Drug therapy and breastfeeding
Which characteristic of a drug allows it to enter the central nervous system as well as to enter breastmilk? A) High lipid solubility B) Low protein binding capacity C) High molecular weight D) Half-life greater than 8 hours
(A) The most important feature of lipid solubility is that the more lipid soluble the medication, the more likely it will transfer into human milk. A more practical feature of this relationship is that most central nervous system (CNS)-active drugs are both low in molecular weight and very lipid soluble—two kinetic parameters that permit them to transfer through the blood-brain barrier as well as into human milk. Hence, greater concern for the infant should be taken with CNS-active drugs.
A maternal medication with which of the following characteristics will pass most readily into breastmilk? A) High lipid solubility, low molecular weight B) Low lipid solubility, low molecular weight C) Not protein bound, high molecular weight D) Protein bound, moderately lipid soluble
(A) A medication such as lithium, which has no protein binding and low molecular weight, transfers into milk readily. Many of the psychotropic drugs, such as the amphetamines, have low molecular weights and are highly lipid soluble, which accounts for their rapid entry into the central nervous system as well as their higher milk/plasma ratios in human milk.
Therapeutic dosages of penicillins and cephalosporins in breastfeeding mothers have been measured in her breastmilk in: A) Trace concentration only B) Amounts of about 5% of the mother's dose C) Concentrations that vary inversely with the number of days that the mother takes the medication D) Concentrations typically too low to cause changes in the baby's intestinal flora
(A) Aside from analgesics, the most commonly used class of medications in breastfeeding mothers is the antibiotics. Virtually all the penicillins and cephalosporins have been studied and are known to produce only trace levels in milk; however, some changes in intestinal flora are to be expected.
Contraceptives that contain estrogen or progestogen: A) Are more likely to reduce breastmilk volume if begun in the first month postpartum B) Are best begun in the immediate postpartum to help ameliorate hormonal swings C) Have not been found to reduce breastmilk volume regardless of when they are introduced D) May increase breastmilk volume if delayed until at least 4 months postpartum
(A) Due to the conflicting data, when hormonal contraception is necessary, low-dose progesterone-only oral contraceptives should be used or, if combined oral contraceptives are required, a product with a low estrogen level should be recommended. The most sensitive time for suppression is in the early postpartum period, before the mother's milk supply is established; therefore, waiting as long as possible (minimum 4 weeks) prior to use is advised (Queenan, 2012). All mothers who take hormonal contraception should be forewarned of possible effects on milk production and should be counseled to observe any changes in breastfeeding
During the first 2 days or so after childbirth, when lactocytes in the breast are _______ and intercellular spaces are _______, proteins pass from maternal plasma into colostrum _______. A) small / large / easily B) large / small / only with great difficulty C) large / small / easily D) small / large / only with difficulty
(A) During the early stages of lactation (colostral phase), when the lactocytes are small in size and the intercellular spaces are large, maternal substances, including drugs, lymphocytes, immunoglobulins, proteins, and other plasma substances, can easily transfer into human milk via these large intercellular gaps. Over time, with the drop in progestins, the lactocytes grow in size and subsequently narrow the intercellular gaps, eventually closing most of them.
A drug described as having a high milk: plasma ratio is usually ___________ for a fully breastfed infant if _________. A) Safe / the maternal plasma concentration is low. B) Safe / the infant ingests a large enough volume of breastmilk to dilute the drug. C) Unsafe / it has a short half-life. D) Unsafe / the infant is less than 6 weeks old.
(A) Most important, the M/P ratio is of limited clinical use in assessing the likelihood that a clinically relevant dose will be transferred to the infant during breastfeeding. Even with some drugs that have high M/P ratios (e.g., ranitidine), the absolute dose transferred to the infant is still subclinical. Ultimately, it is the concentration of drug in the milk (relative infant dose) and the volume of milk ingested that determine the clinical dose transferred to the infant. For this reason, low M/P ratios suggest that very little drug enters the milk. Conversely, high M/P ratios may or may not indicate high levels in milk because the key factor is the maternal plasma level of medication. The ratio of the concentration of drug in the milk to that in the plasma is known as the milk/plasma ratio (M/P). The M/P ratio is quite useful in determining the relative transfer of medication into milk, but there are significant difficulties in accurately measuring it. Because of differences in the rate of drug transfer, changes in plasma and milk concentrations of medications do not always follow one another, and the time at which the samples are drawn becomes incredibly important. For example, the M/P ratio may be 1.14 at zero time and 0.31 at 3 hours following administration.
In the case of a breastfeeding mother and infant, the "bioavailability" of a medication given to the mother generally refers to the: A) Proportion that reaches the mother's circulatory system B) Potential severity of the medication's effect on the infant C) Small but measureable nutritive content of most medications D) Proportion that reaches the intended site of action in the mother
(A) The bioavailability of a medication generally refers to the amount of drug that reaches the systemic circulation after administration. Depending on the route of administration (oral, intravenous [IV], intramuscular [IM], subcutaneous [SC], topical), medications may ultimately pass into the systemic circulation prior to reaching their intended site of action or the milk compartment.
The transfer of most drugs into human milk is facilitated by: A) Passive diffusion down a concentration gradient B) Active transport by another agent C) Impermeable alveolar membranes D) Ionized or bound compounds
(A) The transfer of drugs into human milk is usually facilitated by passive diffusion down a concentration gradient formed by the non-ionized, free drug on each side of the semipermeable membrane. Normally, drugs transfer from areas of high concentration to areas of low concentration (passive diffusion). As described earlier, the overall rate and degree of transfer may be initially affected by the stage of alveolar development and the junctional condition of the lactocytes.
To minimize the amount of a particularly toxic maternal drug ingested by a breastfeeding infant, a mother can: A) Feed milk that was stored before she began taking the medication B) Express milk during the course of medication and save it for later use, when the drug has decayed C) Prefer medications with low molecular weight or low protein-binding capacity D) Use a medication with a relatively long half-life
(A)Avoid feeding the infant or pump and discard the mother's milk at Cmax. Because milk levels are invariably a function of maternal plasma levels, avoiding breastfeeding at the peak concentration (Cmax) will always reduce infant exposure to higher drug levels in milk. While useful for shorter half-life medications, this advice is of questionable use with medications having a long half-life, and its feasibility in real life is questionable. Temporarily withhold breastfeeding for brief exposures. If the mother can store sufficient milk for a brief exposure to medication (e.g., radiocontrast test), then the risk to the infant is eliminated. Milk produced during the exposure can be pumped and discarded. Choose medications that have minimal levels in milk, and when possible, choose the medication in a class of drugs with the smallest relative infant dose. However, all medications should be evaluated for their efficacy in the specific syndrome. Sometimes, there are no better alternatives.
Maternal medications can: A) Be cleared from breastmilk only by pumping the breasts for twice the half-life of the last dose B) Diffuse from breastmilk back into plasma as plasma concentration falls C) Be trapped in breastmilk because the alveolar membrane is easily porous only in the "inbound" direction D) Move from breastmilk back into plasma only before tight junctions form between alveolar cells
(B) Drugs enter and exit the milk compartment largely as a function of their physiochemistry. The retrograde diffusion of drugs from the milk back into the plasma is well documented and is probably controlled by the same kinetic factors as those that influence drugs' entry into breastmilk. As the maternal plasma level of medication increases, so does the transfer into milk. Then, as the mother metabolizes or eliminates the medication and her plasma levels begin to drop, most drugs diffuse out of the milk compartment and back into the maternal plasma compartment to be eliminated by the mother
Maternal medications can: A) Be cleared from breastmilk only by pumping the breasts for twice the half-life of the last dose B) Diffuse from breastmilk back into plasma as plasma concentration falls C) Be trapped in breastmilk because the alveolar membrane is easily porous only in the "inbound" direction D) Move from breastmilk back into plasma only before tight junctions form between alveolar cells
(B) Drugs enter and exit the milk compartment largely as a function of their physiochemistry. The retrograde diffusion of drugs from the milk back into the plasma is well documented and is probably controlled by the same kinetic factors as those that influence drugs' entry into breastmilk. As the maternal plasma level of medication increases, so does the transfer into milk. Then, as the mother metabolizes or eliminates the medication and her plasma levels begin to drop, most drugs diffuse out of the milk compartment and back into the maternal plasma compartment to be eliminated by the mother.
As compared with the mother's dose, the "relative infant dose" of a breastfeeding mother's medication refers to the concentration of the drug that: A) Survives transit through the infant's stomach B) Is in breastmilk C) Is transported into the infant's bloodstream D) Is ultimately absorbed by the infant
(B) Many clinicians use a 150 cc/kg/day value to estimate the amount of milk ingested by the infant. The following formula estimates the clinical dose to the infant: Dinf equals Drug concentration in milk (at Cmax or Cav) multiplied by volume of milk ingested. However, the most useful and accurate measure of exposure is to calculate the relative infant dose (RID): Relative infant dose equals Dinf (mg/kg/day) / Maternal dose (mg/kg/day). This value, which is generally expressed as a percentage of the mother's dose, provides a standardized method of relating the infant's dose to the maternal dose. In full-term infants, Bennett (1996) recommends that a relative infant dose of more than 10% should be the theoretical "level of concern" for most medications. Nevertheless, the 10% level of concern is relative, and each situation should be individually evaluated according to the overall toxicity of the medication. Ultimately, it is the concentration of drug in the milk (relative infant dose) and the volume of milk ingested that determine the clinical dose transferred to the infant.
The proximal capillaries serve as the primary source of: A) Bile, which will help with the digestion of fats B) Immunoglobulins C) Estrogen D) Oxytocin
(B) The alveolar unit is lined with specialized epithelial cells called lactocytes. The entire alveolar unit is thoroughly perfused with capillaries and lymphatics and is innervated with small nerves. Closely juxtapositioned to the basal membrane of the alveolus are numerous capillaries that serve as the primary source of immunoglobulins, fats, and many other components (including drugs) needed for the production of human milk.
The safety of a maternal drug for a breastfeeding infant typically depends on: A) Ease of clearance by the mother but not the infant B) Inherent toxicity C) Likelihood of being protein bound D) Bioavailability in just the mother
(B) Ultimately, the evaluation of the safety of drugs in breastmilk depends on at least four major factors: the amount of medication present in milk, the oral bioavailability of the medication, the inherent toxicity of the drug, and the ability of the infant to clear the medication. While we know milk levels for many hundreds of drugs and their approximate bioavailability, the ability of the infant to clear the medication is highly variable and still requires individual valuation by the clinician.
Which statement below about the use of a radiolabeled compound by a breastfeeding mother is true? A) Is facilitated by the long half-life of most of those compounds B) Is almost always contraindicated until she has weaned her infant C) Is most hazardous for iodine-131, which concentrates in breastmilk D) Thallium-201 only requires a brief interruption of breastfeeding and discarding of pumped milk
(C) Commonly used as diagnostic tools, the majority of these radioactive compounds have rather brief half-lives and do not pose a major problem for breastfeeding mothers. They can simply pump and discard their milk for 12-24 hours and continue to breastfeed. However, with the use of iodine-131, gallium-67, or thallium-201, longer pumping periods may be necessary and may preclude breastfeeding altogether. The most dangerous radioisotope is iodine-131. It is concentrated in human milk (approximately 16- to 23-fold), may potentially destroy the infant's thyroid, and could ultimately increase the risk of thyroid carcinoma in the infant exposed to this isotope via milk. The Nuclear Regulatory Commission (NRC) recommends discontinuing breastfeeding altogether. Because the level of radioactive iodine in breast tissue is so high, women who require high doses of I-131 should probably discontinue breastfeeding for several weeks prior to use to avoid high radiation doses to their breast tissues.
Which of the following characteristics of a drug promotes its transfer into human milk? A) Greater tendency to bind to proteins B) Lesser tendency to dissolve in fats C) Lower molecular weight D) Low concentration in maternal plasma
(C) Drugs transfer into human milk largely as a function of their physicochemical characteristics, which include their molecular weight, lipid solubility, protein binding, and pKa. The smaller the molecular weight of the medication (300 daltons or less), the greater the rate of diffusion across the bilayer lipid membranes. 5-15% triglycerides are found in human milk. As such, some medications that are lipid soluble may immerse themselves in the lipid fraction of milk and transfer to the infant.
A medication given to a breastfeeding mother is least likely to enter her systemic circulatory system if it was administered: A) Orally B) Intravenously C) Topically D) Intramuscularly
(C) Fortunately, many medications are unstable in the gastric milieu or are incompletely absorbed by infants. Most, but not all, topical medications are poorly absorbed transcutaneously, so they seldom attain significant plasma levels. When drugs are administered orally, the liver sequesters or metabolizes many medications, preventing their entry into the plasma compartment. Thus the poor bioavailability of many products reduces the exposure level in breastfed infants.
To increase the milk supply of mothers of premature infants, a dopamine antagonist such as metoclopramide: A) Acts by inhibiting dopamine release from the posterior pituitary B) Can help mothers who have a low plasma oxytocin concentration C) Can help mothers who have a low plasma prolactin concentration D) Promotes the secretion of prolactin in the hypothalamus
(C) In some mothers, particularly those with premature infants, prolactin levels may not be sufficient to support adequate lactation. In these patients, medications that inhibit dopamine receptors in the hypothalamus (e.g., metoclopramide, domperidone) may or may not stimulate milk production. Prolactin release from the pituitary is inhibited by dopamine from the hypothalamus. Consequently, any drug that inhibits dopamine will ultimately increase prolactin release.
Low concentrations of a drug in mother's milk may be promoted by: A) long half-life of the drug B) Generalized diffusion across semipermeable blood vessel walls C) Poor absorption of the drug D) The drug's slow uptake from plasma by other organs
(C) It is important to understand that if a drug is not absorbed in the mother or is rapidly depleted from her plasma compartment to other compartments (rapid redistribution), the transfer to her milk compartment will be quite low. Drugs with brief half-lives will be eliminated so quickly that they seldom pose a major risk to the infant.
With respect to the transfer of medications, which of the following statements is true? Most medications: A) Are contraindicated in the breastfeeding mother B) If taken by mouth, are destroyed in the mother's stomach C) Produce low, subclinical concentrations in human milk D) Pass into human milk in concentrations of clinical concern
(C) It is true that all medications transfer into human milk. However, the vast majority do so in levels that are incredibly low, are almost always subclinical, and pose no real risk for most infants. Nevertheless, all infants should be evaluated for risk prior to their mothers taking medications, and those infants deemed at high risk should be exposed to only medications that carry a minimal risk associated with their use. In reality, we do have a rather extensive database on drugs and their transfer into human milk.
A mother who uses the drug metoclopramide to stimulate milk production may experience: A) Decreased milk production B) Transfer of moderately large concentrations of metaclopramide into her milk C) A dose-related effect of metoclopramide on prolactin stimulation D) A sharply increase milk supply following rapid withdrawal of the drug
(C) Metoclopramide is the most commonly used agent and, in some cases, profoundly stimulates milk production as much as 100%. Unfortunately, it may induce significant depression if therapy is continued for more than a month. The prolactin-stimulating effect of metoclopramide is dose related, with doses of 10-15 mg three times daily required for efficacy. The amount transferred into milk is small, ranging from 28 to 157 µg/L in the early puerperium, which is far less than the clinical dose administered directly to infants (800 µg/kg/day) (Kauppila et al., 1981). The most significant side effects of metoclopramide are extrapyramidal symptoms, gastric cramping, and (in some cases) major depression. Because a mother's milk supply is dependent on an "elevated" prolactin level, the precipitous withdrawal of these agents may result in a significant loss of milk supply. A slow withdrawal is generally recommended over several weeks to a month to prevent loss of milk supply.
During postpartum days 3 through 5, which of the following takes place? A) Spaces between lactocytes increase B) Transfer of maternal proteins into the breast fluid increases C) Transfer of maternal medications into the milk diminishes D) Total number of lactocytes increases rapidly
(C) Over time, with the drop in progestins, the lactocytes grow in size and subsequently narrow the intercellular gaps, eventually closing most of them. As can be seen from the transition from colostrum to mature milk, changes in breastmilk occur because of rapid growth of the lactocytes, ending in closure of the tight junctions between the cells. At 36 hours following delivery, a major change in the components of milk occurs, which is complete by 5 days postpartum. With closure of the intercellular spaces, the transfer of maternal medications and other maternal proteins into the mother's milk is greatly reduced.
Marijuana smoked in large amounts by a breastfeeding mother: A) Accumulates to relatively high concentrations in maternal plasma B) Is stored briefly—only a few days—in maternal adipose tissue C) Seems to produce only low concentrations in breastmilk D) Produces lethargy in her breastfed infant
(C) The effect of marijuana in breastfeeding mothers is rather unclear. To date, neurobehavioral effects on infants have not been reported, even in heavy smokers (Perez-Reyes & Wall, 1982). Marijuana passes rapidly out of the plasma compartment and enters adipose tissue (stored for weeks to months). Because of this rapid redistribution, milk levels are apparently low.
Which of the following is true of the pituitary hormone prolactin? A) Higher levels always increase milk production B) Is only slightly elevated, about 200 nanograms per milliliter at 6 months postpartum C) May be related to poor milk synthesis once they fall to 20 milligrams/deciliter or less D) Is directly related to volumes of milk produced during the course of lactation
(C) The pituitary hormone prolactin is one of the major controllers of milk production. It is well known that while prolactin levels must be elevated for milk production to occur, higher levels of prolactin do not necessarily increase production. In essence, you have to have enough prolactin to maintain milk synthesis, but overwhelmingly high levels do not make more milk. Thus, prolactin levels and milk production are not necessarily related. Initially, prenatal prolactin levels are quite high (200 ng/mL or higher) but then drop significantly over the next 6 months, to slightly elevated levels in the 70 ng/mL range. Mothers whose prolactin levels fall to the nonpregnant, nonlactating range of less than 20 ng/mL may suffer from poor milk synthesis.
Regular marijuana smoking by a breastfeeding mother: A) Accumulates in the breastmilk in higher concentrations compared to maternal plasma B) Is stored briefly—only a few days—in maternal adipose tissue C) Seems to produce only low concentrations in breastmilk D) Produces lethargy in her breastfed infant
(C) There is increasing concern regarding use of marijuana and other cannabis products in lactation. Limited human and animal studies suggest that early exposure is not benign and may cause long-term effects on motor development, behavior, and mental health. Marijuana is known to enter breast milk;, one case report of a woman smoking regularly (7 times per day) for more than 6 months revealed an eightfold accumulation of this drug in breastmilk compared with plasma (Perez-Reyes & Wall, 1982). Studies have shown significant absorption and metabolism in infants, although long-term sequelae are conflicting. In one study of 27 women who smoked marijuana routinely during breastfeeding, no differences were noted in growth or in, mental, and motor development (Tennes et al., 1985). In addition, no neurobehavioral effects were reported in the infants of two women who reported daily use (Perez-Reyes & Wall, 1982).
Maternal drugs that have a higher concentration in breastmilk than in plasma are: A) Limited to drugs that have a pH well below 7 B) Typically high-molecular-weight drugs C) Usually evidence of an active-transport mechanism D) Quite common
(C) Transport systems for medications may be indicated by drugs that have high milk/plasma ratios, although many drugs are ion trapped in milk due to the lower pH of milk and the higher pKa of the medication. Regardless, in the case of higher milk/plasma ratios, it is apparent that either the drug is ion trapped in the milk, or it is pumped into milk at higher levels (e.g., iodides).
The "clinical dose" of a medication that an infant receives through breastmilk depends principally on the concentration of the drug in the milk and: A) Whether the infant receives complementary foods, which may absorb some of the medication B) Whether the drug is excreted in the infant's urine (less effective) or feces (more effective) C) The volume of milk consumed by the infant D) The half-life of the drug in the infant's system
(C) Ultimately, it is the concentration of drug in the milk (relative infant dose) and the volume of milk ingested that determine the clinical dose transferred to the infant.
Which of the following characteristics of a drug promotes its transfer into human milk? A) Greater tendency to bind to proteins B) Lesser tendency to dissolve in fats C) Lower molecular weight D) Low concentration in maternal plasma
(C)Drugs transfer into human milk largely as a function of their physicochemical characteristics, which include their molecular weight, lipid solubility, protein binding, and pKa. The smaller the molecular weight of the medication (300 daltons or less), the greater the rate of diffusion across the bilayer lipid membranes. 5-15% triglycerides are found in human milk. As such, some medications that are lipid soluble may immerse themselves in the lipid fraction of milk and transfer to the infant
Breastfeeding infants are likely to be considered at high risk, with respect to a maternal medication, if they are: A) Delivered by C-section B) Full term but less than 30 days old C) Not stooling well D) Physiologically unstable
(D) A good clinical exam of the infant is mandatory to evaluate the relative risk of the medication to the infant. All infants should be categorized as low, moderate, or high risk for the medication of interest. Low-risk infants are generally older infants (6-18 months), who can metabolize and handle drugs relatively efficiently. Mothers in the terminal stage of lactation (more than 1 year after giving birth) often produce relatively smaller quantities of milk. Thus the absolute clinical dose transferred is often low to nil. Moderate-risk infants are those younger than 6 months who suffer from various metabolic problems, such as complications of delivery, apnea, GI anomalies, or other metabolic problems. High-risk infants include premature infants, newborns, unstable infants, and infants with poor renal output.
Compounds whose molecular weight exceeds ________ daltons are unlikely to pass into breastmilk. A) 300 B) 500 C) 800 D) 1000
(D) As the molecular weight of the medication exceeds 500-800 daltons, it becomes increasingly difficult to diffuse through the bilayer membranes and enter milk. Thus medications whose molecular weights exceed 1000 daltons seldom enter the milk compartment in clinically relevant amounts. Medications such as heparin, insulin, interferon, and other high-molecular-weight drugs simply do not pass into milk in clinically relevant amounts.
The greatest dosage of maternal medication will be transferred to a: A) 3-month-old infant who is taking close to 1 liter per day of mother's milk B) 1-month-old baby who is nursing 10 times in 24 hours C) 4-day-old neonate who is breastfeeding well but not yet stooling very often D) 36-week-old fetus linked by the placenta to her mother
(D) In this regard, it should always be remembered that many neonates may have been exposed in utero to drugs taken by their mothers and that in utero exposure may be an order of magnitude greater than that received via breastmilk. Thus infants exposed in utero to methadone go through significant withdrawal upon delivery, even when breastfeeding.
Of the strategies listed, which best reduces infant exposure to maternal medications? Medications that: A) Are generally considered safe for infants, and have a high relative infant dose B) Have minimal concentrations in plasma but penetrate the central nervous system well C) Have lower molecular weight and protein-binding capacity D) Have a known time-after-administration maximum concentration in breastmilk, so that the mother can pump and discard milk at that time
(D) Avoid feeding the infant or pump and discard the mother's milk at Cmax. Because milk levels are invariably a function of maternal plasma levels, avoiding breastfeeding at the peak concentration (Cmax) will always reduce infant exposure to higher drug levels in milk. Choose medications that are commonly used in pediatric patients and are considered safe. Choose medications with high protein binding (e.g., warfarin), because tissue and milk levels will be lower. Choose medications with poor penetration into the CNS, as they usually produce lower milk levels. Choose medications with higher molecular weights (e.g., heparin), as this factor greatly reduces transfer into milk
When a breastfeeding mother needs to use a medication, she should prefer a drug that has which characteristic? A) longer half-life, because maximum plasma concentration will be lower B) Greater bioavailability, so that it will be more effective and thus require fewer doses C) A relative infant dose of at least 12% D) That does not enter the central nervous system, because it is less likely to enter breastmilk also
(D) Avoid using medications when not absolutely necessary. This includes most herbal drugs. A relative infant dose of less than 10% is generally considered compatible with breastfeeding. Choose drugs with shorter half-lives over those with longer half-lives. Choose drugs with poorer bioavailability to reduce oral absorption in infants. Understand that drugs that enter the CNS will also likely enter breastmilk. An increased level of concern is recommended with such medications.
To minimize the dose of a maternal medication transmitted by breastmilk to an infant, use a medication that has a half-life that is ______ and is taken immediately ________a feeding. A) Long / after B) Long / before C) Short / before D) Short / after
(D) Following this reasoning, it is obvious that the diffusional forces that push medications into milk are highest at Cmax (peak) in the mother and lowest during the trough period when the mother is eliminating the medication. Thus, with drugs having a shorter half-life, one can avoid higher exposure to the medications by avoiding breastfeeding when the maternal plasma levels are highest, instead breastfeeding when the maternal levels are much lower. While this timing mechanism works to curtail transfer of some drugs, however, it will not work for medications with long half-lives, as the time period between Cmax and trough is prolonged in this case
To minimize the dose of a maternal medication transmitted by breastmilk to an infant, use a medication that has a half-life that is ______ and is taken immediately ________a feeding. A) Long / after B) Long / before C) Short / before D) Short / after
(D) Following this reasoning, it is obvious that the diffusional forces that push medications into milk are highest at Cmax (peak) in the mother and lowest during the trough period when the mother is eliminating the medication. Thus, with drugs having a shorter half-life, one can avoid higher exposure to the medications by avoiding breastfeeding when the maternal plasma levels are highest, instead breastfeeding when the maternal levels are much lower. While this timing mechanism works to curtail transfer of some drugs, however, it will not work for medications with long half-lives, as the time period between Cmax and trough is prolonged in this case.
Some medications are poorly absorbed into a mother's circulation because they are: A) Bound by IgG in the small intestine B) Applied subcutaneously C) Activated in the stomach D) Metabolized by the liver
(D) Fortunately, many medications are unstable in the gastric milieu or are incompletely absorbed by infants. Most, but not all, topical medications are poorly absorbed transcutaneously, so they seldom attain significant plasma levels. When drugs are administered orally, the liver sequesters or metabolizes many medications, preventing their entry into the plasma compartment. Thus the poor bioavailability of many products reduces the exposure level in breastfed infants.
As concentration of a drug peaks in maternal plasma, the drug's concentration in breastmilk typically is: A) High, especially if the drug is not well absorbed by the mother B) Low, because most of the drug is in maternal plasma C) Low, if the drug has a very long half-life D) Near its peak, because diffusion correlates the two
(D) In general, as the molar concentration of a drug in solution increases, the equilibrium gradient also increases to force the drug into other compartments. Thus, the more drug present, the higher the forces pushing it into the milk compartment. For this reason alone, the degree and rate of transfer of a drug into milk generally correlate with the plasma concentration curve. As the concentration in the plasma peaks (Cmax), it is quite common that milk levels peak as well. While this is certainly not always true, such as with metformin, the majority of drugs exhibit this feature.
The total dosage of a protein-bound drug transferred from a mother to her breastfeeding infant during the first 2 days postpartum is most likely to be_______, because_______. A) large / junctions between alveoli are open B) large / protein-bound drugs are more likely to appear in colostrum C) small / diffusion is not particularly efficient D) small / the volume of colostral fluid ingested on days 1 and 2 postpartum is small
(D) In the first 2-3 days of lactation, which are characterized by the production of small volumes of colostrum, the alveolar epithelial structure of the breast is quite open and porous. Thus many maternal proteins, lipids, immunoglobulins, and medications easily transfer into the milk compartment. Often drug levels in milk reach equilibrium with the plasma compartment (milk/plasma ratio ??1). As the lactocytes begin to swell after several days , the intercellular junctions close. This subsequently leads to dramatically lower levels of drugs in the milk compartment after the first week postpartum. While the transfer of medications or any substance into milk may be higher during the initial stages of early lactation, the absolute amount of colostrum delivered is often quite low (50-60 mL/day on days 1 and 2), so the clinical dose of medication delivered to the infant during this time is actually very low.
The rate of diffusion through alveolar cell membranes is _______ for compounds with a molecular weight _______ daltons. A) More rapid / greater than 800 B) Slower / of 300 to 800 C) Slower / less than 300 D) More rapid / less than 300
(D) With closure of the intercellular gaps, most medications that transfer into breastmilk enter via the "transcellular" pathway. To do so, they must enter the basal membrane of the lactocyte, diffuse gently through the cell, and exit via the luminal surface. The smaller the molecular weight of the medication (300 daltons or less), the greater the rate of diffusion across the bilayer lipid membranes
Which factor listed below helps to decrease the rate at which a drug is transferred from mother's plasma to breastmilk? A) Little binding to a protein B) High maternal plasma concentration C) High oral bioavailability of the drug in the mother D) High molecular weight
(D) Maternal factors that affect the rate of drug transfer include the relative oral absorption of the medication and the plasma levels of the medication. Of these many factors, the following are the most influential: maternal plasma levels of the drug; molecular weight of the medication; oral bioavailability of the medication in mother and infant; and protein binding of the medication. Choose medications with high protein binding (e.g., warfarin), because tissue and milk levels will be lower.
In a breastfeeding mother, milk and plasma are best regarded as ________ compartment(s), because ________. A) single / the milk: plasma ratio of most compounds is 1 B) Two separate / almost all compounds that move from plasma into milk require active transport C) A single / most compounds can move either from plasma to milk or from milk back into plasma D) Two separate / they are linked principally by passive diffusion
(D) Milk and maternal plasma should be viewed as distinct and separate compartments. For most drugs, their transfer in and out of the milk compartment is accomplished by passive diffusion. While some active transport systems exist for immunoglobulins, electrolytes, and particularly iodides, facilitated transport systems are rather limited. Indeed, fewer than 10 drugs appear to be selectively transported into human milk. As the maternal plasma level of medication increases, so does the transfer into milk. Then, as the mother metabolizes or eliminates the medication and her plasma levels begin to drop, most drugs diffuse out of the milk compartment and back into the maternal plasma compartment to be eliminated by the mother.
Which of the following psychotropic drugs has been associated with multiple adverse events that appear to be related to withdrawal, rather than medication exposure in milk? A) Citalopram B) Fluoxetine C) Paroxetine D) Venlafaxine
(D) Multiple adverse events have been reported in the literature with venlafaxine; however, most appear to be related to withdrawal rather than medication exposure in milk (Boucher et al., 2009; Tran et al., 2016).
Lipid-soluble drugs may be a good choice for a breastfeeding mother of a newborn or premature infant because those drugs: A) Produce a low milk: plasma ratio B) Typically have short half-lives C) Usually are applied topically D) Tend to be excreted in a neonate's feces
(D) Poor biliary function subsequently leads to poor lipid absorption and relative steatorrhea in newborn or premature infants. Therefore, lipid-soluble drugs, even if present in milk, would have poorer oral bioavailability in the infant. Gastric emptying time is more prolonged in premature infants and in some cases may alter the absorption kinetics altogether. The values for total body water are higher than in adults, protein binding is decreased in neonates, and the oxidative and conjugative capacity of the liver is greatly reduced in neonates.
Clinical postpartum depression is best treated by: A) medication that will increase prolactin concentration to take advantage of prolactin's calming influence B) General support, because nearly all psychotropic drugs pose some risk to the infant C) General support, because the side effects of psychotropic drugs would make adequate mothering difficult D) An antidepressant with minimal side effects, because a depressed mother may not adequately care for her infant
(D) Recent data from 17 American states indicate that postpartum depression affects 12% to 20% of women. These estimates suggest that rates have either risen or patients are reporting their symptoms more openly, as previously documented rates were between 10% and 15% (Brett, 2008; O'Hara et al., 1990). In the past, the use of antidepressants in breastfeeding mothers was discouraged. However, recent information suggests that depression itself has major negative implications for infants and that it may interfere with optimal parenting, producing significant neurobehavioral delays in infants.
Breastmilk secretion may be inhibited by: A) Metoclopramide B) Fenugreek C) Risperidone D) Progestogen
(D) Some medications are well known to affect the rate of milk production. Because infant weight gain and development are directly associated with milk production, even modest changes in milk supply can produce major growth complications for the infant. Drugs that may potentially inhibit milk production include ergot alkaloids (bromocriptine, cabergoline, ergotamine), estrogens, progestogens, pseudoephedrine, and, to a minor degree, alcohol. However, good supporting data suggesting that these agents stimulate milk production are minimal to nil. Fenugreek is the most commonly used herbal for this purpose.
The first advice to offer a mother who produces moderate to low volumes of breastmilk, and who seeks to increase those volumes, is to: A) Begin taking a dopamine antagonist such as metaclopramide B) Determine the baseline concentration of prolactin in her blood C) Be tested for insufficient thyroid D) Breastfeed or pump her breasts more frequently
(D) The dopamine antagonists are often used inappropriately to stimulate milk production in mothers with moderate to low milk production. Before these agents are employed, mothers should be advised to breastfeed more often, pump after breastfeeding, and reduce the intervals between breastfeeding. In those cases where maternal prolactin levels are already elevated, the dopamine antagonists often fail to work at all. Thus measuring baseline prolactin levels just before breastfeeding or approximately 3 hours after breastfeeding will provide an accurate estimate of the mother's trough or baseline prolactin levels; these should be somewhere above 50-70 ng/mL.
A breastfeeding infant is apt to receive a larger dosage of a maternal drug if the drug is: A) Applied topically B) Given as a single dose C) Present in low concentration in maternal plasma D) Orally bioavailable in the mother
(D) The plasma compartment is the only source of medication for the milk compartment. If drugs are not absorbed by the mother and do not produce significant plasma levels, then they pose no risk to an infant. Medications that are not orally bioavailable in the mother (e.g., oral vancomycin, magnesium hydroxide, magnesium sulfate) do not normally attain significant plasma levels and therefore are not likely to be hazardous to a breastfed infant. This group also includes most, but not all, topical preparations. Many topical steroids, antibiotics, and retinoids used over minimal surface areas are not well absorbed through the skin and are virtually undetectable in the plasma compartment. One-time injections of local anesthetics (such as for dental procedures) provide so little drug that plasma levels are minuscule. Hence, the acute use of many medications is not usually problematic, as the overall dose transferred to the infant is small over time.
A breastfeeding neonate whose mother took methodone during pregnancy: A) May suffer from neonatal abstinence syndrome after birth, despite full breastfeeding B) Will remain stable after birth because the daily dosage of the drug in breastmilk is about the same as that in utero C) Obtained through the placenta a drug dose as much as 10 times the dose through breastmilk D) Obtains through breastmilk a drug dose as much as 10 times the dose through the placenta E) May suffer drug withdrawal symptoms after birth, as well as obtain through the placenta a drug dose as much as 10 times the dose through breastmilk
(E) It should always be remembered that many neonates may have been exposed in utero to drugs taken by their mothers and that in utero exposure may be greater than that received via breastmilk. Methadone is widely used in the treatment of opiate addiction and is commonly used in pregnant patients. Methadone levels in milk depend on the dose, but generally range from 1.9% to 6.5% of the maternal dose (Begg et al., 2001; Hale & Rowe, 2017; Wojnar-Horton et al., 1997). Because of these low levels in milk, neonatal abstinence syndrome may still occur in breastfed newborns whose mothers took methadone during pregnancy (Ostrea et al., Chavez, & Strauss, 1976; Strauss et al., 1974). Because the half-life of methadone is very long, infants should be monitored for withdrawal symptoms up to 7 days following delivery or if breastfeeding is abruptly stopped.
