药物化学案例研究(英文版)CASE STUDY for 10

CASE STUDY

Medicinal Chemistry

Case 1

A 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 3

A 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 why

not?

Case 5

ZT, 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 N

N

O

O

ONa pKa = 8.0

Case 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?

, HCl

O

NH

Case 17

You 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?

17.1S

NH2

H2N O O

H

17.3

S

N

H2N

O O

N

N

H

17.4

S

N

H2N O O O

H

17.5

S

N

H2N

O O

Case 28

LP, 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 taking