Drugs in Pregnancy and Lactation - Pharmacology

UNIVERSITAS LAMPUNG DRUGS IN PREGNANCY AND LACTATION MAYA GANDA RATNA PHARMACOLOGY DEPARTMENT FACULTY OF MEDICINE SEPTEMBER 2024  Thalidomide Tragedy (1961-1962) Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant wome...

UNIVERSITAS LAMPUNG DRUGS IN PREGNANCY AND LACTATION MAYA GANDA RATNA PHARMACOLOGY DEPARTMENT FACULTY OF MEDICINE SEPTEMBER 2024  Thalidomide Tragedy (1961-1962) Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant women. Pregnant woman should use drug or drugs due to: Suffer from acute illness Suffer from chronic disease during pregnancy Complication during pregnancy Physiological changes caused by Complication in her pregnancy labour Maternal Pharmacokinetic Changes in Pregnancy Absorption Delayed gastric emptying Nausea and vomiting Gastric pH is increased Distribution Maternal plasma volume increases Body fat increases Plasma albumin concentration decreases Steroids and hormones compete in protein binding Maternal Pharmacokinetic Changes in Pregnancy Metabolism Hepatic perfusion increases Activity of metabolic enzymes and drug transporters changes Excretion Renal blood flow increases GFR increases by 30%-50% Transplacental Drug Transfer The placenta >> exchange between the mother and fetus for a number of substances, including drugs >> by diffusion Lipid solubility, electrical charge, molecular weight, and degree of protein binding of medications, may influence the rate of transfer across the placenta.  Drug Effects on the Unborn Predictable Unpredictable The known pharmacological Effects that specifically affect the drug properties developing organism and that E.g., masculinization of the cannot be predicted on the basis female fetus by androgenic of the known pharmacological hormones activity profile. Drug Selection During Pregnancy Medication exposure is estimated to account for less than 1% of all birth defects. Factors such as the stage of pregnancy during exposure, medication route of administration, and dose also affect outcomes. Sensitivity of Specific Organs to Teratogenic Agents at Critical Stages of Human Embryogenesis  Drugs and Fetal Anomalies Anticonvulsants Mefenamic acid Fetal hydantoin syndrome Embryotoxic Anticoagulants Aminoglycosides Warfarin syndrome N. VIII, ototoxic, nephrotoxic Alcohol DES Fetal alcohol syndrome Late abnormality  Warfarin syndrome Fetal hydantoin syndrome Paracetamol, penicilline, isoniazide, folic acid Phenothiazine, narcotic analgesics, NSAIDs, antiarrhytmia, diuretics  B1 B2 B3 In animal experiment Data in animal are In animal there is an enhancing there is no enhancing incompletely but there is non in fetal damage, but not surely in fetal damage enhancing in fetal damage in pregnant women E.g., cimethidine, E.g., ticarcylline, E.g., carbamazepine, dypiridamol, amphotericin, dopamine, pyrimethamine, griseofulvin, spectinomycin acethylcysteine, alkaloid trimethoprime, mebendazole belladone Phenitoin, phenobarbitone, valproic acid, clonazepam, quinine, captopril, cytostatic agents, anticoagulants, androgen, steroid anabolics Isotretionine and diethylstilbesterol General Principles of Drug Using in Pregnancy Absolute Correct Appropriate Adjust medication reasons benefits drugs dose Discourage self- Effects on fetus are not always medication as same as on the mother Drugs often Used during Pregnancy Analgesic-antipyretics Antithyroid drugs Antibiotics Hypnotic-sedatives- Antiemetic-antihistaminic psychotropics Antihypertensives Drugs used in asthma Antidiabetics Drug Use During Lactation Drugs present in the maternal organism can be secreted In breast milk and thus be ingested by the infant. Evaluation of risks should be based on factors. In case of doubt, potential danger to the infant can be averted only by weaning.  Drug Use During Lactation Factors influence drug transfer from maternal circulation into breast milk: Degree of protein binding in maternal plasma Molecular weight Lipid solubility (and corresponding fat content of milk) Maternal plasma concentration Drug half-life Drug pH Drug Use During Lactation Infant-related factors: The frequency of feedings and the amount of milk ingested Drugs unstable in gastric acid (aminoglycosides, PPIs, heparin, and insulin) Variability of infants ability to metabolize and excrete ingested medication Transfer of Drugs into Breastmilk Described quantitatively using the milk to plasma (M/P) concentration ratio >1 (isoniazid, sotalol, erithromycin) > administration before the infant’s longest sleep period If the necessary medication is not considered compatible with breastfeeding >> the mother can pump and discard milk Maternal use of topical preparations, nasal sprays, or inhalers Reference