Lecture 15 - Drugs in Pregnancy Flashcards
Changes in Pregnancy:
Creatinine clearance
increases
Changes in Pregnancy:
Drug metabolism
variable
Changes in Pregnancy:
Most protein binding
increases
*albumin binding decreases
Changes in Pregnancy:
gastric emptying
decreases
Changes in Pregnancy:
plasma volume
increases by 50%
Changes in Pregnancy:
Absorption from skin
increases (increased vascularity)
Changes in Pregnancy:
cardiac output
increases by a lot
Changes in Pregnancy:
peripheral resistance
decreases
Changes in Pregnancy:
diastolic BP
decreases
Changes in Pregnancy:
pulmonary resistance MV
increases
Changes in Pregnancy:
colloid oncotic pressure
decreases
Changes in Pregnancy:
pH in blood
increases
Changes in Pregnancy:
pCO2 in blood
decreases
Changes in Pregnancy:
TV
increases
*wtf is TV
Changes in Pregnancy:
MV
increases
*wtf is MV
Changes in Pregnancy:
Immune response
decreases
*pregnant women are more susceptible to infections
Both ___ and ___ increase, therefore CO increases tremendously
HR and SV
____ decreases quite a bit over pregnancy
slide 13
albumin
_____ decreases a little over pregnancy
slide 13
hematocrit
see pic on slide 17
okay
What are the placenta’s major functions?
- 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
Fetal kidneys are immature which means ?
- filtration reduced
- increases with gestational age
List some ADRs of drugs in pregnancy
- Teratogenesis (birth defects or malformations)
- Osteoporosis
- Uterine stimulation
- Uterine suppression
- Drug dependent infant
- Breathing difficulties in neonate
- Impaired intellectual or social development
List some points about Teratology
- 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
Why is it hard to prove a drug is teratogenic?
- 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
List the criteria to prove a drug is a teratogen
- Must cause specific set of malformations
- Act only between 4-7 weeks of gestation
- Incidence should increase with increasing dose and duration of exposure
What are Shepard’s Principles of Teratology?
- 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
Fetal effects from drugs depend on several factors:
What are they?
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
What kind of malformations happen in the embryonic period (3-8 weeks = first trimester)
gross malformations
What kind of problems happen in the fetal period (9-40 weeks)
function problems rather than gross anatomy - learning deficits and/or behavioural abnormalities
see slide 31-33
prob won’t but ok sam
What happened when Diethylstilbestrol (DES) was given to pregnant women?
- 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
What happened when Thalidomide was given to pregnant women?
- 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
What were some malformations caused by Thalidomide?
- Phocomelia (absence of limbs - hands and feet are attaches closely to the trunk)
- Congenital heart defects
- Eye defects
- Urogenital defects
- GI defects
- Hearing loss
How is depression in pregnancy treated?
- 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
Are SSRIs safe in pregnancy?
- they APPEAR safe
- after 15 years of reassuring data analysis, recent reports of excess cardiac malformations, mostly with paroxetine
- studies are contradictory
Describe the Perception of Teratogenic Risk
- Even when exposed to non-teratogenic drugs women assign 25% teratogenic risk
- Evidence-based counselling can prevent unnecessary pregnancy terminations
