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Clinical Pharmacy > Drugs in Pregnancy and Lactation > Flashcards

Drugs in Pregnancy and Lactation Flashcards

1
Q

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

A
  • nausea and vomiting
  • cough/cold and allergic rhinitis
  • prenatal supplementation
  • UTI
  • hypertension/preeclampsia
  • gestational diabetes
  • asthma
  • depression
  • epilepsy
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2
Q

What is a teratogen?

A
  • agents that act to irreversibly alter growth, structure or function of the developing embryo or fetus
  • derived for the greek word “teratos” meaning monster
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3
Q

What is the definition of teratology?

A
  • the study of birth defects

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

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4
Q

What are some of the most common causes of birth defects?

A
  • teratogens include viruses, environmental factors, chemicals and drugs
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5
Q

Describe the thalidomide tragedy?

A
  • marketed as a sedative/anxiolytic and for morning sickness in pregnancy
  • no defects in animals
  • several years before birth defects linked to thalidomide and withdrawal of drug from the market
  • causes limb malformations, ear, cardiovascular, GI anomalies
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6
Q

What is the pre-implantation period?

A
  • time from conception to implantation - first 2 weeks
  • characterized by all or nothing phenomenon
  • significant insult will cause death
  • generally not the cause of malformations
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7
Q

What is the embryonic period?

A
  • defined as 2-8 weeks post conception
  • organogenesis - development of the organs and specialized tissues
  • formation of the organs occur at different times
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8
Q

What is the greatest period of vulnerability to teratogens?

A
  • embryonic period
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9
Q

What is the fetal period?

A
  • 9 weeks to birth
  • period of growth and maturation or organs
  • anomalies can still occur
  • — we always need to know the timing of exposure
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10
Q

What drugs can cause a spontaneous abortion?

A
  • warfarin
  • toluene
  • cocaine
  • NSAIDs
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11
Q

What drugs can cause congenital anomalies?

A
  • anticonvulsants
  • isotretinoin
  • lithium
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12
Q

What drugs can cause growth restriction?

A
  • beta blockers

- nicotine

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13
Q

What are the different mechanisms of toxicity?

A
  • receptor ligand interactions (includes receptors for hormones, growth factors, etc)
  • covalent bonding (binds to endogenous molecule forming a DNA or protein complex)
  • peroxidation of lipids and proteins
  • interference/ inhibition of protein and enzyme function (methotrexate on dihydrofolate reductase- can lead to a folate deficiency and a neural tube defect)
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14
Q

Why is there a decreased absorption of drugs in pregnancy?

A
  • decrease in gastric motility
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15
Q

Why is there an increased distribution in pregnancy?

A
  • increase in maternal blood volume, decrease in plasma protein
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16
Q

What is the effect of an increased excretion of drugs in pregnancy? Why is this?

A
  • there is an increased secretion of drugs due to an increase in renal blood flow
  • clearance goes up and the half life goes down
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17
Q

The majority of placental drugs cross via _______

A

passive diffusion

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18
Q

A drug is more likely to cross the placenta if it is what?

A
  • lipophilic
  • unionized
  • has a low molecular weight (< 500-600 Da)
  • low protein binding
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19
Q

What are the maternal factors that will influence placental drug delivery?

A
  • placental blood flow

- placental metabolism

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20
Q

What is the criteria to name something a potential teratogen?

A
  • defect can be characterized
  • drug proven to be able to cross the placenta
  • exposure occurred during the critical development period for the specific defect
  • association must be biologically possible
  • consistent epidemiological findings
  • teratogenicity in animals
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21
Q

What are some of the most common teratogenic drugs?

A
  • alcohol
  • ACE inhibitors
  • amiodarone
  • carbamazepine
  • coumadin
  • cyclosphosphamide
  • diethylstillbestrol
  • isotretinoin
  • litium
  • methotrexate
  • misoprostal
  • paroxetine
  • phenytoin
  • tetracyclin
  • valproic acid
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22
Q

What is the effect of using an anticonvulsant in pregnancy?

A
  • can cause neural tube defects

- craniofacial anomalies, cleft palate

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23
Q

What is the effect of using an ACE inhibitor in pregnancy?

A
  • cardiovascular malformations, microcephaly, spina bifida
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24
Q

What is the effect of coumadin derivatives in pregnancy?

A
  • hypoplasia of nose/extremities, eye abnormalities, IUGR, scoliosis, deafness, and mental retardation
  • fetal hemorrhage
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25
Q

What is the effect of using methotrexate in pregnancy?

A
  • craniofacial and skeletal malformations

- neural defects, mental retardation

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26
Q

What is the effect of using isotretinoin in pregnancy?

A
  • craniofacial abnormalities

- cardiac defects, hydrocephalus, spontaneous abortion

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27
Q

What is the effect of alcoholic pregnancy?

A
  • passes easily through the placenta, delayed clearance from the fetus
  • fetal alcohol syndrome- dysmorphic features (small eye openings, flattened cheekbones, indistinct philtre), prenatal/postanatal growth retardation, cognitive deficits, behavioural and learning problems
  • also effects heart, kidneys, eyes and skeletal
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28
Q

What is the effect of cigarettes to the placenta?

A
  • toxic to the embryo and the fetus
  • vasoactive effect and reduced oxygen levels
  • cleft lip and palate
  • direct dose response reduction in fetal growth
    • newborns of mothers who smoke weigh an average of 200 g less than nonsmokers
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29
Q

What is the effect of caffeine on the fetus?

A
  • findings are unclear and inconsistent

- greater risk of miscarriage with doses over 300 mg/day

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30
Q

What are the main drawbacks of FDA classifications in pregnancy?

A
  • often based on limited data (animal studies, case reports, limited or no human data)
  • infrequently updated
  • inconsistent assignment
  • over simplifies a complex topic and doesn’t take into account
31
Q

What is the major role of the pharmacist in communicating with pregnancy?

A
  • include discussion of risk when counselling for women of child-bearing age for drugs with significant teratogenic potential
  • discuss risk to mother and unborn infant if condition is treated
  • consider non-pharm options
  • need to determine the timing of exposure
  • review the available information
  • consult prescriber if further background is required
32
Q

What things should be considered if therapy is required in pregnant women?

A
  • mono therapy at lowest effective dose for shortest amount of time
  • older drugs with more information generally preferred
  • do other drugs in the same class carry less risk?
33
Q

What is the brig’s classification of ibuprofen?

A
  • cannot give at all in 1st and 3rd trimester
  • they are associated with pulmonary hypertension in 3rd trimester and spontaneous abortion with cardiac defects, oral clefts and gastroschisis in the 1st trimester
34
Q

What are the benefits of breastfeeding?

A
  • ideal nutrients that cannot be replaced by formula
  • lower rate of infection
  • decreased incidence of SIDS
  • enhanced neurocognitive performance
  • also benefits for mother
35
Q

What is the effect of codeine in breastfeeding women?

A
  • extensively used for postpartum pain
  • minor excretion of codeine and morphine into breast milk
  • metabolized by CYP2D6 liver enzymes to morphine
  • CYP2D6 displays significant genetic polymorphism(ultra-rapid metabolizers)
  • greater risk to the infant after 4 days
36
Q

What are the 3 ways that drugs transfer into breast milk?

A
  1. Transcellular: transverse capillary wall; small un-ionized lipid soluble molecules
  2. Intercellular (paracellular): avoids alveolar cell entirely- large molecules lg, cow milk protein
  3. Ionophore: polar molecules enter via binding to carrier proteins within cell membrane
37
Q

What are the different drug properties that affect the transportation of drugs into the breast milk?

A
  • molecular size
  • un-ionized
  • lipid solubility
  • plasma protein binding
  • pKa
    (has the greatest chance to enter the breast milk if it is less than 200-300 Da, poorly protein bound or highly lipophilic)
38
Q

What is ion trapping?

A
  • non-ionized forms of molecules pass easily from the lipid membrane
  • basic drugs with a higher pKa- generally there is a greater amount of ionized molecules in milk, therefore it is trapped
  • can result in a milk/plasma ratio of >1
  • opposite effect for acidic drugs
  • ionized drugs are “trapped” and cannot pass back through the membrane
39
Q

A high oral bioavailability means that ____ drug is absorbed by the infant

A

more

40
Q

A longer half life means that there is a _____ chance of accumulation

A

greater

41
Q

What are the different drug factors that need to be considered before we give a drug to someone?

A
  • amount transferred into the breast milk
  • type of drug and adverse effect profile
  • pharmacokinetic properties
  • is this drug generally prescribed for infants
42
Q

What are the different patient factors to consider when determining if a drug is safe with lactation?

A
  • indication
  • duration of therapy (greater risk of accumulation with prolonged treatment)
  • underlying conditions
  • age of infant and ADME (decreased kidney and liver function, greater relative total body water, higher pH (increased absorption of some drugs), less protein binding)
43
Q

What are the ideal medication properties in breastfeeding mothers?

A
  • large molecule
  • poor lipid solubility
  • low oral bioavailability
  • highly protein bound
  • short half life
  • weak acid
  • minimal side effects
  • used in infants
44
Q

How do you calculate milk/plasma ratio?

A

drug concentration in milk/drug concentration in plasma

45
Q

What does a high milk/plasma ratio mean?

A
  • high values suggest that drug concentrations in milk to large degree (does not provide information about amount of drug transferred)
46
Q

How do you calculate the infant dosage?

A
  • drug concentration in milk x volume of milk
47
Q

How do you calculate the daily dose?

A
  • average drug concentration in milk x volume of milk ingested in 24 hours
48
Q

Are SSRIs compatible in pregnancy?

A
  • yes, it is considered compatible
  • sertraline, paroxetine and fluvoxamine
  • fluoxetine is less preferred
49
Q

Are tricyclics compatible in pregnancy?

A
  • generally low RID

- doxepin- avoid accumulation of active metabolite

50
Q

What is the safety of atypical antipsychotics in pregnancy?

A
  • less studied
51
Q

What is the safety of lithium in pregnancy?

A
  • RID 12-30%, use if there is no other options, monitor levels
52
Q

The higher the RID, the ______

A

less safe in pregnancy

53
Q

What kind of benzos should be chosen in pregnancy?

A
  • choose drugs with a short half life and a short course of action
54
Q

How should vaccines be used in pregnancy?

A
  • they are compatible
  • maternal antibodies can be found in milk, but there is no effect on infant response
  • exception- yellow fever vaccine
55
Q

Large doses of alcohol can decrease _________

A

milk production

56
Q

What happens to the baby when there is a lot of alcohol consumed while breastfeeding?

A
  • avoid chronic use- psychomotor development is delayed

- casual use is acceptable though, delay breastfeeding 2 hours after a drink

57
Q

What are galactagogues used for?

A
  • used to stimulate lactation
  • dopamine antagonists stimulate prolactin production
  • they are safe- have a low RID
58
Q

What is the action of fenugreek as a galactagogues?

A
  • questionable efficacy

- safety is poorly studied

59
Q

What drugs should be cautioned in lactation?

A
  • amiodarone
  • certain beta blockers (atenolol and sotalol)
  • lamotrigine (may reach therapeutic plasma levels, decreased metabolism)
  • lithium
  • mycophenolate
60
Q

What drugs are absolutely contraindicated in lactation?

A
  • cytotoxic drugs
  • radiopharmaceuticals
  • drugs that inhibit lactation (bromocriptine, cabergoline, ergotamine)
61
Q

What are some common strategies that minimize exposure in lactation?

A
  • choose drugs with favourable kinetics
  • time doses right after breastfeeding
  • minimize dose and duration
  • monitor SE and drug levels
  • consider alternative drug or non-pharm measures
62
Q

What are some of the causes of nausea and vomiting in pregnancy?

A
  • unknown
  • hormonal changes (elevated human gonadotropin peak in the first trimester. Levels found to be higher in women with hyperemesis)
  • changes in GI motility (delayed gastric emptying, decreased esophageal sphincter tone)
  • H. pylori infection
63
Q

What are the symptoms and course of morning sickness?

A
  • nausea, vomiting and retching
  • can occur any time of the day, not just morning
  • vomitus - non bilious and no blood
    Course :
  • begins around 4-6 weeks
  • most severe between 7-12 weeks
  • lessens by 12- 20 weeks
  • affects 20% of women
  • onset after 8-10 weeks rare
64
Q

What is hyperemesis gravidarum ?

A
  • incidence: 0.5-2%
  • persistent, intractable vomiting
  • dehydration, >5% weight loss, electrolyte abnormalities, ketosis
  • may require hospitalization
65
Q

What are the goals of therapy associated with morning sickness?

A
  • control of sx (prevent worsening, improve functioning and quality of life)
  • maintain adequate fetal and maternal nutrition
  • prevent dehydration
66
Q

What are some of the non-pharm managements of treating morning sickness?

A
  • eat small amounts of food every 1-2 hours
  • separate solids and liquids about 30 minutes
  • try dry, bland or salty foods high in carbohydrates
  • minimize spicy, fried or high-fat foods
  • snack on high protein foods
  • maintain adequate fluid intake - 2 litres/day; drink cold or take ice chips, popsicles, slushies
  • avoid strong smells
  • reduce iron supplement intake (1st trimester only)
67
Q

What are the non-pharm managements of morning sickness?

A
  • ginger- increases gastric tone
  • dose: 500-1000 mg/day divided QID
  • short term studies- more effective than placebo, as effective as B6
  • acupuncture/acupressure
  • hypnosis
68
Q

What are some of the pharmacological management of morning sickness?

A
  1. pyridoxine (vitamin B6)
    - dose: 40-100 mg/day
    - conflicting evidence, may be useful for mild to moderate NVP
  2. Thiamine (vitamin B1)
    - ineffective for NVP
    - useful for preventing deficiency in prolonged severe NVP
  3. Doxylamine/pyridoxine
69
Q

What is doxylamine/pyridoxine?

A
  • a 1st generation antihistamine and vitamin B6
  • first drug of choice in N/V
  • diclectin is the trade name
70
Q

What is the efficacy of diclectin?

A
  • there was a decreased emesis and increased well being compared to placebo in those taking diclectin
71
Q

What are the AE of diclectin?

A
  • sedation, anticholinergic
72
Q

What are the drugs that are used for breakthrough N/V in pregnancy?

A
  • dimenhydrinate, diphenhydramine

- metoclopramide is reserved for more severe cases

73
Q

When should ondansetron be used in those with morning sickness?

A
  • often used in chemotherapy for N/V

- use only if other options are ineffective (can cause QT prolongation)

74
Q

When should you refer for morning sickness in pregnancy?

A
  • unable to keep food/water down > 24 hours
  • significant weight loss
  • signs of dehydration (increased thirst, dry mouth, weakness)
  • signs of infection
  • other symptoms inconsistent with NVP (neurological, hematemesis, abdominal pain)
  • onset of NVP after 10 weeks or return of symptoms

Clinical Pharmacy (24 decks)

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