Table
of Contents
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List of Contributors |
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1 |
Introduction Donald R. Mattison |
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2 |
Physiologic Changes During
Pregnancy Luis D. Pacheco, Maged M. Costantine, Gary D. V. Hankins |
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2.1 |
Physiologic changes during pregnancy |
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2.2 |
Cardiovascular system |
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2.3 |
Respiratory system |
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2.4 |
Renal system |
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2.5 |
Gastrointestinal system |
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2.6 |
Hematologic and coagulation systems |
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2.7 |
Endocrine system |
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2.8 |
Summary |
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3 |
Impact of Pregnancy on
Maternal Pharmacokinetics of Medications Mary F. Hebert |
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3.1 |
Introduction |
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3.2 |
Effects of pregnancy on pharmacokinetic parameters |
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3.2.1 |
Extraction ratio |
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3.2.2 |
Area under the concentration-time curve (AUC) |
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3.2.3 |
Bioavailability |
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3.2.4 |
Clearance |
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3.2.5 |
Protein binding |
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3.2.6 |
Organ blood flow |
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3.2.7 |
Intrinsic clearance |
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3.2.8 |
Metabolism |
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3.2.9 |
Renal |
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3.2.10 |
Volume of distribution |
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3.2.11 |
Half-life |
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3.3 |
Summary |
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4 |
Medications and the
Breastfeeding Mother Cheston M. Berlin, Jr |
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4.1 |
Medication use by the breastfeeding mother |
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4.2 |
Clinical pharmacology of drug transfer into breast milk |
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4.3 |
During delivery |
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4.4 |
General anesthesia |
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4.4.1 |
Volatile anesthetic agents |
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4.4.2 |
Intravenous anesthetic agents |
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4.4.3 |
A general statement |
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4.5 |
Epidural anesthesia |
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4.6 |
Galactogogues |
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4.7 |
Immediate postpartum period |
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4.8 |
Pain |
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4.8.1 |
Morphine |
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4.8.2 |
Codeine |
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4.8.3 |
Meperidine |
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4.8.4 |
Hydrocodone |
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4.9 |
Methadone |
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4.10 |
Resumption of pre-pregnancy medications |
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4.11 |
Psycho- and neurotropic drugs |
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4.11.1 |
Antidepressants, antipsychotics,
anxiolytics, antiepileptics,
drugs for attention deficit hyperactivity disorder |
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4.12 |
Drugs not to give to the nursing mother postpartum |
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4.13 |
Oral contraceptives (OCPs) |
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4.14 |
Summary |
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4.15 |
Where to find information |
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5 |
Fetal Drug
Therapy Erik Rytting and Mahmoud
S. Ahmed |
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5.1 |
Introduction |
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5.2 |
Indications for fetal therapy |
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5.3 |
Strategies to achieve fetal drug therapy |
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5.3.1 |
Transplacental drug transfer |
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5.3.2 |
Direct fetal injection |
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5.3.3 |
Gene therapy |
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5.3.4 |
Stem cell transplantation |
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5.3.5 |
Nanoparticles |
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5.4 |
Special considerations Acknowledgments |
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6 |
Treating the Placenta: an Evolving therapeutic
Concept Michael D. Reed and Donald H. Mattison |
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6.1 |
Introduction |
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6.2 |
The placenta as the therapeutic target: the past |
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6.2.1 |
Placental function |
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6.2.2 |
Placental transport mechanisms |
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6.3 |
The placenta: therapeutic targets |
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6.4 |
Die placenta as a therapeutic target today |
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6.4.1 |
Diabetes during pregnancy |
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6.4.2 |
Malaria in pregnancy |
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6.4.3 |
HIV-1 infection in pregnancy |
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6.5 |
The placenta as a therapeutic target in the future |
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Conclusions |
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7 |
What is Sufficient Evidence to
Justify a Multicenter Phase 3 PB Randomized
Controlled Trial in Obstetrics? Gabrielle Constdntin,
Gabriel Shapiro, Nils Chailletand
William D. Fraser |
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7.1 |
Introduction |
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7.2 |
Evidence, equipoise, and the ethical considerations in
deciding whether to conduct a trial |
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7.2.1 |
Summarizing the evidence |
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7.3 |
Why are failure rates so high for pregnancy drug trials
compared to other therapeutic areas? |
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7.4 |
Role of phase 2 trials |
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7.5 |
How to improve success rates |
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7.6 |
Learning from experience-the example of antioxidants and
preeclampsia |
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Conclusions and recommendations |
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8 |
Ethics of Clinical
Pharmacology Research in Pregnancy Marvin S. Cohen |
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Questions for further discussion |
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9 |
Pharmacogenomics in
Pregnancy David M. Haas and David A. Flockhart |
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9.1 |
Pharmacogenomics |
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9.2 |
Genetics and polymorphisms |
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9.3 |
Genes that influence pharmacokinetic variability |
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9.4 |
The current state of pharmacogenetic testing |
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9.5 |
Potential therapeutic areas for pharmacogenomics in pregnancy |
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9.6 |
Study designs and approaches to pharmacogenetics trials |
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10 |
Analgesics and
Anti-Inflammatory, General and Local Anesthetics and Muscle
Relaxants Sarah Armstrong and Roshan Fernando |
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10.1 |
Introduction |
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10.2 |
General anesthesia |
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10.3 |
Inhalational anesthetics |
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10.4 |
Intravenous anesthetics |
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10.4.1 |
Thiopentone |
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10.4.2 |
Propofol |
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10.4.3 |
Ketamine |
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10.4.4 |
Etomidate |
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10.4.5 |
Benzodiazepines |
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10.4.6 |
Systemic opioids in pregnancy |
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10.5 |
Neuromuscular blocking agents |
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10.6 |
Regional anesthesia |
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10.6.1 |
Bupivacaine |
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10.6.2 |
Lidocaine |
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10.6.3 |
2-Chloroprocaine |
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10.6.4 |
Ropivacaine |
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10.6.5 |
Adjuvant opioids |
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10.6.6 |
Fetal effects of neuraxial opioids |
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10.7 |
Summary |
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11 |
The Management of Asthma
During Pregnancy Jennifer A. Namazy and Michael Schatz |
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11.1 |
Introduction |
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11.2 |
Effect of pregnancy on the course of asthma |
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Effect of asthma on pregnancy |
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11.4 |
Asthma management |
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11.5 |
Pharmacologic therapy |
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11.5.1 |
Inhaled corticosteroids |
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11.5.2 |
Inhaled beta-agonists |
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11.5.3 |
Leukotriene modifiers |
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11.5.4 |
Cromolyn and theophylline |
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11.5.5 |
Oral corticosteroids |
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Conclusion |
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12 |
Updated Guidelines for the Management of Nausea and
Vomiting of Pregnancy and Hyperemesis Gravidarum Caroline Maltepe, Rachel Gow and Gideon Koren |
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12.1 |
Introduction |
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12.2 |
Hyperemesis gravidarum |
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12.3 |
Etiology and risk factors |
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12.4 |
Differential diagnosis |
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12.5 |
Management of NVP and HG |
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12.5.1 |
Dietary and lifestyle approaches |
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12.5.2 |
Treatment for acidity and indigestion |
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12.5.3 |
Non-pharmacological approaches |
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12.5.4 |
Pharmacological approaches |
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12.5.5 |
Management of HG |
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Conclusion |
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13 |
Clinical Pharmacology of Anti-Infectives During
Pregnancy Brookie M.
Best |
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13.1 |
Antibacterial therapy |
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13.2 |
Antifungal therapy |
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13.3 |
Malaria |
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13.4 |
Tuberculosis |
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13.5 |
HIV |
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13.6 |
Antivirals |
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13.7 |
Parasitic infections |
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14 |
Chemotherapy in
Pregnancy Caroline D. Lynch, Men-Jean Lee and Giuseppe Del Priore |
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14.1 |
Introduction |
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14.2 |
Overview of chemotherapeutic agents |
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14.2.1 |
Antimetabolites |
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14.3 |
Alkylating agents |
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14.4 |
Anthracyclines |
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14.5 |
Plant alkaloids |
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14.5.1 |
Taxanes |
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14.5.2 |
Hormonal agents |
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14.6 |
Targeted therapies |
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14.7 |
Other agents |
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14.8 |
Treatment of specific cancers |
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14.9 |
Breast cancer |
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14.10 |
Lymphoma |
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14.11 |
Leukemia |
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14.12 |
Ovarian cancer |
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14.13 |
Future fertility |
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14.14 |
Pharmacokinetics in pregnancy |
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15 |
Substance Use
Disorders James J. Nocon |
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15.1 |
Introduction |
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15.2 |
Substance use disorders defined |
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15.3 |
Addiction defined as a disease of the brain |
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15.4 |
The good news; the brain can recover |
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15.5 |
Pregnancy enhances recovery |
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15.6 |
Addiction in women and pregnancy |
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15.7 |
Psychiatric co-morbidity |
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15.8 |
Substances used |
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15.8.1 |
Alcohol |
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15.8.2 |
Tobacco; nicotine |
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15.8.3 |
Opiates and opioids |
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15.8.4 |
Fentanyl |
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15.8.5 |
Benzodiaepines |
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15.8.6 |
Marijuana; THC |
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15.8.7 |
Cocaine |
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15.8.8 |
Stimulants: amphetamine, methamphetamine; methyl phenidate; ephedra; khat |
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15.8.9 |
Hallicinogens: lysergic acid diethylamide and phencydidine |
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15.8.10 |
Club drugs: MDMA;flunitrazepam;
gamma-hydroxybuterate; ketamine |
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15.9 |
Screening and detection |
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15.10 |
The role of urine and meconium
testing |
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15.11 |
Brief office screening strategies |
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15.12 |
Brief office interventions |
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15.13 |
Long-term care and maintenance |
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Conclusion |
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16 |
Diabetes in Pregnancy Maisa N. Feghali,
Rita W. Driggers, Menachem
Miodovnik and Jason G. Umans |
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16.1 |
Introduction |
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16.2 |
Epidemiology |
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16.3 |
Classification |
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16.4 |
Gestational diabetes |
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16.5 |
Diabetes management in pregnancy |
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16.5.1 |
Nutritional goals and exercise |
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16.5.2 |
Glucose monitoring and glycemic
control |
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16.5.3 |
Insulin therapy |
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16.5.4 |
Oral hypoglycemics |
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16.5.5 |
Postpartum metabolic management |
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Conclusion |
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17 |
Cardiovascular Medications in
Pregnancy Thomas R. Easterling |
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17.1 |
Introduction |
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17.2 |
Cardiovascular changes in pregnancy |
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17.3 |
Cardiovascular diseases in pregnancy |
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17.4 |
Pharmacodynamics of hemodynamically
active drugs in pregnancy |
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17.5 |
Fetal pharmacodynamic response
to hemodynamically active drugs |
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17.6 |
Direct fetal effects of hemodynamically
active drugs |
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17.7 |
Pharmacokinetic changes in hemodynamically
active drugs in pregnancy |
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Key points |
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18 |
Antidepressants in
Pregnancy Elizabeth M. LaRusso andMarlene P. Freeman |
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18.1 |
Introduction |
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18.2 |
Effects of untreated perinatal
depression on women and children |
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18.3 |
Approach to treatment |
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18.4 |
Potential risks of selective serotonin reuptake
inhibitor (SSRI) use during pregnancy |
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18.4.1 |
Obstetric outcomes |
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18.4.2 |
Congenital malformations |
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18.4.3 |
Persistent pulmonary hypertension of the newborn (PPHN) |
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18.4.4 |
Poor neonatal adaptation |
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18.4.5 |
Neurodevelopmental outcomes |
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18.5 |
Potential risks of non-SSRI antidepressant use during
pregnancy |
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18.6 |
Potential risks of older antidepressant use during
pregnancy |
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18.7 |
Anxiety |
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18.8 |
Summary |
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19 |
Uterine Contraction Agents and
Tocolytics Courtney D. Cuppett
and Steve N. Caritis |
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19.1 |
Introduction |
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19.2 |
Uterine contraction agents (uterotonics) |
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19.2.1 |
Pitocin (oxytocin) |
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19.2.2 |
Methergine (methylergonovine) |
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19.2.3 |
Prostaglandins |
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19.2.4 |
Uterotonics summary |
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19.3 |
Uterine relaxation agents (tocolytics) |
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19.3.1 |
Magnesium sulfate (MgSO4) |
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19.3.2 |
p-Adrenergic-receptor agonists |
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19.3.3 |
Nitric oxide donors |
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19.3.4 |
Calcium channel blockers |
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19.3.5 |
Cydooxygenase inhibitors (COX inhibitors) |
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19.3.6 |
Oxytocin receptor antagonists (atosiban) |
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19.3.7 |
Tocolytics summary |
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20 |
Thyroid Disease and Pharmacotherapy Pill
Pregnancy Shannon M.
Clark and Gary D.V. Hankins |
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20.1 |
Thyroid function and physiology in pregnancy |
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20.2 |
Hyperthyroidism in pregnancy |
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20.3 |
Pharmacotherapy with thionamrdes
in pregnancy |
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20.4 |
Hypolhyroidism in pregnancy |
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20.5 |
Pharmacotherapy with levothyroxine
in pregnancy |
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20.6 |
Summary |
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21 |
Dermatological Medications and Local
Therapeutics Maria-Magdalena Roth and Caius
Solovan |
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21.1 |
Introduction |
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21.2 |
Acne |
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21.2.1 |
Systemic treatment for acne |
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21.2.2 |
Local treatment for acne |
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21.3 |
Psoriasis |
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21.3.1 |
Systemic treatment for psoriasis |
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21.3.2 |
Local treatment for psoriasis |
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21.3.3 |
Phototherapy |
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21.4 |
Bacterial infections |
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21.4.1 |
Systemic treatment of bacterial infections |
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21.4.2 |
Local treatment of bacterial infections |
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21.5 |
Viral infections |
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21.5.1 |
Systemic treatment of viral infections |
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21.5.2 |
Local treatment of viral infections |
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21.6 |
Fungal infections |
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21.6.1 |
Systemic treatment for fungal infections |
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21.6.2 |
Local treatment for fungal infections |
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21.7 |
Parasitic infections |
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21.7.1 |
Systemic and local treatment for parasitic infections |
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21.8 |
Antipruritics |
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21.8.1 |
Systemic antipruritics |
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21.8.2 |
Local antipruritics |
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21.9 |
Glucocorticosteroids |
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21.9.1 |
Systemic glucocorticosteroids |
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21.9.2 |
Local glucocorticosteroids |
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21.10 |
Immunomodulators/immunosuppressive therapy |
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21.11 |
Analgesics |
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21.11.1 |
Systemic analgesics |
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21.11.2 |
Local analgesics (Anesthesia) |
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21.12 |
Antiseptics (disinfectants) |
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22 |
Vitamins, Minerals, Trace
Elements, and Dietary Supplements Jean-Jacques Dugoua |
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22.1 |
Introduction |
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22.2 |
First trimester |
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22.2.1 |
Vitamin B6 (pyridoxine) |
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22.2.2 |
Vitamin B9 (folic acid) |
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22.2.3 |
Vitamin A |
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22.2.4 |
Vitamin E |
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22.2.5 |
Calcium |
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22.3 |
Second trimester |
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22.3.1 |
Calcium |
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22.3.2 |
Vitamins C, E, and zinc |
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22.3.3 |
Chromium |
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22.3.4 |
Coenzyme Q10(CoQ10) |
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22.4 |
Third trimester |
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22.4.1 |
Castor oil (Ricinus communis) |
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23 |
Herbs and Alternative
Remedies Henry M. Hess |
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23.1 |
Herbal teas frequently used during pregnancy |
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23.2 |
Essential oils used as aromatherapy during pregnancy |
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23.3 |
Herbs used as capsules or dried extracts |
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23.3.1 |
Ginger |
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23.3.2 |
Cranberry |
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23.3.3 |
Echinacea |
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23.3.4 |
St. John’s wort |
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23.3.5 |
Valerian |
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23.3.6 |
Milk thistle/silymarin |
|
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23.3.7 |
Senna |
|
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23.3.8 |
Horse chestnut |
|
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23.4 |
Herbal topical preparations used in pregnancy |
|
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23.4.1 |
Aloe vera gel |
|
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23.4.2 |
Horse chestnut |
|
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23.5 |
Non-herbal supplements used in pregnancy |
|
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23.5.1 |
Fish oils |
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23.5.2 |
Probiotics |
|
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23.6 |
Herbs used to induce labor |
|
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23.7 |
Acupuncture and acupressure therapy in pregnancy |
|
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23.8 |
Meditation and hypnosis in pregnancy |
|
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24 |
Envenomations and Antivenoms During Pregnancy Steffen A. Brown and William F.
Rayburn |
|
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24.1 |
General principles about envenomation |
|
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24.2 |
Snake bites |
|
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24.2.1 |
Management during pregnancy |
|
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24.2.2 |
Reports during pregnancy |
|
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24.3 |
Spider bites |
|
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24.3.1 |
Management during pregnancy |
|
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24.3.2 |
Reports during pregnancy |
|
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24.4 |
Scorpion stings |
|
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24.4.1 |
Management during pregnancy |
|
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24.4.2 |
Reports during pregnancy |
|
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24.5 |
Hymenoptera |
|
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24.5.1 |
Winged hymenoptera |
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24.5.2 |
Imported fire ants |
|
|
24.5.3 |
Management during pregnancy |
|
|
24.5.4 |
Reports during pregnancy |
|
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24.6 |
Jellyfish |
|
|
24.6.1 |
Management during pregnancy |
|
|
24.6.2 |
Reports during pregnancy |
|
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24.7 |
Antrvenom use during pregnancy |
|
|
|
Conclusions |
|
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25 |
Gastrointestinal
Disorders Noel Lee, Veronika Gagovic
and Sumona Saha |
|
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25.1 |
Gastroesophageal reflux disease |
|
|
25.1.1 |
Treatment |
|
|
25.1.2 |
Antacids |
|
|
25.1.3 |
Sucralfate |
|
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25.1.4 |
Promotilrty agents |
|
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25.1.5 |
H2-Receptor antagonists |
|
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25.1.6 |
Proton pump inhibitors |
|
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25.2 |
Peptic ulcer disease |
|
|
25.2.1 |
Treatment |
|
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25.3 |
Constipation |
|
|
25.3.1 |
Treatment |
|
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25.4 |
Diarrhea |
|
|
25.4.1 |
Treatment |
|
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25.5 |
Abdominal pain |
|
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25.6 |
Gastrointestinal infections |
|
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25.7 |
Inflammatory bowel disease |
|
|
25.7.1 |
Treatment |
|
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25.8 |
Hepatitis B |
|
|
25.8.1 |
Treatment |
|
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25.9 |
Hepatitis C |
|
|
25.9.1 |
Treatment |
|
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25.10 |
Wilson’s disease |
|
|
25.10.1 |
Treatment |
|
|
25.11 |
Autoimmune hepatitis |
|
|
25.12 |
Intrahepatic cholestasis
of pregnancy |
|
|
25.13 |
Primary biliary cirrhosis and
primary sclerosing cholangitis |
|
|
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|
