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1. Describe teratogenicity.
a. Teratogenicity refers to a drug or substance that causes harm to fetal development when the mother is exposed to it. Some features of teratogens include producing a similar pattern of malformation in different patients and having effects during the same gestational time across cases.
2. List examples of drugs with a known potential to cause adverse fetal effects when taken by pregnant women.
a. ACE inhibitors: renal malformations
b. Cyclophosphamide: various congenital malformations
c. Ethanol: Fetal alcohol syndrome
d. Heroin: neonatal dependence
e. Mycophenolate mofetil: face, limbs, other malformations
f. Tetracycline: discoloration/defects of teeth, altered bone growth
g. Thalidomide: limb defects
h. Warfarin: different defects at different times during pregnancy
3. List some potential physiological differences between infants and older individuals that can result in pharmacokinetic differences.
a. Increased or decreased oral bioavailability related to differences in gastrointestinal function, such as varied levels of enzymes/bile acids.
b. Differences in distribution related to differences in body water and protein binding.
i. There is higher body water as % of body weight in neonates.
c. Slower elimination of many drugs in neonates due to lower activities of P450 enzymes and conjugating enzymes in neonate.
d. Lower renal clearance of some drugs in neonates due to lower GFR.
4. List examples of drugs with a known potential to cause adverse effects in breast feeding infants when taken by the mother.
a. Chloral hydrate: drowsiness
b. Chloramphenicol: bone marrow suppression
c. Diazepam: sedation
d. Heroin: prolong neonatal dependence.
e. Codeine in rapid metabolizers (codeine is partially metabolized to morphine).
5. Describe the age-related differences in body water and fat composition that can affect drug distribution
a. Elderly individuals have decreased total body water and increased body fat (as % of body mass), which may lead to altered distribution of some drugs.
6. Describe other potential physiological differences between elderly patients and younger adults that can result in pharmacokinetic differences.
a. About 2/3 of elderly individuals have decreased creatinine clearance, which is related an increased half-life of some drugs (i.e. those eliminated by renal excretion).
b. Elderly individuals may have decreased hepatic clearance of some drugs related to decreased rate of hepatic metabolism. The change in phase I reactions (cytochrome P450) is greater than the change in phase II reactions.
7. Describe some drugs used for their effects on the ductus arteriosus.
a. Indomethacin (an NSAID) is used for the closure of a patent ductus arteriosus in certain premature infants. The mechanism is probably related to decreased prostaglandin synthesis.
b. Prostaglandin E1 is used to maintain the patency of the ductus arteriosus in certain neonates with congenital heart defects.
8. Describe some drugs used in the management of Alzheimer’s disease.
a. Acetylcholinesterase inhibitors such as denepezil.
b. NMDA receptor antagonists such as memantine. (NMDA receptors are stimulated by glutamate).
9. Describe some drugs used in the management of neovascular (wet) age-related macular degeneration.
a. Ranibizumab – monoclonal antibody fragment that binds VEGF
b. Pegaptanib – pegylated oligonucleotide that binds VEGF
c. Bother are administered by intravitreal injection.