Pharmacology in Special Populations - Pregnancy Flashcards
What are different maternal physiologic characteristics to keep in mind when prescribing medications to pregnant women?
- cardiovascular function
- respiratory function
- renal function
- GI function
What type of cardiac output (increased/decreases) do moms have during pregnancy and how does this affect blood volume?
mom’s have increased cardiac output, leading to increased blood volume by 40-50%
How is albumin affected in pregnant women? What can this cause?
- albumin is decreased
- causes edema
What happens to the upper airway mucosa in pregnant women?
there is increased edema and hypervascularity
What is the volume remaining in the lungs after a normal, passive exhalation?
residual capacity
How is functional residual capacity of the lungs affected in pregnant women?
it is decreased
What is more likely to happen in surgery with pregnant women due to there being a decrease in residual capacity of the lungs?
hypoxemia
How is renal blood flow affected in pregnant women? How does this affect GFR?
- renal blood flow is increased
- this leads to an increased GFR
Because pregnant women have an increased renal blood flow and increased GFR, how would this affect drug elimination?
drugs would be filtered through and removed from the body at a quicker rate than expected, so the time the drug is working may be shorter than expected
How is total body water affected in pregnant women (what are the numbers)?
total body water is increased
- 6L extracellular
- 2L intracellular
How is gastric emptying time affected in pregnant women? What does this mean?
- gastric emptying time is increased
- drugs/substances may take longer to empty from the stomach
How is bowel transit time affect in pregnant women? What about bowel motility?
- bowel transit time is increased
- motility is decreased
Having an increased bowel transit time means what for pregnant women?
substances may take longer to get through the bowel
What are different pharmacokinetic concepts you have to consider in pregnant women?
- half-life
- protein binding
- absorption
- volume of distribution
- metabolism
Drugs cleared renally in pregnant women will have what type of half-life?
a shorter half-life
How does clearance affect half-life?
- increased clearance, shorter half-life (pregnant women)
- decreased clearance, longer half-life
In pregnant women, drugs that are highly protein bound may have (1)
- higher free levels
Because women have decreased albumin, free drug concentration will be (1) for drugs that are (2) protein bound
- increased
- highly
What can happen in pregnant women due to highly protein bound drugs possibly having higher free drug concentration?
there can be an increase in pharmacological (drug) effects
How is absorption of drug affected in pregnant women due to slow gastric emptying and GI motility delays?
absorption may be increased
- can be decreased; depends on specific drug and where in the GI tract it sits the longest
What can be altered (think about graphs) in absorption of drug in pregnant women?
Cmax and Tmax
What is Cmax?
concentration of drug to reach peak effect
What it Tmax?
time it takes for drug to reach maximum concentration
If a drug is sitting somewhere where it is readily absorbed, how will Cmax be affected?
Cmax will be higher
What may prohibit dose absorption completely in pregnant women (can happen to anyone)?
vomiting
Where is the best place to see how much of a drug was absorbed?
area under the curve
How do you find area under the curve (F-bioavailability)?
concentration following oral dose/concentration following IV dose
How is volume of distribution affected in pregnant women?
volume of distribution is increased
In pregnant women, there is an increase in (1) and (2) which leads to a loss of (3) from plasma into other (4)
- extracellular (and)
- intracellular water
- hydrophilic drugs
- water rich spaces
Hydrophilic drugs want to move where?
where water in going
In pregnant women, there is an increase in body fat, which increases (1) for (2)
- volume of distribution (for)
- lipophilic drugs
Lipophilic drugs want to move where?
where there is fat
What cytochromes are increased in phase I metabolism in pregnant women?
- CYP3A4
- CYP2D6
- CYP2C9
Increases in cytochrome activity will lead to what?
drugs being metabolized at an increased rate - going through the body much faster; may have decreased effect of drug
What cytochromes are decreased in phase I metabolism in pregnant women?
- CYP1A2
- CYP2C19
Decreases in cytochrome activity will lead to what?
drugs being metabolized at a decreased rate - instead of getting out of system, may build up and lead to toxic effects (drug will have increased activity)
What is responsible for glucuronidation of many drugs?
UGT1A4
UGT1A4 in involved in what phase of metabolism?
phase II
In phase II metabolism in pregnant women, how is UGT1A4 activity affected?
UGT1A4 activity is increased
How does UGT1A4 activity being increased affect drugs in the body of pregnant women?
would clear drugs faster; may have decreased drug effect
Changes in metabolism will effect (1)
- half-lives
What are important drug characteristics that determine the ability to cross the placental barrier in pregnant women?
- lipid solubility
- molecular size
- pH and ionization
- placental transporters
- protein binding
- metabolism
How can lipid solubility affect drug’s ability to cross the placental barrier?
if it’s more lipid soluble, it will be more likely to cross placental barrier
How can molecular size affect drug’s ability to cross the placental barrier in pregnant women?
larger molecules won’t cross the placental barrier
How can pH and ionization affect drug’s ability to cross the placental barrier in pregnant women?
if maternal blood is more basic than fetal blood, drugs can become trapped, which can cause toxicity
How can placental transporters affect drug’s ability to cross the placental barrier in pregnant women?
transporters pump stuff out of cells away from fetus back into maternal circulation
How can protein binding affect drug’s ability to cross the placental barrier in pregnant women?
it can make it harder to cross the placental barrier
How can metabolism affect drug’s ability to cross the placental barrier in pregnant women?
some drugs can be metabolized in the placenta and be deactivated
- if baby has function liver, they may be able to metabolize drug but may cause toxicity if it can’t be metabolized and become trapped
What are some different pharmacodynamic concepts you need to consider with pregnant women?
- maternal physiology
- fetal therapeutics
- fetal toxicity
- teratogenicity
Pregnant women have a(n) (1) sensivity to some drugs such as inhaled and Iv anesthetics?
- increased
Pregnant women may have (1) due to physiologic changes and may require new drug therapies
- development of new problems
What are some issues pregnant women may develop during their pregnancies?
- heart failure
- diabetes
In pregnant women with newly developed heart failure, circulation is (1) so there is (2) drug movement
- lower
- not enough (drug movement)
What describes when medication is administered to pregnant women with the fetus as the target?
fetal therapeutics
In fetal therapeutics, what can be given to the mother for lung development of the fetus if preterm birth is anticipated?
corticosteroids
In fetal therapeutics, what can be given to the mother to treat fetal arrhythmias?
antiarrhythmics
In fetal therapeutics, what can be given to the mother to decrease HIV transmission to the fetus?
antivirals
What is often predictable based on what we know about drugs; but can sometimes not be predictable with new medications?
fetal toxicity
In (1), the mechanisms are poorly understood and have many components
- teratogenicity
What demonstrates characteristic malformations or may cause termination of the pregnancy?
teratogens
What describes a substance that demonstrates characteristic malformations that occur at a specific stage of development?
teratogen
What describes when a substance is dose-dependent for malformations to occur?
teratogenicity
What includes physical malformations, neurocognitive deficits, growth restriction, spontaneous abortion, and stillbirth?
teratogenicity
Teratogenic risk is about (1)%
3%
Periods of (1) and (2) are most subject to teratogenic effects of a substance
- rapid growth
- cell differentiation
What is of little benefit due to differences in fetal development when regarding teratogenicity?
animal testing
Prenatal death from a teratogen may occur when during pregnancy?
the first 1-2 weeks
Major morphologic abnormalities from a teratogen may occur when during pregnancy?
3-7 weeks
Physiologic defects and minor morphologic abnormalities from a teratogen may occur when during pregnancy?
8 weeks to full term
What is a common teratogen used for sedative effects and, later, to suppress morning sickness in pregnant women?
thalidomide
What is thalidomide currently used for?
treatment of leprosy and cancer
What has been shown to lead to improper blood vessel growth, short limbs, missing limbs, organ malformations, blindness, deafness, external and internal ear structure malformations?
thalidomide
What is a common teratogen that can lead to:
- small eye openings
- thin upper lip
- smooth, wide philtrum
- small head circumference
- underdeveloped jaw
alcohol (fetal alcohol syndrome)
What is a common teratogen that deposits in bone and teeth affecting bone growth and causing tooth discolor/defects?
tetracycline
What is a common teratogen that impairs fetal renal development and causes cranial malformations?
ACE inhibitors/ARBs
What is a common teratogen that can be used to treat seizures and is associated with neural tube defects and can cause:
- anencephaly
- spina bifida
- encephalocele
- iniencephaly
valproic acid
What is a common teratogen that can cause:
- cleft palate
- undersized jaw
- heart defects
- ear defects?
isotretinoin (accutane)
What is a common teratogen that causes:
- hypoplastic nasal bridge
- heart defects
- cartilage defects
- risk of bleeding
warfarin
What is a common teratogen that causes:
- growth restriction
- premature delivery
- SIDS
- neurocognitive delays
nicotine
What is a common teratogen used for treatment of seizures and migraines and causes cleft palate?
topiramate
What is a common teratogen that causes:
- ebstein anomaly (tricuspid valve anomaly)
- various cardiac abnormalities
- neonatal toxicity
lithium
What can cause fetal hydantoin syndrome?
phenytoin (epilepsy medication)
What is a common teratogen that causes:
- abnormal dermatoglyphics
- outer ear abnormalities
- depressed nasal ridge, short nose
- intrauterine growth restriction
- microcephaly
- midfacial hypoplasia
- hypoplastic nails and phalanges
- neurological deficits
phenytoin
