Pregnancy and Lactation
The duration of pregnancy is approximately 280 days; this time period extends from the first day of the last menstrual period to birth. Pregnancy is divided into three periods of three calendar months; each 3-month period is called a trimester.
Drug absorption during pregnancy can be affected by a decrease in gastrointestinal motility, an increase in gastric pH, and an increase in pulmonary alveolar drug uptake.
Drug distribution during pregnancy may change because maternal plasma volume increases by 50%. However, the net impact on drug distribution for many (not all) drugs is an unaltered free-drug serum concentration. Notable exceptions of drugs for which the unbound fraction increases significantly include salicylic acid, sulfisoxazole, diazepam, valproic acid, and phenytoin.
Drug elimination during pregnancy is affected in various ways. Maternal hormones enhance the hepatic metabolism for some drugs (e.g., phenytoin) and inhibit it for others (e.g., theophylline). In addition, the clearance of drugs excreted into the biliary system may be slow. Renal drug clearance may be affected by an increase in renal flood flow and glomerular filtration rate. Fortunately, these changes usually do not result in a clinically significant alteration requiring a change in drug dosing.
The placenta is the organ of exchange between the mother and fetus for a number of substances, including drugs. It is generally thought that drug exposure during the embryonic period (the fifth through tenth week of gestation) has the greatest potential influence on organ development. Drug exposure at other times during pregnancy may be associated with subtle changes in function or behavior.
Drugs Selection During Pregnancy :
- The incidence of congenital malformation is approximately 3% to 5%, and it is estimated that 1% of all birth defects are caused by medication exposure.
- Adverse fetal drug effects depend on dosage, route of administration, concomitant exposure to other agents, and stage of pregnancy.
- Medications associated with teratogenic effects in the period of organogenesis (18 to 60 days postconception) include methotrexate, cyclophosphamide, diethylstilbesterol, lithium, retinoids, thalidomide, certain antiepileptic drugs, and coumarin derivatives.
- Medications which may cause adverse fetal effects in the second or third trimesters include angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory agents, and tetracycline derivatives.
- Principles that may be helpful in selecting medications for use during pregnancy include selecting drugs that have been used safely for long periods of time and prescribing drug doses at the lower end of the dosing range. Also, pregnant women should be discouraged from self-medication.
Preconception Planning :
- Preconception interventions have been shown to improve pregnancy outcomes.
- Ingestion of folic acid (400 mcg/day) by all women of childbearing potential reduces the risk for neural tube defects in offspring.
- Women who have had a child with a neural tube defect or who use certain seizure medications should receive 4000 mcg of folic acid daily beginning 1 to 3 months prior to conception and continuing throughout the first trimester.
- Screening and immunization for rubella and varicella; screening for and treatment of sexually transmitted diseases (STDs); and assessment and reduction in the use of alcohol, tobacco, and other substances prior to pregnancy all improve outcomes.
- Behavioral therapy with or without nicotine replacement therapy may help women quit smoking before and during pregnancy.
Pregnancy Influenced Issues :
- Constipation commonly occurs during pregnancy. Nondrug modalities such as education, physical exercise, biofeedback, and increased intake of dietary fiber and fluid should be instituted first.
- If additional therapy is warranted, the use of supplemental fiber with or without a stool softener is appropriate.
- Castor oil and mineral oil should be avoided.
Gastroesophageal Reflux Disease
- Therapy includes lifestyle and dietary modifications such as small, frequent meals; caffeine avoidance; food avoidance 3 hours before bedtime; and elevation of the head of the bed.
- Drug therapy, if necessary, may be initiated with aluminum, calcium, or magnesium antacids; sucralfate; or cimetidine or ranitidine. Lansoprazole and metoclopramide are also options if the patient does not respond to histamine-2 receptor blockers.
- Sodium bicarbonate and magnesium trisilicate should be avoided.
- Hemorrhoids during pregnancy are common.
- Therapy includes high intake of dietary fiber, adequate oral fluid intake, use of sitz baths; topical anesthetics, skin protectants and astringents may also be used. Treatment for refractory hemorrhoids includes rubber band ligation, sclerotherapy, and surgery.
Nausea and Vomiting
- Up to 80% of all pregnant women experience some degree of nausea and vomiting. Hyperemesis gravidarum (i.e., severe nausea and vomiting requiring hospitalization for hydration and nutrition) occurs in only about 0.5% of pregnant women.
- Nonpharmacologic treatments include eating small, frequent meals; avoiding fatty and fibrous foods; acupressure and acustimulation. Pharmacotherapy may include the following: antihistamines (e.g., doxylamine), vitamins (e.g., pyridoxine, cyanocobalamin), anticholinergics (e.g., dicyclomine, scopolamine), dopamine antagonists (e.g., phenothiazines, metoclopramide), ondansetron, and ginger.
GESTATIONAL DIABETES MELLITUS
- Screening for gestational diabetes mellitus utilizes the oral glucose challenge test.
- First-line therapy includes nutritional and exercise interventions for all women, and caloric restrictions for obese women. If first-line therapy fails to achieve fasting whole blood glucose levels less than or equal to 95 mg/dL and 2-hour postprandial levels less than or equal to 120 mg/dL, then therapy with recombinant human insulin should be instituted; glyburide may be considered after 11 weeks of gestation.
- Goals for self-monitored blood glucose levels while on insulin therapy are a preprandial plasma glucose level between 80 and 110 mg/dL, and a 2-hour postprandial plasma glucose level less than 155 mg/dL.
- Hypertension during pregnancy includes chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and preeclampsia superimposed on chronic hypertension. Preeclampsia-eclampsia is a syndrome consisting of gestational blood pressure elevation with proteinuria (i.e., greater than or equal to 300 mg in a 24-hour urine collection). Preeclampsia-eclampsia is suspected in the absence of proteinuria if the woman has gestational blood pressure elevation with blurred vision, abdominal pain, headache, thrombocytopenia, or elevated liver enzymes. Eclampsia is preeclampsia with seizures.
- For women at high risk for preeclampsia, aspirin, 50 to 150 mg/day, reduced rates of perinatal death and preeclampsia, reduced rates of spontaneous preterm birth and increased mean birth weight. Calcium may also benefit these high-risk women.
- Antihypertensive drug therapy for gestational hypertension or preeclampsia has not been shown to improve fetal outcomes. First-line therapy for mild to moderate hypertension in pregnancy is methyldopa. Alternatives include labetolol and other Î² blockers (except atenolol), prazosin, nifedipine, isradipine, hydralazine, and clonidine.
- The cure for preeclampsia is delivery of the fetus if the pregnancy is at term. Parenteral hydralazine and labetolol in addition to oral nifedipine for hypertension and magnesium sulfate for seizure prevention are standard therapy for acute severe hypertension in preeclampsia.
- Risk factors for venous thromboembolism in pregnancy include increasing age, history of thromboembolism, hypercoaguable conditions, operative vaginal delivery or cesarean section, obesity, and a family history of thrombosis.
- Low-molecular-weight heparins are the preferred treatment for prophylaxis or treatment of venous thromboembolism during pregnancy. Unfractionated heparin may also be used, but is associated with more side effects. Warfarin should be avoided after the first 6 weeks of gestation because it may cause fetal bleeding, malformations of the nose, stippled epiphyses, or central nervous system anomalies.
ACUTE CARE ISSUES IN PREGNANCY
- For tension headaches during pregnancy, nonpharmacologic approaches are first-line therapies, including rest, reassurance, and ice applications.
- For migraine and tension headaches, acetaminophen is the drug of first choice for pain.
- Nonsteroidal anti-inflammatory drugs are contraindicated after 37 weeks’ gestation. For refractory migraines, narcotics may be used. The use of Sumatriptan is controversial. Nausea of migraines may be treated with metoclopramide.
URINARY TRACT INFECTION
- The principle infecting organism is Escherichia coli, but Proteus mirabilis and Klebsiella pneumoniae account for some infections. Untreated bacteriuria may result in pyelonephritis, preterm labor, and low birth weight.
- Group B Streptococcus bacteriuria should be treated when discovered to reduce the rate of preterm delivery. These women should also receive antibiotics at delivery to prevent infection in the newborn.
- Ampicillin or amoxicillin are considered safe medications during pregnancy, but resistance to these drugs may occur in up to 20% to 30% of isolates. Alternatives include nitrofurantoin and cephalexin.
- Sulfa-containing drugs should be avoided during the third trimester; folate antagonists, such as trimethoprim, are relatively contraindicated during the first trimester; and fluoroquinolones and tetracyclines are contraindicated throughout pregnancy. Courses of treatment of 7 to 10 days are common, and a repeat culture to confirm cure is recommended.
SEXUALLY TRANSMITTED DISEASE
- It is important to distinguish STDs that are bacterial in origin from those that are viral in origin because microbiologic cure is the usual end point of therapy for bacterial infections, whereas control of outbreaks at the time of delivery is the end point for viral infections.