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Clinical - Winter > 18 - Pregnancy & Lactation > Flashcards

18 - Pregnancy & Lactation Flashcards

1
Q

What percentage of pregnant women take medication during their pregnancy?

A

60%

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2
Q

What percent of pregnancies in North America are unplanned?

A

Around 50%

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3
Q

What are the problems w/ medication use in pregnancy?

A
  • First physician visit often weeks into pregnancy
  • Lack of into on safety of medications in pregnancy
  • Societal beliefs (exaggerated perception of risk leads to increased rate of abortion)
  • Litigation (overly cautious approach by HCPs)
  • Risks to mother/fetus of not taking medications
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4
Q

What are some conditions that may require drug use during pregnancy?

A
  • N/V of pregnancy
  • Cough, cold, allergic rhinitis
  • UTI
  • Hypertension, preeclampsia
  • Gestational diabetes
  • Asthma
  • Depression
  • Epilepsy
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5
Q

What is a teratogen? Give examples

A
  • Agent that acts to irreversibly alter growth, structure, or function of the developing embryo or fetus
  • Ex: viruses, environmental factors, chemicals, drugs
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6
Q

What is teratology?

A
  • Study of birth defects

- Looks at the causes, mechanisms, and patterns of abnormal development

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7
Q

What was thalidomide marketed as for pregnant women?

A

Sedative/anxiolytic and for morning sickness

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8
Q

What effect did thalidomide have on developing fetuses?

A
  • Limb malformations

- Ear, CV, GI anomalies

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9
Q

What period of gestation do upper limbs form?

A

27-30 days

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10
Q

What period of gestation do lower limbs form?

A

30-33 days

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11
Q

Exposure to a teratogen during ___ gestation will cause a duodenal atresia (absence or abnormal narrowing)

A

40-47 days

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12
Q

What period during pregnancy is the embryo/fetus most at risk from exposure to teratogens?

A

2-8 weeks after conception

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13
Q

What is the pre-implantation period of pregnancy?

A
  • Time from conception to implantation (first 2 weeks)
  • All or nothing phenomenon (if the embryo is exposed to a teratogen, it will either kill it or it will recover w/ no harm)
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14
Q

What is the embryonic period of pregnancy? What occurs during this phase?

A
  • 2-8 weeks post conception
  • Organogenesis (development of organs and specialized tissues)
  • Greatest period of vulnerability to teratogens
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15
Q

What is the fetal period of pregnancy?

A
  • 9 weeks to birth
  • Period of growth and maturation of organs
  • Anomalies can still occur
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16
Q

Which drugs have potential adverse effects of spontaneous abortion?

A
  • Warfarin
  • Toluene
  • Cocaine
  • NSAIDs
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17
Q

Which drugs have potential adverse effects of congenital anomalies?

A
  • Anticonvulsants
  • Isotretinoin
  • Lithium
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18
Q

Which drugs have potential adverse effects of fetal growth restriction?

A
  • Beta blockers

- Nicotine

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19
Q

What are the mechanisms of fetal toxicity?

A
  • Receptor-ligand interactions
  • Covalent bonding
  • Peroxidation of lipids and proteins
  • Interference/inhibition of protein and enzyme function
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20
Q

What are some physiological changes that occur in the mother during pregnancy that affect pharmacokinetics?

A
  • Decreased gastric motility (affects absorption)
  • Increased maternal blood volume and decreased plasma protein (affect distribution)
  • Altered liver activity (affects metabolism)
  • Increased renal blood flow (affects excretion)
  • Decreased AUC, peak plasma and SS concentration, t1/2, and increased clearance in about 50% of drugs
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21
Q

How do the majority of drugs cross the placenta?

A

Passive diffusion

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22
Q

What are characteristics of a drug that is likely to cross the placenta?

A
  • Lipophilic
  • Unionized
  • Low molecular weight
  • Low protein binding
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23
Q

What is the criteria for a compound to be considered teratogenic?

A
  • Defect can be characterized
  • Drug proven to be able to cross placenta
  • Exposure occurs during critical development period for the specific defect
  • Association is biologically possible
  • Consistent epidemiological findings
  • Teratogenicity in animals (not always a direct correlation)
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24
Q

What are some known teratogenic drugs?

A
  • Alcohol
  • ACE inhibitors
  • Isotretinoin
  • Lithium
  • Methotrexate
  • Phenytoin
  • Thalidomide
  • Valproic acid
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25
Q

What teratogenic effect do anticonvulsants have?

A
  • Neural tube defects

- Craniofacial anomalies, cleft palate

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26
Q

What teratogenic effect do ACE inhibitors have?

A
  • CV malformations
  • Microcephaly
  • Spina bifida
  • Renal failure, death
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27
Q

What teratogenic effect do coumadin derivatives have?

A
  • “Warfarin syndrome” = hypoplasia of nose/extremities, eye abnormalities, scoliosis, deafness
  • Fetal hemorrhage
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28
Q

What teratogenic effect does methotrexate have?

A
  • Craniofacial, skeletal malformations

- Neural defects, mental retardation

29
Q

What teratogenic effect does isotretinoin have?

A
  • Craniofacial abnormalities
  • Cardiac defects, hydrocephalus
  • Spontaneous abortion
30
Q

What are the signs and symptoms of fetal alcohol syndrome?

A
  • Dysmorphic features (small eye openings, flattened cheekbones, indistinct philtrum)
  • Prenatal/postnatal growth retardation
  • Cognitive deficits
  • Behavioural and learning problems
31
Q

Is there a correlation to amount smoked during pregnancy and birth weight of the child?

A

Yes, more cigarettes = lower birth weight

32
Q

What are the various FDA categories for teratogens?

A
  • Class A = controlled studies showed no risk to humans
  • Class B = no evidence of risk in humans
  • Class C = risks can’t be ruled out in humans
  • Class D = clear evidence of risk in humans (benefits may outweigh the potential risk)
  • Class X = drugs contraindicated in human pregnancy
33
Q

What are some drawbacks of FDA classifications? What should be concluded?

A
  • Often based on limited data (animal studies, case-report, limited or no human data)
  • Infrequently updated
  • Inconsistent assignment (some teratogens or those w/ serious fetal effects listed as C or D)
  • Over simplifies a complex topic
  • Don’t use outdated FDA classifications
34
Q

Which source is used by majority of OB/GYN and physicians?

A

Briggs (drugs in pregnancy and lactation)

35
Q

What are the new changes to FDA labelling rules?

A
  • 3 sections – pregnancy, lactation, and females and males of reproductive potential
  • Pregnancy – summary of risk of adverse developmental outcomes on all relevant data; risk of disease, dose adjustments, maternal adverse effects
  • Applies to all new drugs, and older drugs phased in gradually
  • OTCs not included
36
Q

What is the role of the pharmacist when dealing w/ teratogenic drugs?

A
  • Discuss risk for women of child-bearing age BEFORE they become pregnant
  • Discuss risk to mother and unborn infant if condition untreated
  • Consider non-pharm options
37
Q

What should be done if therapy w/ a teratogenic drug is required?

A
  • Monotherapy at lowest effective dose for shortest amount of time
  • Older drugs w/ more information generally preferred
38
Q

What is the role of the pharmacist after a teratogenic drug has been used in pregnancy?

A
  • Determine timing of exposure
  • Review available information (don’t rely on old FDA classifications)
  • Discuss relative risk (may only be 1-2% above basline; population birth defect rate is 1-3%)
  • Consult prescribed for further background info if required
  • Consider referral to information center (ex: MotherRisk)
39
Q

What are some benefits to breastfeeding?

A
  • Ideal nutrients that can’t be replicated by formula
  • Lower rate of infections
  • Decreased incidence of SIDS
  • Enhanced neurocognitive performance
  • Benefits for mother
40
Q

How can drugs transfer into breast milk?

A
  • Transcellular diffusion – small unionized lipid soluble molecules transverse capillary wall
  • Intercellular (paracellular) diffusion – large molecules avoid alveolar cell entirely (spaces are larger during earlier stages of breastfeeding)
  • Ionophore – polar molecules enter via binding to carrier proteins w/in cell membrane
41
Q

What are some drug properties that affect transport into breast milk?

A
  • Molecular size (better chance if less than 200-300 daltons)
  • Ionization (must be unionized)
  • Lipid solubility (better chance if highly lipophilic)
  • Plasma protein binding (better chance if poorly protein bound)
  • pKa
42
Q

What can happen to basic drugs w/ higher pKa w/ respect to breast milk? What happens to acidic drugs?

A
  • Greater amount of ionized drug will be in milk, thus “trapped” (must be unionized to cross lipid membrane)
  • Can result in milk/plasma ratio > 1
  • Opposite effect for acidic drugs (more in plasma)
43
Q

What drug factors should be considered when determining use during lactation?

A
  • Amount transferred into breast milk
  • Type of drug and adverse effect profile (ex: increased BP vs. diarrhea)
  • PK properties (high bioavailability = more absorbed by infant; long half life = greater chance of accumulation)
  • Prescribed for infants? and relative infant dose
44
Q

What patient factors should be considered when determining use during lactation?

A
  • Indication (essential? other alternatives available?)
  • Duration of therapy (greater risk of accumulation w/ prolonged tx)
  • Underlying conditions (ex: renal dysfunction)
  • Age of infant and ADME
45
Q

What is the milk/plasma ratio? What value is given when drug concentrates in milk to a large degree?

A
  • Drug concentration in milk / drug concentration in plasma

- Values over 1-5

46
Q

How can infant dosage and daily dose be calculated using drug concentration in mothers milk?

A
  • Infant dosage = drug concentration in milk * volume of milk
  • Daily dose = average drug concentration in milk * volume of milk ingested in 24 h
47
Q

What is the most common calculation done for expressing actual drug exposure in lactation? How is it calculated? What is an ideal value?

A
  • Relative infant dose
  • [Infant dose (mg/kg/day) / maternal dose (mg/kg/day)] * 100
  • RID under 10% generally considered safe
48
Q

Which antibiotics are concerning during lactation?

A

Tetracyclines and fluoroquinolones

49
Q

Are acetaminophen and NSAIDs safe in breastfeeding?

A
  • Acetaminophen yes

- NSAIDs yes except ASA

50
Q

Can opioids be used during lactation?

A
  • Morphine, methadone and hydromorphone considered safe
  • Codeine safe unless mother is an ultra-metabolizer
  • Caution w/ oxycodone, and meperidine
51
Q

Can antidepressants and antipsychotics be used during lactation?

A
  • SSRIs compatible (sertraline, paroxetine, fluvoxamine, and fluoxetine less preferred)
  • Tricyclic antidepressants are safe (avoid doxepin)
  • Atypical antipsychotics are less studied
  • Lithium has a high RID, but can be used if no other option
52
Q

Can BZDs be used during lactation?

A
  • Lorazepam is compatible
  • Diazepam is okay for short-term use
  • Choose drugs w/ short t1/2 and duration
53
Q

Can vaccines be given during lactation?

A

Yes, except yellow fever vaccine

54
Q

Can alcohol be consumed by the mother during lactation?

A
  • Yes
  • Avoid chronic use
  • Delay breastfeeding 2 hours after drink
55
Q

Is smoking safe during lactation?

A

No, should be avoided (increased risk of SIDS)

56
Q

What are galactagogues used for?

A
  • Stimulate lactation

- Dopamine antagonists that stimulate prolactin production

57
Q

Which drugs should be used w/ caution in lactation?

A
  • Amiodarone
  • Certain beta blockers (atenolol, sotalol)
  • Lamotrigine
  • Lithium
  • Mycophenolate
58
Q

Which drugs are contraindicated in lactation?

A
  • Cytotoxic (antineoplastic) drugs
  • Radiopharmaceuticals
  • Drugs which inhibit lactation (bromocriptine, cabergoline, ergotamine)
59
Q

What are some strategies to minimize exposure to harmful drugs during lactation?

A
  • Choose drug w/ favourable properties/kinetics
  • Time doses right after breastfeeding
  • Minimize dose and duration
  • Monitor SE and drug levels
  • Consider alternative drug or non-pharm measures
60
Q

What is the cause of morning sickness?

A
  • Unknown, some theories include:
  • Hormonal changes (elevated hCG)
  • Changes in GI motility (delayed gastric emptying and decreased esophageal sphincter tone)
  • H. pylori infection
61
Q

What is the course of N/V in pregnancy?

A
  • Begins around 4-6 weeks
  • Peaks between 7-12 weeks
  • Lessens by 12-20 weeks
  • Onset after 8-10 weeks rare (red flag)
62
Q

What is hyperemesis gravidarum? What is the tx?

A
  • Persistent, intractable vomiting

- May require hospitalization if dehydration occurs

63
Q

What are some risk factors for N/V during pregnancy?

A
  • Multiple pregnancy
  • NVP in previous pregnancy
  • Familial history
  • Molar pregnancy
  • History of GI problems
  • History of migraines
64
Q

What are some non-pharms for N/V in pregnancy?

A
  • Eat small amounts of food every 1-2 h
  • Separate solids and liquid by ~ 30 mins
  • Minimize spicy, fried, or high-fat foods
  • Maintain adequate fluid intake (2 litres/day)
  • Avoid strong smells
65
Q

What is pyridoxine? Is it safe to use for N/V in pregnancy?

A
  • Vitamin B6

- May be useful for mild to moderate N/V

66
Q

What are the ingredients of Diclectin? What are some SE?

A
  • 10 mg of each doxylamine and pyridozine (1st gen antihistamine and vitamin B6)
  • SE = sedation, anticholinergic
67
Q

When would dimenhydrinate or diphenhydramine be used for N/V in pregnancy?

A

For breakthrough sx for women on Diclectin

68
Q

When would metoclopramide be used for N/V in pregnancy?

A

Severe cases

69
Q

When should N/V in pregnancy be referred?

A
  • Unable to keep food/water down for more than 24 h
  • Significant weight loss
  • Signs of dehydration (increased thirst, decreased urination, dry mouth)
  • Signs of infection
  • Other sx inconsistent w/ N/V (neurlogical, hematemesis, abdominal pain)
  • Onset after 10 weeks or return of sx

Clinical - Winter (24 decks)

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