Population Specific Pharmacotherapy Flashcards
Two membranes of the placental barrier
ST (syncytiotrophoblastic layer)
CT (cytotrophoblastic layer)
Which placental barrier layer is outside?
ST
Which placental barrier layer is on the inside?
CT
What is the purpose of the placental barrier?
to serve as a barrier preventing drug transport across the placenta
What are 3 characteristics that make a substance cross the placental barrier easier?
low molecular weight, un ionized, higher lipophilicity
in terms of placental permeability, lipid permeability is directly proportional to ______ and permeability is inversely proportional to _______
lipophilicity; molecular size
medications sized <500 Da
cross placental barrier easily
medications sized 500-1000 Da
cross with difficulty
medications sized >1000 Da
cross very poorly
Medications with high lipophilicity and low molecular weight will
cross the placenta easily
Protein bound drugs and placenta
Free form may cross but anything bound to protein would have difficulty
Drug movement across the placental membrane is reduced by
efflux transporters
What are the transporters that exist on the membrane of the placenta? (4)
P-glycoprotein
BCRP
MRP1
MRP2
In what layer of the placental barrier are phase I and phase II enzymes located?
ST
the amount of enzymes in the placental barrier are much ___ than in the liver
less
amount of enzymes in the placental barrier change with _____
gestational age
Metabolism of meds that pass through the placental barrier
small amount of metabolism takes place. if they do pass through and are not effluxed out, they can pose potential harm to the fetus.
4 different types of drugs that reach the fetus
- drugs which have favorable effects on the fetus
- drugs which have no effect on the fetus
- drugs that have adverse effects on the fetus
- teratogens which are drugs that effect embryonic of fetal development.
Always check ____ when prescribing meds to pregnant women
teratogenicity
If toxicities occur in the placenta between weeks 3 and 8, what can you expect?
abnormalities in development of the fetus
What needs to be considered if a mother really requires a medication during fetal development?
how severe is the potential effect? is it temporary or permanent?
teratogens
medications that will cause malformation of an embryo
Teratogenic effects most often occur during
organogenesis
Expression of teratogenic effects depend on
drug
fetal variability
Phenytoin as a teratogen (and its effects)
It is a highly protein bound drug. The protein bound phenytoin will not cross the placenta but all of the free phenytoin can cause harm such as growth retardation, microcephaly, mental retardation, and a broad depressed nasal bridge
Lithium as a teratogen
causes cardiac malformation
Methotrexate as a teratogen
will cause skeletal malformation
tetracycline as a teratogen
stained teeth and hypoplasia of enamel
alcohol as a teratogen
intrauterine growth retardation, mental retardation, microcephaly, and joint abnormalities
Teratogenic risk category A
Possibility of fetal harm appears remote
FDA teratogenic risk category A and B
okay to administer
Teratogenic risk category B
Either animal reproduction studies have not demonstrated fetal risk
or
controlled studies did not demonstrate adverse effects and there is no evidence of risk in later trimesters
FDA teratogenic risk C
Should only be given is benefit > risk
Teratogenic risk D
Pharmacy will typically intervene
Teratogenic risk category X
risk clearly outweighs any possible benefit
Women who are pregnant or planning to become pregnant and are on ACE inhibitors
will likely be changed to labetolol or methyldopa
Unbound medications and lactation
Unbound form will easily pass from plasma to milk, and can pass back.
Because babies (assuming they are breast fed) do not metabolize drugs at an adult level,
we need to know if drugs passing into breastmilk will harm the baby
5 factors that promote drug transfer into milk
small volume of distribution low protein binding high lipophilicity un ionized low molecular weight
Highly protein bound medications can still effect fetus/breast milk because
the free form may still be able to circulate, and even small concentrations can have a profound effect on a neonate.
Chloramphenicol causes what in babies
Gray Baby Syndrome.
Mechanism of Gray Baby Syndrome
Immature liver enzyme, UDP-glucuronosyltransferase, results in an accumulation of toxic metabolites. Can be fatal.
Symptoms of gray baby syndrome (6)
cyanosis ash gray color of skin lethargic eyes limp body tone hypotension death
Benzyl alcohol causes what in babies?
Gasping syndrome
Symptoms of gasping syndrome (4)
gasping respirations
severe metabolic acidosis
hypotension
death
mechanism of gasping syndrome
immature ability to conjugate benzoic acid with glycine, resulting in an accumulation of benzoic acid.
total body water % in adults vs neonates and its implications
adults: 65%
neonates: 80%
more water and less albumin means less protein for protein bound drugs to bind to.
Acid secretion in adults vs neonates and its implications
Neonates have much less gastric acid secretion. There will be less breakdown in the stomach and more drug available in circulation, necessitating lowest doses of medications.
At what age is adult renal function achieved?
age 2
GFR in neonates as compared to adults and its implications
Neonatal GFR is much lower than adult level, necessitating lower doses because medications will not be cleared as quickly.
Integumentary differences in neonates and adults
neonates have much thinner stratum corneum and an increased perfusion to cutaneous tissue. This implies an increased absorption of topical medications. Neonates have a higher body surface:weight ratio.
