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Thera X > 5 Drugs in Pregnancy and Lactation Briggs > Flashcards

5 Drugs in Pregnancy and Lactation Briggs Flashcards

1
Q

What time frame is the First Trimester?

A

0-14 weeks (0 starts at the first day of last menstrual cycle)

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2
Q

What time frame is the Second Trimester?

A

15-28 weeks

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3
Q

What time frame is the Third Trimester?

A

29-42 weeks

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4
Q

For physiologic changes in pregnancy for the mother, what happens with her blood volume?

A

Increased throughout; average increase from nonpregnant state is 40-45%

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5
Q

For physiologic changes in pregnancy for the mother, what happens with her cardiovascular function?

A

Decreased blood pressure and vascular resistance; increased stroke volume and cardiac output

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6
Q

For physiologic changes in pregnancy for the mother, what happens with her pulmonary function?

A

Increased tidal volume, minute ventilatory volume, and oxygen uptake; decreased residual capacity and residual air volume; dyspnea is common

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7
Q

For physiologic changes in pregnancy for the mother, what happens with her Renal Function?

A

Marked increase in renal blood flow and GFR; 40-80% above nonpregnant patient. Decreased renal vascular resistance. Mean GFR 150 mL/min (may be > 200). No PK equations apply to pregnant patients

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8
Q

For physiologic changes in pregnancy for the mother, what happens with her GI Tract?

A

Delayed gastric emptying. Decreased intestinal motility (increased transient times). Altered taste and appetite. Nausea and vomiting, heartburn, and constipation are common

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9
Q

For physiologic changes in pregnancy for the mother, what happens with her Hepatic Function?

A

Increased hepatic blood flow. Many changes in activity of liver enzymes. Decreased serum albumin concentration but binding and total amount unchanged. Decreased bilirubin

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10
Q

For physiologic changes in pregnancy for the mother, what happens with her Coagulation?

A

Marked increase in levels of clotting factors. Increased plasminogen maintains equilibrium of clotting and lysing activity. Thromboembolism is leading cause of maternal death. Postpartum period has highest risk compared to pregnancy - 5 times higher for venous clot and 15 times higher for pulmonary embolism

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11
Q

What are some drugs that can cause Infertility?

A

Busulfan. Chlorambucil. Cyclophosphamide. Mechlorethamine. Melphalan

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12
Q

What are some common drugs for Gestational HTN-Preeclampsia-Eclampsia?

A

MgSO4, Labetalol, Methyldopa

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13
Q

What are Prostaglandins used for?

A

Cervical ripening (misoprostol or dinoprostone)

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14
Q

What are Oxytocics used for?

A

Induction of labor (oxytocin)

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15
Q

What kind of analgesics are preferred during labor and delivery?

A

Regional analgesia preferred - systemic not effective

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16
Q

What types of drugs can cause growth alterations?

A

B-blockers, Ethanol, Corticosteroids, Cigarettes, Diabetes

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17
Q

What types of drugs can cause Function - Neurobehavior deficits?

A

Ethanol, Cigarettes, Marijuana, N2O, SSRIs

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18
Q

What are the characteristics of Spontaneous Abortion?

A

Before 20 weeks’ gestation; background risk is 15-20%; most caused by chromosome abnormalities

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19
Q

What is a Stillbirth?

A

After 20 weeks’ gestation; peak incidence is in 3rd trimester; most caused by placental abruption; other causes are maternal obesity, diabetes, etc

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20
Q

What types of infections can cause birth defects?

A

Toxoplasma gondii, Treponema pallidum. These can also kill the fetus

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21
Q

What types of viruses can cause birth defects?

A

CMV, herpes simplex 1 and 2, Parvovirus B-19, Rubella, Varicella zoster, Venezuelan equine encephalitis

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22
Q

What accounts for > 90% of environmental birth defects?

A

Maternal diabetes

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23
Q

What is the most critical factor for determining if an adverse outcome was d/t a drug exposure?

A

Time of exposure

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24
Q

What is the most vulnerable period for birth defects and drug exposure?

A

Organogenesis (embryogenesis)

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25
Q

Why is timing critical?

A

If exposure occurs after structure is formed, it cannot cause defect

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26
Q

What time period can neural tube defects occur?

A

17-30 days

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27
Q

What is No Observed Effect Level (NOEL)?

A

Threshold dose below which there is no developmental toxicity

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28
Q

What drugs have a NOEL?

A

Thalidomide (50-100 mg/day); Atenolol (< 50mg/day); Paroxetine (< 25mg/day)

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29
Q

Which drugs have no known NOEL?

A

Ethanol, Isotretinoin (Accutane), Glucose

30
Q

At what A1c does the rate of defects greatly increase?

A

> 7.2%

31
Q

Why are so many major structural anomalies found later?

A

Most infants are not examined by a pediatrician trained to find hidden birth defects or identify clusters of minor defects. A cluster of 3 or more defects is an indicator for a hidden major defect

32
Q

When are most functional/neurobehavioral deficits recognized?

A

Usually not until at least 5 years of age

33
Q

What are ACE-I and Angiotensin II Blockers like for birth defects?

A

CP: 2nd and 3rd trimesters. RM: Dose/duration dependent. DT: Renal failure, oligohydraminios, Iugr, SB, Hypocalvaria (fetus), Renal failure (NB), Hypotension (NB)

34
Q

What are Androgenic Hormones like for birth defects?

A

CP: Labial fusion (8th-13th weeks), clitoral hypertrophy (2nd and 3rd trimesters). RM: Unknown. DT: Masculinization of female fetus

35
Q

What are 1st Gen Anticonvulsants like for birth defects?

A

CP: 1st trimester (structural defects), 3rd Trimester (hemorrhagic disease of newborn). RM: 2-3x background risk with epilepsy alone. Folic acid 4-5mg/day may reduce risk for all agents except VPA

36
Q

What is Lamotrigine (Lamictal) like for birth defects?

A

2nd Gen Anticonvulsant. Crosses human placenta. Highly teratogenic

37
Q

*The cause of MOST birth defects is thought to be what?

A

Gene-environment interaction

38
Q

What are Systemic Corticosteroids like for birth defects?

A

CP: Oral clefts (> 10 weeks), growth restriction (throughout). RM: Oral clefts 2-7x background risk, effect on growth requires prolonged therapy. DT: Cleft lip +/- plate, growth restriction (300-400g)

39
Q

What is Cardioselective (B1) agent growth restriction like?

A

Atenolol has most data. 2nd and 3rd trimesters. Dose and duration dependent. HTN potentiates ADRs. Decreased placental weight, decreased birth weight; IUGR (lower placental perfusion secondary increased vascular resistance)

40
Q

What is Diethylstilbestrol like for birth defects?

A

CP: 10-18 weeks (vaginal adenocarcinoma), up to 20 weeks (genital defects). RM: Cervical or vaginal structure defects. DT: Female and male genital defects; infertility; increased SABs, ectopic pg, preterm birth

41
Q

What is Iodine like for birth defects?

A

CP: 2nd and 3rd trimesters. RM: Dose and duration dependent. DT: Hypothyroidism, goiter

42
Q

What is Lithium like for birth defects?

A

CP: 1st trimester (cardiac defects), 3rd trimester (newborn toxicity). RM: Cardiac effects, Ebstein’s anomaly (downward displacement of tricuspid valve into right ventricle)

43
Q

What are NSAIDs like for birth defects?

A

CP: Early 1st trimester, > 32 weeks (premature closure of ductus arteriosus and renal toxicity). RM: Unknown. DT: SAB, cardiac, renal toxicity, persistent pulmonary HTN

44
Q

What are SSRIs like for birth defects?

A

CP: 1st trimester (birth defects, SAB), > 20 weeks (withdrawal, PPHN). RM: About 30% for neonatal withdrawal. Greatest risk w/ Paroxetine (most defects are ventricular septal defects)

45
Q

What is the neonatal toxicity after prolonged in utero exposure to SSRIs?

A

Respiratory distress. Abstinence syndrome (increased irritability and crying, decreased sleep, vomiting, watery stools, decreased weight gain)

46
Q

What are Vitamin A Derivatives (Acitretin - Etretinate, Isotretinoin) like for birth defects?

A

One of the top 3 causes of birth defects. DP: Days 14 after conception to end of 1st trimester. DT: SAB, CNS, craniofacial, cardiovascular, thymus gland

47
Q

What is Warfarin like for birth defects?

A

CP: 6th-9th week (FWS) throughout (CNS defects). DT: FWS (nasal/epiphyses), CNS, optic, cardiac, IUGR

48
Q

What is Alcohol like for birth defects?

A

CP: Throughout. RM: NO SAFE DOSE. DT: IUGR, MR, facial anomalies (Classic Triad), Microcephaly, Multiple defects, Long-term neurobehavior abnormalities

49
Q

What is Cigarette smoking like for birth defects?

A

CP: 1st trimester (malformations, SAB), 2nd and 3rd trimester (growth)

50
Q

What is the dose dependent toxicity with cigarette smoking?

A

SAB. Decreased weight. Neurodevelopment - mental retardation. Impaired neonatal lung function. Retinal vessel defects (reversible). Infantile colic

51
Q

What is cigarette smokings effect on pregnancy?

A

Reduced fertility. Ectopic (tubal) pregnancies. Abnormal placentation. Premature rupture of membranes. Preterm delivery. Perinatal mortality

52
Q

What does the amount of drug reaching embryo/fetus depend on?

A

Maternal concentration! Elimination half-life! Lipid solubility. Protein binding. Ionization at physiologic pH. KEY: Drugs can cross back to mother

53
Q

What is the “Placental Barrier”?

A

Consists entirely of fetal tissue, trophoblast, connective tissue, capillary endothelium

54
Q

When would a drug be considered low risk?

A

If it did not produce adverse effects in animals at a dose < 10x the human dose (based on BSA or AUC)

55
Q

What is the Colostral Phase?

A

Postpartum days 0-4. Junctions (pores) between mammary epithelium and cells are relatively open

56
Q

What is Colostrum?

A

37-169mL during first 48 hrs. Rich in immunoglobulins and antioxidants

57
Q

What can medications do before 4 weeks postpartum?

A

Medications or stopping/starting breastfeeding may adversely effect milk production

58
Q

What can medications do after 4 weeks postpartum?

A

Lactation well established; resistant to disruption

59
Q

What are drugs passages into milk like?

A

Small water-soluble nonelectrolytes (simple diffusion into milk through pores in mammary epithelial membrane). Larger molecules (cross mammary epithelium through cell into milk; passive diffusion down concentration gradient). Ion trapping of BASIC drugs (milk pH < plasma). Drugs rarely reach equilibrium between blood and milk because breasts are constantly being emptied by infant

60
Q

What is the average milk intake?

A

150 mL/kg/day

61
Q

What are acceptable drug concentrations into breast milk?

A

< 10% of maternal dose

62
Q

What are caution drug concentrations into breast milk?

A

10-25% of maternal dose

63
Q

What are unacceptable drug concentrations into breast milk?

A

> 25% of maternal dose. Inherent toxicity. Credible reported toxicity

64
Q

What are the general characteristics of ADRs in infants from breast milk?

A

Most reported toxicity occurs in first 4 weeks after birth. Slower elimination of drug from neonate compared with older infants. Nearly all reported toxicity observed in infants at 6 months of age or younger

65
Q

Why are Anti-anxiety agents, antidepressants, and antipsychotics drugs of concern?

A

These agents are of concern because they are given for long periods and could alter short-term and long-term CNS function

66
Q

What is the concern with codeine use?

A

Ultra-rapid metabolizers create more of the active morphine form, allowing more to get to the baby (which can’t eliminate it).

67
Q

What can “pump and dump” be used for?

A

Maternal comfort. Maintaining milk supply waiting for drug to be eliminated from mother

68
Q

What is the MOST important factor for determining if a drug caused a birth defect?

A

Time of exposure

69
Q

What is the dose of alcohol considered low-risk in pregnancy?

A

A NOEL has not been observed

70
Q

The FDA requires that all new drugs have at LEAST what informatino?

A

Animal reproduction data

71
Q

Which drug types would be expected to have the HIGHEST M:P ratio?

A

Basic drugs

72
Q

A nursing infant at what age is at GREATEST risk for an adverse reaction from a drug in milk?

A

3 weeks

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