PCL201H1 Lecture : Lecture 25 Adverse Drug Reactions

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azuresquirrel208

22 Apr 2012

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Drug use in pregnancy: drug effects in pregnancy rarely evaluated befre market release, use not recommended unless benefits justify risk. Types of malformations: major: structural/functional defects, medical/surgical intervention necessary, incompatible with life, impair individuals" capability to function normally in society, minor: unusual morphological traits, no serious medical/cosmetic consequences to child. Thalidomide: antiemetic during pregnancy, limb reduction defect, other abnormalities, critical period of exposure 45-50 days after first day of last menstrual period. Direct effects of drugs on fetus (cellular: receptor-mediated toxicity: relatively predictable/proportional to drug concentration, reactive intermediate mediated toxicity, proteratogens biotransformed to electrophiles, free radicals target dna, proteins, lipids. Indirect effects of drug on fetus (maternal effects: poor nutrition, disease states, altered blood supply to fetus. Effects on fetus/infant: malformation, disruption, deformation, fetal loss, fetal toxicity/withdrawal, neurodevelopment (cognition/behavior, long term effects (carcinogenesis/mutagenesis) Heavy alcohol exposure: fas (fetal alcohol syndrome, ethanol growth retardation, mental retardation, neurobehavioral deficits, facial dysmorphia, dose-dependent, ranges in frequency and severity.

Related Questions

3.a) (S)-(+)-propranolol is used to treat heart disease. Its enantiomer, (R)-(-)-propranolol, has contraceptive properties. Draw the (S) form (please draw the whole molecule). Number the substituents on the chiral center in order of priority.

3.b) In the 1950s and 1960s, racemic thalidomide was prescribed to alleviate morning sickness during pregnancy. It was later learned that only one enantiomer, the (R) form, has the desired anti-emetic effects and the (S) form is a teratogen, causing birth defects. Draw the (R) enantiomer.

3.c) It turns out that, even if only the (R) enantiomer of thalidomide is taken, it racemizes under physiological conditions. Draw the form(s) of thalidomide found in the body after the racemization process.

As the hospital epidemiologist you are asked to investigate theeffect of a drug suspected of causing malformations in newborninfants when the drug in question is taken by pregnant women duringthe course of their pregnancies. As your sample you will use thenext 200 single births occurring in a given hospital. For eachbirth a medication history will be taken from the new mother andfrom her doctor; in addition, you will review medical records toverify use of the drug. [N.B.: These mothers are considered to havebeen followed prospectively during the entire course of theirpregnancies, because a complete and accurate record of drug use wasmaintained during pregnancy.]

The resultant data are:
Forty mothers have taken the suspected drug during theirpregnancies. Of these mothers, 35 have delivered malformed infants.In addition, 10 other infants are born with malfunctions.
The relative risk between exposure to the drug and malformationsis
A.16
B. 12
C.14
D. 10
E. 15

blushgoldfish745

Thalidomide achieved notoriety 50 years ago because of a wave of birth defects among children born to women who took this drug during pregnancy as a treatment for morning sickness. Thalidomide is a mixture of two enantiomers; one reduces morning sickness, but the other causes severe birth defects. The U.S. Food and Drug Administration withheld approval of thalidomide in 1960. Since then, however, the FDA has approved this drug for the treatment of conditions associated with leprosy and newly diagnosed multiple myeloma, a blood and bone marrow cancer. Assuming that molecules related to thalidomide could be synthesized in the laboratory, describe in a broad way the type of experiments you would do to improve the benefits of this drug and minimize its harmful effects.

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PCL201H1 Lecture : Lecture 25 Adverse Drug Reactions

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