Drugs Used In Pregnancy And Lactation PDF

Drugs used in Pregnancy and Lactation Presented by: Dr Mohammad Jaffar Department of Pharmacology, BMC, Jeddah Gastro - esophageal reflux: Antacids that have a low sodium and NO aluminum content may be recommended. Omeprazole – a tablet you take once a day [With caution] Constipation: Increase...

Drugs used in Pregnancy and Lactation Presented by: Dr Mohammad Jaffar Department of Pharmacology, BMC, Jeddah Gastro - esophageal reflux: Antacids that have a low sodium and NO aluminum content may be recommended. Omeprazole – a tablet you take once a day [With caution] Constipation: Increase fiber intake, Keep well hydrated and Exercise Recommend use of bulk-forming laxatives as first-line treatment. Ex: Ispaghula An osmotic laxative may be considered. Ex: Lactulose, sorbitol Stimulant laxatives should be used if a stimulant effect is necessary. Ex: Magnesium salts Nausea and vomiting: Usually starts before 9 weeks of pregnancy. For most women, it goes away by the second trimester (14 weeks of pregnancy) Recommendation: Vitamin B6 recommended as first-line treatment. Doxylamine (first-generation antihistamine) can be added to vitamin B6 ,the combination reduces symptoms by 70%. Hemorrhoids: May worsen during pregnancy Recommendation: Avoid straining at stool Astringents are preferred. Use topical anesthetics and corticosteroids with caution. Common cold: Avoid use of drugs: they are not curative* Avoid use of combination drugs Prefer topical rather than systemic administration of decongestant nasal sprays/drops, containing phenylephrine, oxymetazoline, or tramazoline are preferred in pregnancy and breastfeeding because they act locally and very little is absorbed into the bloodstream. The use of saline nasal drops is recommended. Headache and back pain: Common complaints in pregnancy Analgesic of choice: paracetamol.  Epilepsy in pregnancy Anti-Epileptics in pregnancy is associated with an increased risk of congenital malformations including a higher risk of neural tube defects. Dose adjustments of antiepileptic agents are required throughout pregnancy. Single antiepileptic therapy is preferred over multiple therapy. folic acid supplementation should be given during the planning stage and continued during the pregnancy. After birth, the neonate is at risk of developing antiepileptic-associated neonatal hemorrhage. This is counteracted by the administration of vitamin K injection at birth.* It has to be explained to the mother that compliance to antiepileptic drug therapy is essential for the well-being of fetus and mother.  Taking the recommended 400 micrograms (mcg) of folic acid (vitamin B9) before and during normal pregnancy can help prevent birth defects of the baby's brain, spinal cord and autistic traits. Lamotrigine and levetiracetam are considered safer in pregnancy It is not suggested to advocate high dose folic acid supplementation in women with epilepsy (NOT clear yet).*  Diabetes Blood glucose control is essential during pregnancy and benefits of antidiabetic treatment overrule the risks of therapy. Insulin is the drug of choice during pregnancy. Sulphonylurea are relatively contraindicated during pregnancy (occurrence of neonatal hypoglycemia reported). Metformin has a very low risk of birth defects and complications for the baby, making this drug safe to take before and during pregnancy. Metformin is also safe to take while breastfeeding*  Anti-infective agents Avoid use of co-trimoxazole, tetracyclines, griseofulvin, itraconazole and ketoconazole Recommended drugs: amoxicillin, erythromycin Analgesics NSAIDs may cause delayed onset and increase duration of labor if taken during the third trimester. Recommended drug: paracetamol, NSAIDs topical formulations are suitable. COX-2 inhibitors: to be avoided, no clinical data Non-selective COX inhibitors: short-acting agents that do not have an active metabolite are preferred (e.g. Diclofenac).*  Vitamins During lactation there is increased requirements for some vitamins and minerals (Folate, vitamin B2, B6, B12, C); Avoid use of megadose regimens. Immunization and pregnancy The use of immunizing agents during pregnancy should be limited. Consider the use of tetanus toxoids (in case of accidents) and influenza vaccines according to the individual case. Rubella vaccination should be promoted to women planning a pregnancy.  Diet and pregnancy Pregnant women should be advised on a healthy balanced diet where calorie intake is increased during the pregnancy. Food intake should include foods rich in calcium and vitamin D (dairy products), iron (lean red meat) and folate (green vegetables). Should avoid excessive amounts of vitamin A: Teratogenic in excessive amounts* Foods rich in iron must be consumed Vitamin C supplementation (citrus fruit) improves absorption of iron.  Mutagenicity vs. Teratogenicity What are the differences between mutagenicity and teratogenicity Mutagenesis is the ability of chemicals to cause changes in the genetic materials in the nucleus, either egg or sperm Teratogenicity is the ability of chemicals to cause birth defects in the fetus after zygote formation  Basing up on the side effects produced by the drugs; the drugs are categorized in to different categories: Category-A (safe) Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in late trimesters II & III), Possibility of fetal harm appears remote. E.g. Replacement dose of thyroid hormones Category-B Animal studies showed no harm to fetus But, no adequate and well-controlled studies in pregnant women, or animal studies have shown an adverse effect or to demonstrate a risk to the fetus  Category-C Either studies in animals have revealed adverse effects on the fetus (teratogenic) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to fetus Category-D There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). E.g. ACE inhibitors.  Category-X (definite human teratogenic risk) Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. Drug is contraindicated in women who are or may become pregnant. E.g. thalidomide, retinoids. Anticancer… etc.  Thalidomide The most famous example of teratogenic effects in humans post 1950 occurred after administration of thalidomide to pregnant women a. In testing, thalidomide was considered safe b. The drug was used to relieve nausea, tension, or sleeplessness during pregnancy c. It had been used in German, U.K., Australia, and Japan; very little was used in the U.S. owing to disapproval by the FDA for lack of studies on pregnant animals Observations by a German pediatrician (W. Lenz) and an Australian physician identified thalidomide as being teratogenic b. Unfortunately, ~8000 infants were born between 1959 and 1962 with severe thalidomide- induced malformations, including no arms, no legs, deformed ears, paralyzed faces, and internal malformations  Thalidomide -The thalidomide history raised tremendous concerns about teratogenicity and the need for adequate testing. -The case of thalidomide also illustrates the problem in teratogenicity testing—differential sensitivity among species -The differential response among species suggests an intrinsic genetic susceptibility is operational.  Smoking during pregnancy: Children whose mothers smoked during pregnancy were shown to lag behind non-exposed children in development and were associated with a decreased birth weight. ❖ The effects of smoking on the fetus include: Fetal hypoxia caused by carbon monoxide Intrauterine growth retardation caused by carbon monoxide and nicotine Decreased fetal heart rate and increased blood viscosity Reduced fetal breathing movements Reduced fetal motor movements.  Long-term effects of smoking in children: Both nicotine and cocaine are known to be addictive. Developing fetuses become addicted too. Both drugs constrict blood vessels and decreases oxygen delivery to the increased frequency of bronchitis and pneumonia fetus.  Tetracyclines Yellow-brown discoloration of teeth may occur due to deposition of the antibiotic in calcifying teeth with tetracycline use in late pregnancy. The risk is apparent only after 17 weeks of gestation when the deciduous teeth begin to calcify. Generally, only the deciduous teeth are involved, although with administration of the drug close to term the crowns of the permanent teeth may be stained. Oxytetracycline and Doxycycline are associated with a lower incidence of enamel staining.  Medications for high blood pressure during pregnancy Several medications are available for pregnant women with high blood pressure due to pre- eclampsia. These include: Methyldopa Methyldopa has been studied extensively and is recommended by many experts as the first-line oral antihypertensive medication in pregnancy. Methyldopa can be given in pill form or intravenously in severe cases. Labetalol Labetalol is another first-line oral antihypertensive medication that cause vasodilatation. Labetalol is prescribed in pill form or is given intravenously.  Nifedipine It is a calcium channel blocker. Nifedipine is NOT recommended if the pregnant woman receiving magnesium sulfate therapy. Hydralazine Hydralazine is another drug that can be given orally or intravenously to control hypertension in pregnancy. This drug may be used as an injection in very severe cases of high blood pressure.  Antihypertensives to avoid during pregnancy Angiotensin converting enzyme inhibitors Using these drugs during pregnancy is associated with birth defects such as: fetal hypocephalic head renal defects, anuria, or absence of urine fetal and neonatal death Diuretics Furosemide (Lasix) and hydrochlorothiazide (Microzide) should be avoided during pregnancy. Propranolol It’s been associated with birth defects, such as fetal bradycardia, or slow heartbeat, slowed development, and neonatal hypoglycemia.  Drugs with significant adverse effects on the fetus Drug Trimester Effect Barbiturates ALL Chronic use can lead to neonatal dependence Carbamazepine First Neural tube defects Chlorpropamide ALL Prolonged symptomatic neonatal hypoglycemia Clomipramine Third Neonatal lethargy, hypotonia, cyanosis, hypothermia Cyclophosphamide First Various congenital malformations Diethylstilbestrol All Vaginal adenosis, clear cell vaginal adenocarcinoma Methotrexate First Multiple congenital malformations Metronidazole First May be mutagenic Penicillamine First Cutis laxa (connective tissue disorder), other congenital malformations Phenytoin All Fetal hydantoin syndrome Propylthiouracil All Congenital goiter Streptomycin All Eighth nerve toxicity Smoking All Intrauterine growth retardation; prematurity; sudden infant death syndrome; perinatal complications Tetracycline All Discoloration and defects of teeth and altered bone growth Common drugs excreted in breast milk Drug Effect on Infant Comments Ampicillin Minimal Possible occurrence of diarrhea or allergic sensitization Aspirin Minimal Occasional doses probably safe; high doses may produce significant concentration in breast milk. Caffeine Minimal Caffeine intake in moderation is safe; concentration in breast milk is about 1% of total dose taken by mother. Chloramphenicol Significant Concentrations too low to cause gray baby syndrome; possibility of bone marrow suppression does exist; recommend not taking chloramphenicol while breast-feeding Codeine Minimal Safe in most cases. Diazepam Significant Will cause sedation in breast-fed infants; accumulation can occur in newborns. Digoxin Minimal Insignificant quantities enter breast milk. Iodine (radioactive) Significant Enters milk in quantities sufficient to cause thyroid suppression in infant. Isoniazid (INH) Minimal Milk concentrations equal maternal plasma concentrations. Possibility of pyridoxine deficiency developing in the infant. Oral contraceptives Minimal May suppress lactation in high doses. Propranolol Minimal Very small amounts enter breast milk Propylthiouracil Significant Can suppress thyroid function in infant  Drugs contraindicated during Drugs that may suppress lactation breast feeding – Androgens Bromocriptine – MAO inhibitor Heroin – Ergot derivatives Lithium – Bromocriptine (treatment for hypoprolactinaemia) Phencyclidine – Thiazide diuretics Cocain – Levodopa Cyclosporine – High-dose pyridoxine Ergotamine Thank You