Chapter 36 Pain Management during Pregnancy and Lactation Flashcards
KEY POINTS 1. Pain is frequent during pregnancy and lactation. Many women suffer from pelvic girdle pain and back pain. 2. Physiologic changes during pregnancy may alter drug pharmacokinetics and pharmacodynamics. 3. Most drugs cross the placenta and cross into breast milk. 4. Drug effects on the fetus may be direct or indirect (effect on the mother). 5. Efforts should be made to minimize maternal exposure to drugs during pregnancy and lactation. 6. Possible adverse effects of in utero dr
Diffusion
primarily passive and the drug concentration in the umbilical vein or breast milk depends on the concentration gradient, drug lipid solubility, degree of ionization and protein binding, and the diffusion capacity of the membrane (this may change as pregnancy progresses).
The effects of the drugs on
the fetus or nursing child will depend on
the gestational or postconceptual age, as well as the amount and duration of
drug exposure, and the specific drug
physiologic changes of pregnancy influence
drug absorption, distribution, and elimination
Changes in gastrointestinal function can alter oral drug absorption. Renal elimination is generally increased because of
an increase in glomerular filtration rate. Hepatic metabolism may be increased, unchanged, or decreased, and the increase in total body water may alter drug distribution
and peak concentrations. Protein binding is usually
decreased; however, the free drug concentration may be
unchanged because of increased drug clearance.
The amount of drug that crosses the placenta depends on
maternal cardiac output, fetal cardiac output, placental binding, and placental metabolism, as well as factors that influence passive diffusion across the placenta
Maternal plasma levels of a drug depend on
the site of administration
(e.g., oral, intravascular, or epidural space), the total dose,
the dosing interval, and other drugs that may be co-administered (e.g., epinephrine)
The amount of drug to which
the fetus is exposed also depends on
fetal metabolism (fetal
blood carrying drugs away from the placenta passes first through the fetal liver), fetal protein binding (about half of
maternal protein binding), and the distribution of fetal
cardiac output (fetal distress results in redistribution of
blood flow to the vital organs).
Possible adverse effects on the fetus of in utero drug exposure include
structural malformations, intrauterine fetal death, altered fetal growth, neurobehavioral teratogenicity, acute neonatal intoxication or neonatal abstinence syndromes
A major determinant of the effect of a drug on the
fetus is the
gestational age of the fetus.
The period of classic teratogenesis
corresponds with the critical period of organogenesis and begins approximately 31 days after the first day of the last menstrual period until about 71 days after the last period.
fetal drug exposure at this
time is not risk free.
Fetal development, particularly the central nervous system,
continues into the second and third trimesters, and
indeed after birth.
U.S. Food and Drug Administration Pregnancy Category System - A
Adequate, well-controlled studies in pregnant women have not shown
an increased risk of fetal abnormalities
U.S. Food and Drug Administration Pregnancy Category System- B
Animal studies have revealed no harm to the fetus; however, there are no
adequate and well-controlled studies in pregnant women. Or animal studies
have shown an adverse effect, but adequate and well-controlled studies in
pregnant women have failed to demonstrate a risk to the fetus
U.S. Food and Drug Administration Pregnancy Category System- C
Animal studies have shown adverse fetal effects and there are no adequate
and well-controlled studies in pregnant women. Or no animal studies have
been conducted and there are no adequate and well-controlled studies in
pregnant women.
U.S. Food and Drug Administration Pregnancy Category System- D
Studies, adequate and well controlled or observational, in pregnant women
have demonstrated a risk to the fetus. However, the benefits of therapy may
outweigh the potential risk.
U.S. Food and Drug Administration Pregnancy Category System- X
Studies, adequate and well controlled or observational, in animals and pregnant
women have demonstrated positive evidence of fetal abnormalities. The use of
the product is contraindicated in women who are or may become pregnant.
U.S. Food and Drug Administration Pregnancy Category System- B
Drugs
Acetaminophen; butorphanol, nalbuphine; caffeine; fentanyl,* methadone,* meperidine,*
morphine,* oxycodone,* oxymorphone;* ibuprofen, naproxen, indomethacin;
prednisone, prednisolone
U.S. Food and Drug Administration Pregnancy Category System- C
Drugs
Amitriptyline; aspirin, ketorolac; betamethasone, cortisone; codeine,* propoxyphene,* hydrocodone;* gabapentin; lidocaine; propranolol; sumatriptan; sertraline, fluoxetine; bupropion
U.S. Food and Drug Administration Pregnancy Category System- D
Drugs
Imipramine; carbamazepine; diazepam; paroxetine; phenobarbital; phenytoin,
valproic acid
U.S. Food and Drug Administration Pregnancy Category System- X
Drugs
Ergotamine
Aspirin use during pregnancy may be associated with an
increased risk of
gastroschisis. Pregnant women should not use aspirin (.150 mg/day) regularly.
Ibuprofen and
naproxen during the first trimester
do not appear to be
teratogenic
Prostaglandin inhibitors have been associated with
narrowing of the ductus arteriosus in utero. Aspirin and
other prostaglandin inhibitors may decrease amniotic fluid
volume secondary to decreased fetal urine output, and they may prolong pregnancy and labor.
An increased incidence
of neonatal intracranial hemorrhage has been found in premature infants whose mothers ingested
aspirin near birth. For these reasons, full-dose aspirin and nonsteroidal antiinflammatory
drug (NSAID) therapy should be avoided in the third trimester. If a mild analgesic is indicated during pregnancy, acetaminophen is the drug of choice.
maternal opioid agonist or
agonist–antagonist exposure during pregnancy
There is no evidence that maternal opioid agonist or
agonist–antagonist exposure during pregnancy is teratogenic
Chronic in-utero exposure to opioids may lead to
neonatal abstinence syndrome.
treat mild or moderate pain during pregnancy
Acetaminophen combined
with hydrocodone or oxycodone may be used
maternal steroid use associated with
orofacial clefts
tricyclic
antidepressant drugs are
no evidence that tricyclic
antidepressant drugs are teratogenic
Exposure to SSRIs in the third
trimester before delivery may lead to a
neonatal withdrawal syndrome, and transient QT interval prolongation. An increased risk of persistent pulmonary hypertension syndrome
of the newborn
The anticonvulsants phenytoin, carbamazepine, and valproic acid all have been associated with
fetal dysmorphic
syndromes and should only be used when the risk
outweighs the benefit
Why is Ergotamine is contraindicated in pregnancy,
it may
be teratogenic, and it also causes uterine contractions
beta-blockers
they may be associated with intrauterine growth
retardation
amount of drug to which an infant is exposed during
lactation- Maternal factors
maternal dose and dosing interval, the elimination half-life of the drug, the infant nursing pattern (volume and timing), and the amount of drug that actually crosses into breast milk.
The milk to plasma (M:P) ratio
is an index of the amount of drug that
is excreted into breast milk
Breast milk is slightly more
acidic than plasma, and therefore
passive diffusion favors
drugs that are weak bases, lipid soluble, and have low protein binding
volume of drugs in colostrum
Because the volume of colostrum is small, nursing neonates are exposed to minimal amounts of the drugs
administered to the mother in the postpartum period.
minimize infant exposure.
Administration of drugs shortly after nursing, and avoiding long-acting drugs
The following should
be considered when prescribing drugs to lactating
women
Is drug therapy really necessary?
The safest drug should be chosen, such as acetaminophen rather than aspirin for mild analgesia.
If there is a possibility of risk to the infant, then one should consider monitoring infant serum levels of the drug.
Having the mother take the medication just after she
has breast fed the infant or before the infant is due to
sleep can minimize drug exposure.
Acetaminophen
considered the safest analgesic for nursing mothers. The infant of a mother taking acetaminophen 4 g/day was exposed to less than 5% the
therapeutic infant dose
Opioid agonist and agonist–antagonists
cross freely into breast milk
opioids
compatible with breastfeeding
meperidine
Patient-controlled intravenous meperidine administered
for postcesarean delivery analgesia had a negative impact on neonatal neurobehavioral scores compared to morphine. The infants of nursing mothers ingesting opioids, particularly meperidine, should be monitored for adverse effects.
prednisone
Less than 1% of the maternal dose of prednisone or
prednisolone is recovered in breast milk.2 Even at high
maternal doses, this is unlikely to be enough to suppress
infant adrenal function
anticonvulsants
The anticonvulsants carbamazepine, phenytoin, and
valproic acid may be used safely during lactation
Risk Categories for Drugs for Nursing Infants -Drugs for which the effect on nursing infants is unknown but may
be of concern
Benzodiazepines, tricyclic antidepressants, buproprion, fluoxetine
Risk Categories for Drugs for Nursing Infants- Drugs that have been associated with significant effects on some
nursing infants and should be given to nursing mothers with caution
Aspirin, ergotamine
Risk Categories for Drugs for Nursing Infants- Maternal medication usually compatible with breast-feeding
Acetaminophen, anticonvulsants, beta-blockers, local anesthetics,
nonsteroidal anti-inflammatory drugs, opioid agonists, opioid
agonists–antagonists, steriods, sumatriptan, sertraline, paroxetine
Ergotamine
has been associated with neonatal convulsions and gastrointestinal disturbances and should not be used in nursing mothers
The two factors that determine the possible effects of radiation exposure on the developing fetus
gestational age and fetal dose of absorbed radiation.
Risks of fetal radiation exposure
abortion, genetic mutation,
and carcinogenesis
At doses of less than 50 mGy,
the risk of abnormalities is thought to be negligible; significant risk of malformation is increased only at doses
greater than 150 mGy
exposure should be avoided if possible until after
Although radiation exposure
from imaging studies generally falls below 50 mGy, exposure should be avoided if possible until after the 15th week of gestation since radiation can be lethal to the fetus or cause severe defects with doses as low as 50 mGy
MRI is indicated during
pregnancy when
other nonionizing imaging methods, such as ultrasonography, are unsatisfactory, and the information obtained would otherwise require exposure to ionizing
radiation
pelvic girdle pain
used to describe pain in the symphysis pubis and/or pain
in the regions of one or both sacroiliac (SI) joints and the
gluteal region, whereas pregnancy-related low back pain refers to pain in the lumbar region
Risk factors of pelvic girdle pain
strenuous work, previous low back pain, or pain syndromes in a previous pregnancy.
etiology of pelvic girdle pain
may be related to mechanical,
traumatic, hormonal, metabolic, or degenerative changes during pregnancy. Pain usually begins in the second trimester and resolves for most women
within several weeks to months of delivery.
Pelvic girdle pain is usually located between
the posterior
iliac crests near the SI joints.
treatments of pelvic girdle pain
Patient eduction, pelvic belts,
physiotherapy,and acupunture may be of benefit to some
patients
Medication of pelvic girdle pain
Acetaminophen is the drug of choice for minor pelvic and back pain. The short-term use of NSAIDs may be appropriate during the first and second trimesters. Severe back pain may require opioid therapy.
Epidural steroid injection(s) may be indicated for acute radicular pain consistent with lumbar nerve root
compression
