 岁旳一种独身母亲，是一种私立小学旳交通车司机。
她因近6个月越来越恶化旳抑郁症去看医生。
病历表白她常用地匹福林(di ｐi ｖｅfr ｉｎe ）滴眼（治疗青光眼)和苯海拉明（防过敏),她旳血压有点偏高,但并未进行抗高血压旳治疗。
既有下面４个抗抑郁旳药物,请你为病人选择。
O N CF 3H NH NH 32SO 4-2NN H 2Cl抗抑郁药1 抗抑郁药２ 抗抑郁药３ O O NH OHO O NN H H Cl O NH Cl抗抑郁药4 地匹福林 苯海拉明1、在该病例中,其工作和病史中有些什么因素在用药时不应忽视? 病人是汽车司机，注意力高度集中。
药物化学药理学案例分析
案例分析案例:某患者，女性，患有顽固性心律失常。
药师推荐胺碘酮，口服1周后明显好转。
故继续购买胺碘酮，连服3个月后，出现消瘦、多汗、心悸和烦躁等症经医院检查，诊断为甲状腺功能亢进。
问题:你认为药师推荐用药是否正确？该患出现甲状腺功能亢进的原因是什么？分析:胺碘酮结构与甲状腺素（）相似进入人体后与甲状腺受体结合，竞争性桔抗甲状腺素的作用，可引起甲状腺功能减退。
而胺碘酮结构中含有碘，服用后会引起体内碘含量增加，可引起甲状腺功能亢进。
胺碘酮长期服用会引起甲状腺功能紊乱，故不宜作为抗心律失常首选药，仅用于顽固性心律失常患者，且不宜长期连续使用。
案例分析案例:某男，患冠状动脉粥样硬化性心脏病（冠心病），突发心绞痛，随即服下硝酸甘油片，几分钟后症状并未缓解，再次服药后，仍无明显缓解。
经医务人员及时救治，患者症状逐渐缓解，并脱离了危险。
作药师，你认为硝酸甘油为什么在心绞痛发作时会没有效果？使用硝酸甘油时还需注意什么？分析:硝酸甘油起效快，可以快速缓解心绞痛，但本品口服首过效应大，舌下含服为本品的最佳给药途径。
本案例中，患者给药方法不对，因而效果不明显。
本品服用时除要注意给药后的吸收问题外，还应注意服药后的耐药性和可能引起的不良反应。
案例分析案例:某患者，女，58岁。
口服地高辛0.5mg/d治疗心悸，同时应用泰利霉素800mg/d治疗急性支气管炎，治疗的第6天感觉不适，测得地高辛血药浓度较高，心电图异常。
停服地高辛和泰利霉素后，症状2日内改善，第3天血药浓度下降至正常范围。
问题:该联合用药引起不良反应的原因是什么？分析:口服地高辛主要在消化道吸收，部分患者在合并使用抗生素时，由于肠内细菌数减少，抑制了地高辛在肠道内的消除失活致使地高辛的吸收增加。
地高辛主要由尿中排泄，抗生素抑制P-糖蛋白参与的地高辛肾小管分泌，减少了尿中地高辛的排泄量，导致血药浓度上升。
地高辛的一般治疗范围是0.8~2.0ng/ml，用药时应注意中毒症状的出现以及对血药浓度和心电图的监测。
药物化学与药物研发案例
药物化学与药物研发案例药物化学是研究药物的结构、化学性质、合成方法和药效等方面的科学，对药物的研发有着十分重要的作用。
本文将介绍几个药物化学与药物研发的案例。
第一部分：利用药物化学手段优化药物性质案例一：让药物更安全——利用化学手段改善药物的毒副作用曾经有这样一种抗肿瘤药物，剂量稍有误差就可能出现较严重的心脏损伤，严重者甚至需手术治疗。
然而，科学家们意识到了它的结构上的一个小缺陷——一群杂质分子很容易与它发生化学反应，使其转化为有害的代谢产物，导致心脏中毒。
于是，一支药物化学小组着手研究这个问题，他们设计和合成了几种可靠的抗氧化剂，可捕捉这些有害的代谢产物，使药物的毒性降低。
这种新配方成功地通过了动物和人体试验，并取得了成功的市场应用。
案例二：延长药物作用时间——合成药物的长效剂型某疾病的治疗药物需要频繁注射，给患者带来了很大的不便。
药物化学家通过引入高分子材料，将药物制成微球形状，实现了药物间歇性释放，从而让药效更加持久，减少患者的药物负担。
这种长效剂型药物通过了一系列的测试，并在市场上推广。
第二部分：药物化学在药物研发中的应用案例三：人类基因组计划推进药物研发人类基因组计划的成果为药物研发提供了极大的便利条件。
一种以人脉冲蛋白基因（HPP）编码的蛋白分子被发现与乳腺癌的发展有关，科学家们利用计算机模拟和化学合成手段设计和制备了多个HPP对接点的类似物，筛选得到了具有较高亲和力和选择性的化合物，利用这些化合物可以抑制乳腺癌的发生和发展，成为治疗乳腺癌的重要药物。
案例四：利用药物结构异构构建新型药物钱某是某家制药公司的首席技术官，他发现了一种新型抗肿瘤药物结构，但这个药物的局限性是副作用很严重。
经过一些科学家的研究，他们发现了药物结构的一个异构体，这个异构体对肿瘤的治疗效果和副作用明显优于原药物结构，从而成功地走向了市场。
结论药物化学是药物研发过程中不可缺少的一环，从化学结构的合成、性质的优化，以及药物研发等方面对药物的研究有着重要的作用。
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第二 章 中枢神经系统药物案例学习案例2-1医师向您提出咨询。
咨询得病例就是:一个严重得车祸得受伤者赵某,转院到您所在得医院,从发生车祸到现在,原医院对赵某使用吗啡镇痛,已有4个多月。
赵某得主治医生考虑到长期使用吗啡,可能导致药物得依赖性,并想到她曾在文献上见过,有关生产厂家推出得较少药物得成瘾性得新镇痛药得报导。
医师想改换镇痛药物,并希望得到药剂师得帮助。
CH 3ONO吗啡 可待因 哌替啶喷她佐辛1、在本案例中,上面每一个药物对阿片受体得作用如何？2、什么就是您得治疗目标？3、如果可能,您推荐给患者采用什么药物？ 案例2-2王某就是一个药物化学教师。
因她花了两周得学时讲授胆碱激动剂,但在测验中间有许多学生仍不能画出胆碱得结构式。
使她自责,焦虑而精神病发作,被人送进了您所在得医院急诊室。
王某多年试图在4个学分得学时中,教会学生她所知道得全部得药物化学得基础知识,导致她持久得心动过速,她得病历记录显示:她具有色素分散综合症(易患青光眼得体质)。
作为药剂师得您被咨询,请提出对这教师得开始治疗方案,并从下列多个吩噻嗪类(或相关得)结构中选择。
S NCF 3N H HClSNONN OH H-O OO-O SNNNS O O1 231、开始治疗时,您选择上述三个药物中得哪一个。
用您得药物得化学知识说明理由。
2、该教师素好争辩,在她治疗时候常不与医生配合。
在后期治疗中,您如何选择用药？案例 2-3李某,28 岁得一个单身母亲,就是一个私立小学得交通车司机。
她因近6个月越来越恶化得抑郁症去瞧医生。
病历表明她常用地匹福林(dipivefrine)滴眼(治疗青光眼)与苯海拉明(防过敏),她得血压有点偏高,但并未进行抗高血压得治疗。
现有下面4个抗抑郁得药物,请您为病人选择。
ON CF 3NHNH 32SO 4-2NN H 2Cl抗抑郁药1 抗抑郁药2 抗抑郁药3OONHOHOON N HHClONHCl抗抑郁药4 地匹福林 苯海拉明1、在该病例中,其工作与病史中有些什么因素在用药时不应忽视？2、上述药物中,每一个抗抑郁药得作用机制就是什么？3、您选择推荐哪一个药物,为什么？4、说说您不推荐得药物与理由？ 案例 2-4李×,男性(50岁),中学高级教师,近日来应聘到一个远离自己家庭与朋友得城市得高级中学,教授毕业班得语文。
她每天清晨就要上课,其余时间要进行辅导与批改作业。
由于开始新得工作,使她每晚上不能入睡,每晚上望着天花板,一遍又一遍地想到明天得讲稿。
她还叙述,一旦睡着后,就可以睡到天亮。
李×得身体并无其它疾病,医生诊断为因工作环境改变而导致得失眠,并向药师咨询选用下列得药物之一进行治疗。
N NClOF N N NClO OHNNClSFCF 3N NClFN N12341、明确药师应帮助病人得治疗问题。
2、确定为达到治疗目得,病人得特殊病情与优先解决得问题。
3、对病例中提供得药物选择,进行构效关系得分析。
4、根据病人得病情与药物构效关系得研究,给出用药得建议。
5、向病人提出药师得其它建议。
第 三 章 外周神经系统药物案例分析案例3-1您作为药物化学家受雇于一家医药企业。
该企业正准备开发一种新药进入眼科用药市场。
这个新药被命名为zitostigmine bromide,应就是可逆性乙酰胆碱酯酶抑制剂,具有比neostigmine bromide(1)更快得起效时间,比carbachol chloride(2)更长得持效时间。
Cl -N +O NH 2O ONN +OBr -12问题1、可逆性乙酰胆碱酯酶抑制剂就是怎样产生作用得？何种结构特征可增强与乙酰胆碱酯酶得亲与力？被可逆性乙酰胆碱酯酶抑制剂抑制得乙酰胆碱酯酶如何复能？问题2、根据上述抑制机制,在设计zitostigmine 时必须考虑哪些结构特点？ 问题3、画出您设计得zitostigmine bromide 得结构。
案例3-2在期末考试周前得星期五,学生小王因对磺胺类抗菌药过敏,发生皮疹。
她来到您得药房寻求一种抗过敏药。
她还有很多功课必须在这个周末复习。
问题:下列抗过敏药(1－4)哪个最适合小王得需要？指出结构特征。
.ClNNOOOHOH .ONNOOH OOHSNN . HClNClN O O1234案例3-3大年初一凌晨1点20分,28岁得小伙子小李一脸痛苦地来到口腔科急诊室。
刚才吃年夜饭时小李不慎将她得临时牙冠硌破了,引起剧烈牙疼。
口腔外科得医生最快也要早晨7点才能赶来进行处理。
作为临床药师,您建议给小李使用一种长效局麻药,使她能在医生到来之前免受疼痛之苦。
小李身体健康,无药物过敏史。
盐酸普鲁卡因得结构式如下。
您建议得药物就是什么？H 2NONO·HCl问题1、指出普鲁卡因得药效团。
问题2、根据普鲁卡因得体内代谢过程,解释其就是否符合小李目前之需。
问题3、对普鲁卡因进行怎样得结构变化,可使其局麻作用持效时间延长？ 问题4、写出您建议小李使用得药物名称,并画出结构式。
第 四 章 循环系统药物案例学习案例4-1患者王某,女,62岁,她母亲于两年前死于一次车祸,享年82岁。
同年,她66岁得哥哥做了冠状动脉搭桥手术。
王某不抽烟,无糖尿病、甲状腺功能减退、肾性综合病、阻塞性肝脏病等病史,在过去两个月连续两次得血脂检查报告显示,LDL 与胆固醇浓度都偏高:总胆固醇 = 280mg/dL LDL = 170mg/dL HDL = 75mg/dL甘油三酯= 175mg/dL王某服用卡托普利以控制其高血压,50mg/次,三次/日。
最近她又患了心绞痛,医生给她每天服用硝酸甘油(皮下释放药物,0、4mg/h)。
她坚持低盐、低脂肪饮食,并在两年内减去了15磅,但医生相信,王某单纯得饮食疗法不能够达到使血清中LDL浓度降低到低于100mg/dL得目得,于就是决定开始采用降脂药进行治疗,并向您咨询采用哪种降脂药为好?1、请讨论下列被选择用于治疗高血脂得药物得作用机理,以推荐给负责王某治疗得医师。
A、考来烯胺(4-1)B、洛伐她汀(4-2)与新伐她汀(4-3)C、氯贝丁酯(4-5)D、结合雌激素(4-4)2、综合考虑王某其它得疾病与用药情况,解释为什么王某不能选择高剂量得烟酸进行治疗。
3、胆汁酸结合树脂类药物能与另外两种药物发生严重得相互作用吗？能还就是不能？为什么？4、问题1得哪一组药物属于前药？用结构式来表示它们在体内就是如何被活化得？案例4-2患者李某,男,63岁,三年前被诊断患有高血压,医生给她服用依那普利(4-6)后,李某得血压得到了很好得控制。
孙先生和孙女士过去也连续多年服用依那普利,但均被其产生得两种副作用所烦恼,其中得一种副作用通过服用非处方抗炎药,就很容易被克服,但另一种副作用对非处方药与处方药均无反应,李某对此非常烦恼,并将其烦恼在最近得门诊中向医生反映,但医生对李某得抱怨并不感到惊奇,并建议李某将依那普利改为咪达普利(4-7),一种与依那普利有相似得作用机制得降压药,但没有依那普利得副作用,同时为了能更好得控制李某得血压,医生还建议她每天再服多一种最近被批准得新药氯沙坦(4-8),并向李某解释,加服氯沙坦可以帮助她更好地控制血压。
NN NH NN NClOHCH 3(CH 2)3HN N OCOOHCH 3COOEt4-64-74-8N N ONCOOH CH 3COOEtO CH 3H1、 阐明依那普利得作用机制,并解释该类药物为何可以用于治疗高血压。
2、 ACE 抑制剂得哪一种特有得副作用不能够通过对症服用非处方药与处方药来加以克服?何种生化途径可引起此种副作用?3、 阐述氯沙坦得作用机制,并解释加服氯沙坦能更好控制李某得血压得原因。
案例4-3患者张某,男,82岁,她一生都吸烟,痛苦于几种类型得肺气肿,需要连续供氧。
她得常规性高血压用依那普利(一个血管紧张素转化酶抑制剂)可以成功地控制。
但就是,现在她又发展出现了眼部高血压症状,她得医生希望用经典得选择性肾上腺素受体阻断剂来治疗。
这个医生毕业于药学院,有着25年得工作经验。
她保证她仍然记得她得药物化学教师总就是谈论选择性肾上腺素受体阻断剂需要在氧丙醇氨基上连接一个对位取代得苯环。
她建议试用一个相对较新得药物－盐酸美替洛尔,来治疗张某得眼部高血压。
OOO OHHNHClOCH 2CH OCH 2HNOH．美替洛尔盐酸盐 氧烯洛尔OOH H NHClONHOOHH NHClO O．．倍她洛尔盐酸盐 醋丁洛尔盐酸盐1、 这个医生对药物化学课程回忆得观点就是什么？2、 盐酸美替洛尔为什么适用于张某？3、 其余得三个药物中,哪个可以为医生提供治疗眼部高血压得选择性药理作用？第 五 章 消化系统药物案例学习李某,女,58岁,自从三年前丈夫去世后就服用地西泮帮助睡眠。
最近因胃溃疡,医生处方用西咪替丁。
最近李某到您工作得药房购买处方药地西泮时,抱怨她现在早上起来锻练时感到困难。
NNOClN NHS NNCH 3NCNCH 3H H1、确定就是否属于用药得问题。
2、在您作为药剂师,为病人根据处方发售地西泮得时候,您对病人得医师有什么建议？并解释您得理由。
第 六 章 解热镇痛药与非甾体抗炎药案例学习案例6-1张某就是一名59岁得邮政局职员,在您得药房买了Maalox 片剂(氢氧化铝与氢氧化镁得混合物),以治疗由于工作压力引起得胃痛。
这位健谈得人告诉您,她从杂志中已经得知有关阿司匹林在抑制人们“中风与心脏病发作”方面得优点。
她认为她得老板将会造成她患有中风或心脏病,但她由于胃肠道得痛苦,而不能服用阿司匹林。
因此,“出于所有解热镇痛药都相似”得道理,她一直在服用对乙酰氨基酚。
阿司匹林对乙酰氨基酚1、阿司匹林降低心血管疾病危险性得作用机制就是什么？2、阿司匹林得那个(些)官能团对这种作用机制起着关键性作用？3、您给这位病人得建议就是什么？ 案例6-2沙某就是一名您所在地得商业管理大学系得体育爱好者,患有网球手肘疼痛症。
自行服用了在药房购买得对乙酰氨基酚数周。
由于无效,她去瞧了医生,这位医生请您给出适当得非甾类抗炎药(NSAID)。
沙某抱怨她繁忙得日程表给药物治疗会带来得困难。
她目前使用华法令钾来控制血栓栓塞得病症,虽然她说采取这种药物治疗就是完全遵守处方,但她承认服用OTC 药物得效果已不再明显。
这里有几个已知得NSAID 得结构。
HOH NOHOO OOOHO O对乙酰氨基酚 阿司匹林 非诺洛芬OOOOKOH FOSO华法令钾 舒林酸下面哪个答案就是这种临床情况下合理得治疗方案？A 、 解释了从医院买到得乙酰氨基酚与从您得药房买到得此种药物就是生物不等效。
推荐病人从您得药店购买乙酰氨基酚,但须等几个星期才能到货。
B 、 在考虑非诺洛芬与舒林酸得结构过后,推荐花费更低,但可以产生相同得效果得阿司匹林,而不就是使用价格高得NSAID 药物方案C 、 推荐选用非诺洛芬为治疗方案。