Lecture 15 - Drugs in Pregnancy

Question 1

Changes in Pregnancy:

Creatinine clearance

Answer 1

increases

Question 2

Changes in Pregnancy:

Drug metabolism

Answer 2

variable

Question 3

Changes in Pregnancy:

Most protein binding

Answer 3

increases

*albumin binding decreases

Question 4

Changes in Pregnancy:

gastric emptying

Answer 4

decreases

Question 5

Changes in Pregnancy:

plasma volume

Answer 5

increases by 50%

Question 6

Changes in Pregnancy:

Absorption from skin

Answer 6

increases (increased vascularity)

Question 7

Changes in Pregnancy:

cardiac output

Answer 7

increases by a lot

Question 8

Changes in Pregnancy:

peripheral resistance

Answer 8

decreases

Question 9

Changes in Pregnancy:

diastolic BP

Answer 9

decreases

Question 10

Changes in Pregnancy:

pulmonary resistance MV

Answer 10

increases

Question 11

Changes in Pregnancy:

colloid oncotic pressure

Answer 11

decreases

Question 12

Changes in Pregnancy:

pH in blood

Answer 12

increases

Question 13

Changes in Pregnancy:

pCO2 in blood

Answer 13

decreases

Question 14

Changes in Pregnancy:

TV

Answer 14

increases

*wtf is TV

Question 15

Changes in Pregnancy:

MV

Answer 15

increases

*wtf is MV

Question 16

Changes in Pregnancy:

Immune response

Answer 16

decreases

*pregnant women are more susceptible to infections

Question 17

Both ___ and ___ increase, therefore CO increases tremendously

Answer 17

HR and SV

Question 18

____ decreases quite a bit over pregnancy

slide 13

Answer 18

albumin

Question 19

_____ decreases a little over pregnancy

slide 13

Answer 19

hematocrit

Question 20

see pic on slide 17

Answer 20

okay

Question 21

What are the placenta’s major functions?

Answer 21

• Transfer nutrients and oxygen from the mother to the fetus
• Assist in the removal of waste products from the fetus to the mother
• Synthesis of hormones, peptides and steroids
• Provides a link between the circulations of 2 distinct individuals
• Barrier to protect the fetus fro drugs/toxins in the maternal blood

Question 22

Fetal kidneys are immature which means ?

Answer 22

• filtration reduced

- increases with gestational age

Question 23

List some ADRs of drugs in pregnancy

Answer 23

• Teratogenesis (birth defects or malformations)
• Osteoporosis
• Uterine stimulation
• Uterine suppression
• Drug dependent infant
• Breathing difficulties in neonate
• Impaired intellectual or social development

Question 24

List some points about Teratology

Answer 24

• Manifests in offspring at time of delivery
• Attributable to maternal toxins during pregnancy
• Risk of malformation with most teratogens is about 10%
• Interest stimulated all over world following thalidomide tragedy in 1961

Question 25

Why is it hard to prove a drug is teratogenic?

Answer 25

- Incidence of congenital anomalies is low - Animal tests may not be applicable - Exposure often needs to be prolonged - Controlled experiment that cannot be done in humans - Neurodevelopmental and behavioural issues often hard to identify and/or link

Question 26

List the criteria to prove a drug is a teratogen

Answer 26

- Must cause specific set of malformations - Act only between 4-7 weeks of gestation - Incidence should increase with increasing dose and duration of exposure

Question 27

What are Shepard's Principles of Teratology?

Answer 27

- The agent must be present during the critical periods of development - Acts directly on the embryo - Experimental models corroborating the findings (i.e. biological plausibility) fetus or on the placenta

Question 28

Fetal effects from drugs depend on several factors: | What are they?

Answer 28

``` 1) Time: When drug is taken in pregnancy Preimplantation/presomite period: conception to 2 week Somite period: 2-4 weeks Organ/structure formation: 4-8 weeks Organ function/substructure: 8+ weeks ``` 2) Dose: High dose - may be lethal/death/abortions Low dose- may be nothing

Question 29

What kind of malformations happen in the embryonic period (3-8 weeks = first trimester)

Answer 29

gross malformations

Question 30

What kind of problems happen in the fetal period (9-40 weeks)

Answer 30

function problems rather than gross anatomy - learning deficits and/or behavioural abnormalities

Question 31

see slide 31-33

Answer 31

prob won't but ok sam

Question 32

What happened when Diethylstilbestrol (DES) was given to pregnant women?

Answer 32

- Given to prevent miscarriages in high risk pregnancies - Cases of vaginal cancer in women ages 16-20, linked to DES ingestion early in pregnancy - Female children born with vaginal and cervical carcinomas as well as uterine anomalies - Male offspring had abnormal genitalia/sperm defects

Question 33

What happened when Thalidomide was given to pregnant women?

Answer 33

- Thalidomide is an anti-emetic, sleeping pill prescribed mid-1950's, early 1960's as non toxic drug - Single treatment used during first trimester - capable of producing teratogenesis - Approximately 10,000 children affected with serious malformations

Question 34

What were some malformations caused by Thalidomide?

Answer 34

- Phocomelia (absence of limbs - hands and feet are attaches closely to the trunk) - Congenital heart defects - Eye defects - Urogenital defects - GI defects - Hearing loss

Question 35

How is depression in pregnancy treated?

Answer 35

- Affects up to 20% of pregnant women (SSRIs appear safe) - Women commonly discontinue therapy; high morbidity associated with DC therapy - Those treated are usually treated with very low average doses

Question 36

Are SSRIs safe in pregnancy?

Answer 36

- they APPEAR safe - after 15 years of reassuring data analysis, recent reports of excess cardiac malformations, mostly with paroxetine - studies are contradictory

Question 37

Describe the Perception of Teratogenic Risk

Answer 37

- Even when exposed to non-teratogenic drugs women assign 25% teratogenic risk - Evidence-based counselling can prevent unnecessary pregnancy terminations