161 babies were adversely affected by thalidomide.<\/p>\n\n\n\n
- Special physiological condition<\/li>
- Total avoidance of pharmacological treatment is not possible<\/li>
- New medical problems (Gest diab, PIH) can develop and old ones can be exacerbated<\/li>
- Pregnancy may modify maternal response to drugs, Some effects such as phocomelia seen immed\u2026others such as the adeno ca of vagina was seen after 20 yrs..d\/t DES for threatened abortion<\/li><\/ul>\n\n\n\n
Factors affecting drug use in Pregnancy<\/strong><\/p>\n\n\n\n
- Maternal Factors<\/strong>
- Physiological Changes<\/li><\/ol><\/li>
- Cardiovascular System<\/strong><\/li><\/ol>\n\n\n\n
Plasma Volume – \u2191ses by 40-45%<\/p>\n\n\n\n
Heart rate and stroke volume increase in pregnancy leading to a 30\u201350% increase in maternal cardiac output (CO)<\/p>\n\n\n\n
Serum albumin concentration lowered<\/p>\n\n\n\n
- Renal System<\/strong><\/li><\/ul>\n\n\n\n
GFR \u2191ses by 25% in 2nd<\/sup> wk to 50 % by 2nd<\/sup> trimester<\/p>\n\n\n\n
Renal plasma flow \u2191ses by approx. 80%<\/p>\n\n\n\n
hypervolemia-induced hemodilution lowers the protein concentration.<\/p>\n\n\n\n
- Gastrointestinal System<\/strong><\/li><\/ul>\n\n\n\n
Reflux of gastric secretions, Due to altered stomach position and decreased lower esophageal sphincter tone.<\/p>\n\n\n\n
Nausea\/Vomiting<\/p>\n\n\n\n
- Pharmacokinetic Changes
- Absorption
- Gastric acid production is decreased during pregnancy, whereas mucus secretion is increased \u00e0 Increase in gastric pH.<\/strong>
- These changes can increase ionization of weak acids<\/strong> (e.g., aspirin) and reduce their absorption<\/strong>, and weak bases (e.g., caffeine) will diffuse more readily since they will be primarily unionized.<\/li><\/ul>
- Drug drug interaction becomes important as antacids and iron may chelate co-administered drugs, which further decreases their already reduced absorption<\/li><\/ul>
- Therefore, oral medications should be administered when nausea is minimal.<\/li><\/ul><\/li><\/ul>
- Nausea and vomiting in early pregnancy \u00e0 decrease the absorption following oral administration.<\/li><\/ul>
- GI transit time is prolonged<\/strong>.<\/li><\/ul><\/li><\/ul>
- Distribution
- 40- 45% increase in plasma <\/strong>\u00e0<\/strong> increased volume of distribution<\/strong> for hydrophilic drugs.<\/li><\/ul>
- Body fat expands by approximately 4 kg \u00e0 increasing the volume of distribution for lipophilic drugs.<\/strong><\/li><\/ul>
- Reduced concentrations of albumin and alpha 1-acid glycoprotein\u00e0 Decreased protein binding and favors more distribution to tissues.<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n\n
ENZYME<\/strong><\/td> PREGNANCY INDUCED CHANGE<\/strong><\/td> POTENTIAL SUBSTRATES IN OBSTETRICS<\/strong><\/td><\/tr> CYP3A4<\/td> Increased<\/td> Nifedipine, and indinavir<\/td><\/tr> CYP2D6<\/td> Increased<\/td> Metoprolol,dextromethorphan, paroxetine,duloxetine, fluoxetine, citalopram<\/td><\/tr> CYP2C9<\/td> Increased<\/td> NSAIDs,phenytoin,and fluoxetine<\/td><\/tr> CYP2C19<\/td> Decreased<\/td> Citalopram, diazepam, omeprazole, pantoprazole, propranolol<\/td><\/tr> CYP1A2<\/td> Decreased<\/td> Theophylline, clozapine, olanzapine, ondansetron<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n - Elimination
- GFR is 50% higher by the 2nd trimester and continues to increase until the last week of pregnancy.<\/li><\/ol>
- If a drug is solely excreted by glomerular filtration, its renal clearance is expected to parallel changes in GFR. <\/li><\/ol>
- For example, the clearance of lithium, which used to treat bipolar disorder, is doubled during the third trimester of pregnancy compared with the non- pregnant state, leading to sub-therapeutic drug concentrations<\/li><\/ol>
- Placental factors
- Surface area and thickness of placenta<\/li><\/ol>
- Placental blood flow<\/li><\/ol>
- Biotransformation reactions in placenta<\/li><\/ol>
- Transporters in placenta<\/li><\/ol><\/li><\/ol><\/li><\/ol>\n\n\n\n
placental drug metabolism remains virtually unexplored. Much of the available” data is of a preliminary, exploratory nature and much is also conflicting. It has become evident, however, that in comparison with the liver, the placenta possesses a very limited capacity to biotransform foreign organic molecules.<\/p>\n\n\n\n
Three types of drug transfer across the placenta are recognized:<\/p>\n\n\n\n
- Complete transfer (type 1 drugs): for example, thiopental<\/li><\/ol>\n\n\n\n
\u2003Drugs exhibiting this type of transfer will rapidly cross the placenta with pharmacologically significant concentrations equilibrating in maternal and fetal blood.<\/p>\n\n\n\n
- Exceeding transfer (type 2 drugs): for example, ketamine<\/li><\/ul>\n\n\n\n
\u2003These drugs cross the placenta to reach greater concentrations in fetal compared with maternal blood.<\/p>\n\n\n\n
- Incomplete transfer (type 3 drugs): for example, succinylcholine<\/li><\/ul>\n\n\n\n
\u2003These drugs are unable to cross the placenta completely, resulting in higher concentrations in maternal compared with fetal blood.<\/p>\n\n\n\n
Properties that Influence Medications Crossing the Placenta<\/strong><\/p>\n\n\n\n
\u2022 Molecular weight<\/p>\n\n\n\n
\u2022 Degree of protein binding<\/p>\n\n\n\n
\u2022 Degree of ionization (pKa)<\/p>\n\n\n\n
\u2022 Lipid solubility<\/p>\n\n\n\n
\u2022 pH of maternal blood influences the degree of ionization<\/p>\n\n\n\n
\u2022 Fetal to maternal concentration gradient<\/p>\n\n\n\n
- Awareness about drug use
- Awareness about the harm drugs can cause to the mother as well as baby<\/li><\/ul>
- Education of women to avoid self-medication if they suspect pregnancy<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Nutritional Status
- Nutritional requirements are increased in pregnancy<\/li><\/ul>
- Deficiency or excess of nutrients affect expression of genes \u00e0 may enhance harmful effects of drugs<\/li><\/ul>
- Excess of Vit. D is harmful by itself \u00e0 hypercalcemia & supravalvular aortic stenosis.<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Fetal Factors
- Drugs given to mother at parturition may affect neonate<\/li><\/ul>
- Sulphonamides are highly protein bound compete with bilirubin for albumin binding sites, exacerbating neonatal jaundice<\/li><\/ul>
- Conjugation capacity of fetal liver is low \u00e0 Low concentration of UDP glucuronic acid and glucuronyl transferase<\/li><\/ul>
- Metabolic & excretory capacity is immature leading to problems with elimination (Near anticipation of delivery)<\/li><\/ul>
- Variation in genetic susceptibility to drugs<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Drug Related Factors<\/strong>
- Factors governing drug transfer across placenta<\/li><\/ul>
- Dose of drug<\/li><\/ul>
- Timing of exposure
- ACE inhibitors Exposure in the 2nd and 3rd trimester of pregnancy is associated with fetal hypotension, renal tubular dysplasia, anuria-oligohydramnios, growth restriction, hypocalvaria, and death<\/li><\/ul><\/li><\/ul>
- Past treatment history
- Anti-hypertensives<\/li><\/ul>
- Oral hypoglycaemics<\/li><\/ul>
- Antiepileptics<\/li><\/ul>
- Anticoagulants<\/li><\/ul>
- Miscellaneous \u2013 Isotretinoin<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n\n
![\"\"](\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-404.png?w=480\")
<\/figure>\n\n\n\nDrug Labeling<\/strong><\/p>\n\n\n\n
- \u201cPregnancy\u201d and \u201cLactation\u201d sections will include these subheadings:
- Pregnancy exposure registries<\/li><\/ul>
- Risk summary<\/li><\/ul>
- Clinical considerations<\/li><\/ul>
- Data<\/li><\/ul><\/li>
- Provide more detailed information regarding human and animal data of the drug and specific adverse reactions.<\/li><\/ul>\n\n\n\n
Pregnancy exposure registries<\/strong><\/p>\n\n\n\n
FDA does not conduct any studies collected in the pregnancy exposure registries and does not endorse any registry; however, the agency may recommend or require that a drug company implement a pregnancy exposure registry based on certain criteria.<\/p>\n\n\n\n
TERIS<\/strong><\/p>\n\n\n\n
- Teratogen Information System<\/li>
- Online database<\/li>
- Based on thorough review of published clinical and experimental literature.<\/li>
- Consists of categories such as \u2013<\/li><\/ul>\n\n\n\n
- Unlikely, none or minimal risk – Nifedipine<\/li>
- Small to moderate – Lamotrigine<\/li>
- Moderate to high risk \u2013 Methotrexate, Phenytoin<\/li>
- Risk undetermined.<\/li><\/ol>\n\n\n\n
![\"\"](\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-405.png?w=480\")
<\/figure>\n\n\n\n![\"\"](\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-406.png?w=480\")
<\/figure>\n","protected":false},"excerpt":{"rendered":"Drug use in Pregnancy Thalidomide \u00e0 1957 as an over-the-counter remedy, based on the maker\u2019s safety claims. Australian obstetrician Dr. William McBride discovered that the drug also alleviated morning sickness. He started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend. In 1961, McBride began to associate this so-called[…]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/889"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=889"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/889\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=889"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=889"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=889"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
- Clinical considerations<\/li><\/ul>
- Risk summary<\/li><\/ul>
- Pregnancy exposure registries<\/li><\/ul>
- \u201cPregnancy\u201d and \u201cLactation\u201d sections will include these subheadings:
- Miscellaneous \u2013 Isotretinoin<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n\n
- Anticoagulants<\/li><\/ul>
- Antiepileptics<\/li><\/ul>
- Oral hypoglycaemics<\/li><\/ul>
- Anti-hypertensives<\/li><\/ul>
- Past treatment history
- ACE inhibitors Exposure in the 2nd and 3rd trimester of pregnancy is associated with fetal hypotension, renal tubular dysplasia, anuria-oligohydramnios, growth restriction, hypocalvaria, and death<\/li><\/ul><\/li><\/ul>
- Timing of exposure
- Dose of drug<\/li><\/ul>
- Factors governing drug transfer across placenta<\/li><\/ul>
- Drug Related Factors<\/strong>
- Variation in genetic susceptibility to drugs<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Metabolic & excretory capacity is immature leading to problems with elimination (Near anticipation of delivery)<\/li><\/ul>
- Conjugation capacity of fetal liver is low \u00e0 Low concentration of UDP glucuronic acid and glucuronyl transferase<\/li><\/ul>
- Sulphonamides are highly protein bound compete with bilirubin for albumin binding sites, exacerbating neonatal jaundice<\/li><\/ul>
- Drugs given to mother at parturition may affect neonate<\/li><\/ul>
- Fetal Factors
- Excess of Vit. D is harmful by itself \u00e0 hypercalcemia & supravalvular aortic stenosis.<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Deficiency or excess of nutrients affect expression of genes \u00e0 may enhance harmful effects of drugs<\/li><\/ul>
- Nutritional requirements are increased in pregnancy<\/li><\/ul>
- Nutritional Status
- Education of women to avoid self-medication if they suspect pregnancy<\/li><\/ul><\/li><\/ul>\n\n\n\n
- Awareness about the harm drugs can cause to the mother as well as baby<\/li><\/ul>
- Awareness about drug use
- Incomplete transfer (type 3 drugs): for example, succinylcholine<\/li><\/ul>\n\n\n\n
- Exceeding transfer (type 2 drugs): for example, ketamine<\/li><\/ul>\n\n\n\n
- Complete transfer (type 1 drugs): for example, thiopental<\/li><\/ol>\n\n\n\n
- Transporters in placenta<\/li><\/ol><\/li><\/ol><\/li><\/ol>\n\n\n\n
- Biotransformation reactions in placenta<\/li><\/ol>
- Placental blood flow<\/li><\/ol>
- Surface area and thickness of placenta<\/li><\/ol>
- Placental factors
- For example, the clearance of lithium, which used to treat bipolar disorder, is doubled during the third trimester of pregnancy compared with the non- pregnant state, leading to sub-therapeutic drug concentrations<\/li><\/ol>
- If a drug is solely excreted by glomerular filtration, its renal clearance is expected to parallel changes in GFR. <\/li><\/ol>
- GFR is 50% higher by the 2nd trimester and continues to increase until the last week of pregnancy.<\/li><\/ol>
- Elimination
- Reduced concentrations of albumin and alpha 1-acid glycoprotein\u00e0 Decreased protein binding and favors more distribution to tissues.<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n\n
- Body fat expands by approximately 4 kg \u00e0 increasing the volume of distribution for lipophilic drugs.<\/strong><\/li><\/ul>
- 40- 45% increase in plasma <\/strong>\u00e0<\/strong> increased volume of distribution<\/strong> for hydrophilic drugs.<\/li><\/ul>
- Distribution
- GI transit time is prolonged<\/strong>.<\/li><\/ul><\/li><\/ul>
- Nausea and vomiting in early pregnancy \u00e0 decrease the absorption following oral administration.<\/li><\/ul>
- Therefore, oral medications should be administered when nausea is minimal.<\/li><\/ul><\/li><\/ul>
- Drug drug interaction becomes important as antacids and iron may chelate co-administered drugs, which further decreases their already reduced absorption<\/li><\/ul>
- These changes can increase ionization of weak acids<\/strong> (e.g., aspirin) and reduce their absorption<\/strong>, and weak bases (e.g., caffeine) will diffuse more readily since they will be primarily unionized.<\/li><\/ul>
- Gastric acid production is decreased during pregnancy, whereas mucus secretion is increased \u00e0 Increase in gastric pH.<\/strong>
- Absorption
- Pharmacokinetic Changes
- Gastrointestinal System<\/strong><\/li><\/ul>\n\n\n\n
- Renal System<\/strong><\/li><\/ul>\n\n\n\n
- Maternal Factors<\/strong>