Lecture 19

Question 1

What role do drugs commonly which may lead them to affect pregnancy?

Answer 1

Up to 30% of women receive some form of drug during pregnancy with it being more common earlier in pregnancy when the child is more susceptible
1:20 Women take a category C or X drug
5% of defects are attributable to drug exposure
The placenta offers variable and incomplete protection

Question 2

What are the different risk categories for drugs taken in pregnancy as established by the FDA?

Answer 2

A. Controlled studies in humans show no risk
B. No risk in animal studies or no risk of suggested by human studies
C. Animal studies indicate a risk but no human studies available
D. Evidence of foetal risk but benefits outweigh the risk
x. Evidence of high risk to foetus which outweigh the benefits

Question 3

What are the classes of anti-epileptics during pregnancy?

Answer 3

Valproate which is a category X and Phenytoin which is a category D

Question 4

What are the classes of antibiotics used during pregnancy?

Answer 4

Mostly category B except for aminoglycosides and tetracyclines

Question 5

What are the things that must be considered in a balance judgement of whether a drug should be taken during pregnancy?

Answer 5

The effects of not giving the drug vs the potential harm to the fetus from drug use

Question 6

What are some of the adverse effects drugs can have on the fetus?

Answer 6

Teratogenicity such as thalidomide
Long term latency from drugs such as diethylstilbestrol
Impaired intellectual or social development from excessive use of alcohol
Predisposition to metabolic disease from things such as smoking

Question 7

What are the classes of antiparasitics used during pregnancy?

Answer 7

Mostly category C except quinine which is category X

Question 8

What is the effect of NSAIDs taken during preganacy?

Answer 8

They are associated with various complications and not recommended in particular during the first and last trimester

Question 9

What is the effect of anti-asthmatic drugs taken during pregnancy?

Answer 9

They are typically not recommended as anti-histamines are known to cause blindness

Question 10

What is the class of diuretics taken during pregnancy?

Answer 10

Mostly category D

Question 11

What is the class of anti-viral drugs taken during pregnancy?

Answer 11

Mostly category C

Question 12

What are the classes of sedatives taken during pregnancy?

Answer 12

Benzodiazepines are Cat D or X

Question 13

What are the changes to the mother that occur during pregnancy which can change the maternal concentration of a drug?

Answer 13

Increase in body fluid volume by 8L
Increased kidney blood flow and GFR by 50%
Decreased gastric motility (30-50% resulting in increased GI transit time)
Nauea and vomiting which can be experienced during pregnancy may also affect the transit time and the pH
Increased cardiac output by 30%
Changes in drug metabolizing enzyme activity as phenytoin metabolism seems to increase while caffeine metabolism decreases

This all typically results in a decreased steady state concentration during pregnancy

Question 14

What are the effects of pregnancy on the renal clearance of drugs?

Answer 14

There is a greater total clearance during pregnancy with a higher % excreted in the urine

Question 15

What does the rate and extent of drug entry into the fetus depend on?

Answer 15

Placental drug transfer occurs mainly through passive diffusion and is controlled by maternal plasma conc, blood flow to placenta, physicochemical properties of the drug, active transporters which may efflux some drugs from the placenta to the maternal circulation

Question 16

What role does the placenta play as a barrier to drug passage into the fetus?

Answer 16

It is not a major barrier to drug passage but does have:
Xenobiotic transporters such as ABC transporters and members of the SLC family of solute transporters
Placental metabolism which largely consists of phase 1 CYP oxidation and phase 2 glucuronidation and sulphation
This metabolism is minor compared to the liver

Question 17

What factors affect fetal drug disposition?

Answer 17

Maternal blood flow to the placenta which increases during gestation
Fetal plasma albumin is 15% greater than maternal but alpha1acid glycoprotein is lower which can affect plasma binding drugs
Fetal plasma pH is lower than the maternal pH which can cause ion trapping and accumaltion of basic drugs in the foetal placenta

Question 18

What is the major route of drug elimination by the fetus?

Answer 18

Placental transfer to the mother and maternal elimination

Question 19

What were the major issues with thalisomide?

Answer 19

Insufficient animal testing before marketing
Chronic toxicity studies were never carried out
Stability and nature of decomposition/metabolism products was never characterized

Question 20

What did later studies of thalidomide demonstrate?

Answer 20

There was a species and strain specificity of thalidomides teratogencity
There was difference in the time the drug was administered
Research in rabbits has suggested that a metabolite formed in the placenta may be responsible for the teratogenic effects