Transcript Drugs in Pregnancy and Lactation

Drug Therapy during
Pregnancy and Breast-Feeding
Drug Therapy during
Pregnancy and Breast-Feeding
• Purpose of this lecture is to introduce concepts and to
promote critical thinking among students
• Disclaimer: This lecture is introductory in nature and
does not attempt to comprehensively address all
clinically relevant and important considerations.
• Review of Burchum, J.R., & Rosenthal, L.D. (2016).
Drug Therapy during Pregnancy and Breast-Feeding
In Lehne’s Pharmacology for Nursing Care, 9th edition
(pp.81-87). St. Louis, Missouri: Elsevier Saunders.
• Lecture adapted by M Pinson, Winter 2016 from
powerpoint supplied by Elsevier Saunders.
• Sources of supplemental material are noted when
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relevant.
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Learning Objectives
1. Purpose: to introduce basic concepts r/t pregnancy and breastfeeding, and promote critical thinking among nursing students.
2. Understand the therapeutic goal and clinical challenges of drug
therapy during pg/BF.
3. Identify several reasons for medication use during pregnancy
4. Become familiar with general approach to drug therapy during
pg/BF
5. Become familiar with some chronic health conditions that pose
significant risk to the fetus if not managed properly.
6. Learn major physiologic changes of pregnancy that impact
maternal pharmacokinetics and may warrant dose adjustments.
7. Become familiar with types of drug-related Adverse Effects
during pregnancy
8. Define teratogenesis and teratogen. Describe dose/response
relationship, and significance of stage of fetal development and
effects of teratogen exposure.
9. Understand the purpose and limitations of FDA Pregnancy Risk Categories.
Learning Objectives, cont’d
10. Describe the basic approach and principles of drug therapy
during breastfeeding.
11. Describe several strategies for minimizing infant exposure to
drug in breast milk.
Drug Therapy during
Pregnancy and Breast-Feeding
Clinical Goal:
Provide effective treatment for mother while
avoiding harm to fetus and/or nursing infant
Clinical Challenge:
How to provide safe and effective treatment
when there is limited data on drug use during
pregnancy and breast-feeding?
Limited research data on drugs
during pregnancy and breast-feeding
• Women of reproductive age, infants and children were
historically excluded from drug research trials
• Data from adult men had to be “translated” or
“extrapolated” to pregnant/ nursing women as well as
children
• In the 1990’s, research standards shifted
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Medication use during pregnancy is common
• Pregnant and breast-feeding women use medications
for a variety of reasons
• Certain health conditions in the mother may be (are)
more dangerous to the fetus than drug(s) used to
control the condition
• Conditions that threaten the mother’s health may well
impact the fetus/baby as well
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Certain health conditions and/or risk factors that
may pose significant risks to woman and/or fetus.
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Asthma
Advanced maternal age
Anemia/ blood disorder
lifestyle choices
Diabetes
Epilepsy
Mother’s personal medical history
Hypertension
infection
Mother’s family history
pre-existing obesity
underlying mental health
conditions
http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregcomplications.htm
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http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/news/sickle-celldisease-pregnancy?page=full
Example
• Uncontrolled asthma doubles the incidence of stillbirth
among women with asthma who did not take
medications to control asthma
• Rule: avoid unnecessary drugs during pg/BF, but all
drug therapy cannot and should not be avoided
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Severe maternal morbidity (SMM)
increasing in the United States
• “Maternal morbidity” includes physical and
psychologic conditions that result from pregnancy, or
are aggravated by pregnancy, and have an adverse
effect on a woman’s health.
• The most severe complications of pregnancy,
generally referred to as severe maternal morbidity
(SMM), affect more than 50,000 women in the United
States every year. Based on recent trends, this
burden has been steadily increasing.
• Downloaded December 12, 2016 from
http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregcomplicatio
ns.htm
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Pre-pregnancy patient education on cdc.gov
“…If you are receiving treatment for a health
problem, your health care provider might want to
change the way your health problem is managed.
For example, some medicines used to treat health
problems could be harmful if taken during
pregnancy.
At the same time, stopping medicines that you
need could be more harmful than the risks posed
should you become pregnant…”
http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregcomplicati
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ons.htm
Questions so far?
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Review of Terms
■ Pharmacokinetics:
—Absorption
—Distribution
—Metabolism
—Excretion
MPinson_wi_16
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Review of Terms
■ ADME:
■ Determine the concentration of a drug at its site(s)
of action.
■ The concentration of drug at its sites of action
determines the intensity and duration of the
response.
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Review of Terms
■ Characteristics that allow molecules to cross
membranes more readily
■ ?
■ These characteristics determine how readily a drug
crosses membranes:
■ such as crossing into the placenta, entering the fetus
■ or crossing the blood-brain barrier (BBB), entering the CNS
■ Or crossing into breast-milk and being ingested by a baby
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Basic approach to drug therapy during
Pregnancy and Breast-Feeding
● Decide: should mother’s health condition be managed
with medications or not? Risk vs benefit
● Rule: Avoid drug therapy when reasonably appropriate
● Use non-pharmacological measures to promote health
when applicable/appropriate: nutrition/ fiber/ water,
physical activity, sleep, emotional support, physical
assistance, etc
● If drug therapy is indicated, then choose the drug/ regimen
with the least risk of causing harm
● Some conditions may require temporary use of a “lowest
risk” med during pg/BF, then mother can resume use of a
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different med after pg/BF if desired
Physiologic changes during pregnancy
impact pharmacokinetics.
Dose adjustments of maternal medications
may be necessary.
• Blood volume: By the third trimester, blood volume
doubles, thereby reducing the plasma concentration
of drug.
• RBF: By the third trimester, renal blood flow doubles,
thereby more rapidly eliminating renal-excreted drugs.
• Liver: For some drugs, hepatic metabolism increases
(enzyme induction), thereby decreasing amount of drug.
• Bowel: Tone & motility decrease, thereby prolonging
transit time. Increased time in the bowel allows greater
drug absorption and enterohepatic cycling to occur.
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Placental circulation: anatomic diagram
MOM
FETUS
For practical purposes, the clinician should assume
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any drug taken during pregnancy will reach the fetus
Placental drug transfer
• Essentially, all drugs can cross the placenta, but the
degree to which specific drugs enter the placenta
varies
• Factors that determine drug passage into the placenta
are the same factors that determine drug passage
across all other membranes
• For practical purposes, assume that any drug
taken during pregnancy will reach the fetus
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Drug-related Adverse Effects during pregnancy
1- Pregnant women are subject to the same adverse
effects as non-pregnant women
2- The physiologic state of being pregnant may itself
impose additional issues for mother
3- Potential adverse effects to:
● Reproductive structures (uterus, cervix, placenta)
● Fetus (organogenesis, functional development)
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Examples of drug impacts on
reproductive anatomy or fetus
• Drugs may affect uterine contractions:
– Cocaine and prostaglandins stimulate contractions
• thereby may induce abortion (ex misoprostol) or early
labor
– Aspirin can suppress contractions in labor,
but increases the risk of serious bleeding
• Drugs may cause bleeding:
• Dependence-producing drugs: babies may experience
withdrawal (abstinence syndrome) and require careful
weaning off the drug (Ex: cocaine, heroin, opiates)22
Prevent Pre-term Labor
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Baby born prematurely
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Drugs given to a pregnant women
near term/ or near delivery
• Maternal drug history is important to ongoing infant
care in the mother/baby unit or in the Neonatal
Intensive Care Unit
• Medications are sometimes given near term/ preterm
to the mother to intentionally induce fetal effects
–Ex: mothers who will give birth prematurely
(particularly prior to 36 weeks’ gestation) may be
given corticosteroids to induce more rapid
maturation of the fetal lungs
– surfactant given post-partum to baby
• By contrast, giving corticosteroids to a baby after
birth is losing favor among experts
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Potential impact of drugs on
fetal growth and development
• Teratogen = a medicine or other chemical capable of
producing a permanent structural or functional birth
defect, growth impairment, or fetal death
• Teratogenesis = the process by which congenital
malformations are produced in an embryo or fetus
− greatest concern for many
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Potential impact of drugs on
fetal growth and development
• Incidence of major structural abnormalities
(ie life-threatening or require surgical correction)
is between 1-3% of births
– half are identified at/near birth
– half are identified later or on autopsy
• Incidence of minor structural abnormalities is unknown
• Incidence of functional abnormalities is unknown
– Growth delays, learning/intellectual differences/
deficits, neurobehavioral and metabolic/ biochemical
anomalies
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Causes of birth anomalies
• About 25% - genetic factors
• Less than 1%- drugs
• Significant but unknown %- environmental
chemicals
• Vast majority of birth defects have unidentified
causes
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Effects of teratogens at various
stages of fetal development
Stage of Fetal Development
Effects of
Teratogen Exposure
Preimplantation
conception – week 2
“All or nothing”
Embryonic period
week 3 – week 8
Gross malformations,
anatomic abnormalities
Fetal period
week 9 – term
Effects are usually functional
(rather than anatomic structure)
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Teratogenesis and Stage of Development
Preimplantation
Embryonic Period
Fetal Period
Figure 9-1 Effects of teratogens at various stages of development of the fetus. (From Moore KL: The
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Developing Human: Clinically Oriented Embryology, 5th ed. Philadelphia: WB Saunders Company, 1993. With
permission.)
Teratogens
• Thought-provoking reasons why identifying
teratogens in humans is challenging
Lehne, page 82
• Minimizing the risk of teratogenesis
– 50% of pregnancies are unintended
– How can we minimize risk?
• Responding to teratogen exposure
– Informed response
– Compassion
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FDA pregnancy risk categories
The FDA established five categories (A, B, C, D, and X) to indicate a drug's
probable risk to the fetus (1979).
A - Controlled studies in women fail to demonstrate a risk to the
fetus in the first trimester, and the possibility of fetal harm
appears remote.
B - Animal studies do not indicate a risk to the fetus and there are
no controlled human studies, or animal studies do show an
adverse effect on the fetus but well-controlled studies in
pregnant women have failed to demonstrate a risk to the fetus.
C - Studies have’ shown that the drug exerts animal teratogenic or
embryocidal effects, but there are no controlled studies in
women, or no studies are available in either animals or women.
D - Positive evidence of human fetal risk exists, but benefits in
certain situations (e.g., life-threatening situations or serious
diseases for which safer drugs cannot be used or are ineffective)
may make use of the drug acceptable despite its risks.
X - Studies in animals or humans have demonstrated fetal abnormalities or there
is evidence of fetal risk based on human experience, or both, and the risk
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dearly outweighs any possible benefit.
* This organizational schema is likely to be replaced by one that provides more detailed information.
Drugs that Should Be Avoided during pregnancy
because of proven or strongly suspected teratogenicity.
Table 9-1 (p 84)
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Questions?
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Amena: example of approach to
drug therapy in pregnant woman
Case: Amena is a 28 year old Syrian refugee with a seizure
disorder who is now pregnant. She seeks treatment to
prevent seizures during the pregnancy.
Decide: treat or not to treat?
• Can the expectant woman safely go without medications
to control the condition? – No, unsafe
• Can the condition be safely managed without meds? -No
• What med does she currently use to prevent seizures?
– Carbamazepine (anticonvulsant, mood stabilizer) is in
Pregnancy Category D, and listed on Table 9-1 (p 84)
“Drugs that Should Be Avoided during pregnancy
because of proven or strongly suspected
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teratogenicity.”
Amena, page 2
• Which AED (antiepileptic drug) is best for Amena?
– Least teratogenic? And effective for her disorder?
● Research: Comparative safety of antiepileptic drugs during
pregnancy. Neurology, 2012 May 22;78(21):1692-9.
http://www.ncbi.nlm.nih.gov/pubmed/22551726
– Conclusions: AEDs such as valproate and phenobarbital were
associated with a higher risk of major malformations than
newer AEDs such as lamotrigine and levetiracetam.
Topiramate was associated with an increased risk of cleft lip
compared with that of a reference population.
● Lamotrigine = C, levetiracetam = C
– Pregnancy Category C meds pose LESS risk to fetus than
Pregnancy Category D.
● Nursing action: Discuss with provider and/or neurologist and
arrange provider-patient counseling discussion. Obtain new39
medication order as appropriate. Provide patient education.
Sherri
Case
Sherri - 28 y/o F. At primary care for referral to
antepartum care. Positive home pregnancy test, LMP 6
weeks ago.
• PMH: seasonal asthma, hypothyroidism, depression.
• Medications:
– Thyroid hormone, 125 mcg daily, for hypothyroid
– Albuterol MDI, 1-2 puffs PRN for asthma
– Flovent (fluticasone) MDI, 1 puff/day for asthma
– Zoloft (sertraline) 150 mg/d for depression
– Ibuprofen, 400 mg, PRN, for headache
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Questions?
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Drug Therapy During Breast-Feeding
“Breast milk is known to possess nutritional and
immunologic properties superior to those found in
infant formulas. An American Academy of Pediatrics
position paper emphasizes breastfeeding as the best
nutritional mode for infants for the first 6 months of
life. In addition to those qualities, studies also suggest
significant psychologic benefits of breastfeeding for
both the mother and the infant.”
~ Sumner J. Yaffe, MD, Drugs in Pregnancy and Lactation:
A Reference Guide to Fetal and Neonatal Risk
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Drug Therapy During Breast-Feeding
• Nearly all drugs can enter breast milk, but the extent of
drug entry into breast milk varies greatly
• “Fortunately, there are relatively few instances in
which drugs secreted into breast milk have been
found to cause injury to patients”…
…For the few drugs that are absolutely
contraindicated during lactation, equally effective
and safer medications are usually available”
(Adams, Holland & Urban, 2014, p 79.)
• If drug concentrations are high enough, the baby will
experience a physiologic/pharmacologic effect, raising
the possibility of harm
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• Very little systematic research
Principles of Drug Therapy During Breastfeeding
• Is the drug therapy necessary?
• What is the safest option for the infant?
• If there is the possibility of harm, monitor
infant blood levels of the drug
• Minimize infant exposure
– American Academy of Pediatrics
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Strategies to minimize infant exposure to drug
• Postpone pharmacotherapy until the baby is weaned if
possible; use nonpharm strategies when possible.
• Although most maternal medications probably pose no
harm to the breastfeeding infant, their effects have not
been fully studied.
• If drug needs to be used, then, when possible:
– Mom should take the medication immediately AFTER
feeding the baby… to reduce (if possible) the amount of
drug in the breast milk
– Avoid breast-feeding during peak effect
– Avoid drugs with long half-life or active metabolites
– Drugs that are highly protein-bound are preferred
– Use caution if baby is severely ill; a neonate; or preterm.
They may not have adequate drug metabolizing
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enzymes
Drugs Associated with Serious Adverse Effects
During Breast-Feeding
• Insert AHU, Table p 80
• And lehne p 86
• Immune suppressants (e.g., cyclosporine.
methotrexate)
• Amiodarone & antithyroid drugs
• Benzodiazepines, anticonvulsants,
antihistamine – watch for sedation
• Caffeine – high infant exposure = irritability
• All drugs of abuse, controlled substances
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Resources for further Learning: Drugs
• Drugs in Pregnancy and Lactation: A
Reference Guide to Fetal and Neonatal
Risk, 10th edition by Gerald G. Briggs
BPharm, FCCP, and Roger K. Freeman MD
• www.hsl.uw.edu
• Introduction to 9th edition was written by
Sumner J. Yaffe, MD: excellent, profound
eye-opener.
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Resources for further Learning: Herbs
• HERBS TO BE AVOIDED DURING LACTATION
Two popular herbal remedies for nursing mothers pose a
health risk to their infants.
– avoid fenugreek
– comfrey is much more dangerous; banned in Canada.
• Nursing mothers should be steered away from most herbs,
but there are some teas.
– Chicory, peppermint, orange spice and red bush tea are all fine.
Rose hips is an especially good tea because it has a very high
concentration of vitamin C.
• www.micromedexsolutions.com
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Resources for further Learning:
OB and Lactation-Specific Resources
 Association of Women's Health, Obstetric and
Neonatal Nurses www.awhonn.org
 NAACOG… NAACOG stands for Nurses'
Association of the American College of
Obstetricians and Gynecologists
 Lactation training and certification programs
 http://iblce.org/ (?)
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Patient and family-centered care
are always important
Maintaining/supporting the mental, emotional
and physical well-being of the mother
is critically important to promoting
the overall welfare of the CHILD
Fathers/partners have important roles also that
need to be supported and affirmed
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Questions?
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