drug use during pregnancy and lactation.pptx

Drug use during pregnancy and lactation

1. Drug use during pregnancy and lactation Haftom G. ( BPharm ., MSc.) Email: [email protected]

2. Drug use during pregnancy and lactation The use of drugs in pregnancy is complicated by the potential for Harmful effects on the growing fetus Altered maternal physiology and Paucity and difficulties of research in this field Note: A ll drugs are assumed as harmful until proven otherwise

3. Drug use during pregnancy and lactation cont’d… Drug use before and during pregnancy lactation requires special consideration Should be avoided or minimized when possible Drug effects on the fetus are often unknown especially with newer drugs Absence of evidence is NOT an evidence of absence During lactation : many drugs are excreted in to the breast milk Hence reach the nursing infant 3

4. Harmful effects on the fetus All drugs are potentially harmful until sufficient data exist to indicate otherwise ‘Social’ drugs (alcohol and cigarette smoking) are definitely damaging and their use must be discouraged . Chat (khat) ??????

5. Placental Barrier Membrane layers separate blood vessels of mother and fetus Not permeable to many lipid-insoluble drugs Provides some protection to the fetus Allows passage of certain non-lipid-soluble drugs Can affect developing embryo or neonate if given to pregnant mother 5

6. Drug Transfer to the Fetus In the placenta, maternal blood is separated from fetal blood by a cellular membrane Drugs can cross the placenta: usually by passive diffusion, but can involve facilitated diffusion and active transport Placental function is also modified by changes in blood flow, and drugs which reduce placental blood flow can reduce birth weight. Human placenta possesses multiple enzymes 6

7. Fig: Placental transfer of drugs from mother to fetus

8. The stage of gestation influences the effects of drugs on the fetus. It is convenient to divide pregnancy into four stages Fertilization and implantation (17 days ) Animal studies suggest that interference with the fetus before 17 days gestation causes abortion, i.e. if pregnancy continues the fetus is unharmed?

9. Organogenesis/embryonic stage (17–57 days) Fetus differentiates to form major organs, critical period for teratogenesis Teratogens : a substance, organism, physical agents or deficiency state capable of inducing abnormal structure or function such as: Gross structural abnormalities Functional deficiencies Intrauterine growth restriction Behavioral aberrations

10. Teratogenic Factors Timing of exposure Developmental stage during exposure Maternal dose and duration Maternal pharmacokinetics Genetic factors/phenotypes Interactions between agents 10

11. Pregnancy Ratings for Drugs Category A No risk to fetus Category B Inconclusive risk in first trimester, no risk in later trimesters Animal studies show that no risk to the fetus but there are no adequate studies in pregnant women or Animal studies show adverse effects but adequate studies in pregnant women have not demonstrated a risk 11

12. Pregnancy ratings f or drugs cont’d…… Category C Give only if potential benefit outweighs risk to fetus Risk is unknown Animal studies show toxicity The drugs have not been adequately studied in humans Category D Evidence of fetal risk: it may be acceptable if life-threatening situation or serious disease Positive evidence of harm to human fetuses 12

13. Pregnancy ratings for drugs cont’d…… Category X Risk outweighs any benefit Studies in animals or humans, or post marketing adverse reaction reports or both, have demonstrated fetal abnormalities

14. Risk category D ACEI eg - captopril , enalapril ARBs eg . Losartan Aminoglycosides , tetracyclines , trimethoprim in third trimester Antiepileptics - eg carbamazepine , phenytoin , valproic acid Antimanic eg lithium Benzodiazepines anti anxiety agents- diazepam, lorazepam , alprazolam NSAIDs eg - ibuprofen, naproxen Opioid analgesics Diuretic and B-blockers- hydrochlorthiazide , propranolol by expert but category B by manufacturer??? 14

15. Risk category X Anticoagulant- warfarin Antineoplastics - cyclophosphamide, Methotrexate Benzodiazepines sedative/hypnotics- e.g flurazepam - Male and female sex hormones Oral contraceptives Statins ( cholestrol lowering agents)- atrovastatin , simvastatin. 15

16. Fetogenic stage Fetus undergoes further development and maturation . Even after organogenesis is almost complete, drugs can still have significant adverse effects on fetal growth and development . ACE inhibitors and angiotensin receptor blockers cause fetal and neonatal renal dysfunction. Drugs used to treat maternal hyperthyroidism can cause fetal and neonatal hypothyroidism. Tetracycline antibiotics inhibit growth of fetal bones and stain teeth.

17. Aminoglycosides cause fetal VIIIth nerve damage. Opioids and cocaine taken regularly during pregnancy can lead to fetal drug dependency. Warfarin can cause fetal intracerebral bleeding . Anticonvulsants may possibly be associated with mental retardation . Cytotoxic drugs can cause intrauterine growth retardation and stillbirth.

18. Delivery Some drugs given late in pregnancy or during delivery may cause particular problems Pethidine : administered as an analgesic can cause fetal apnoea (which is reversed with naloxone) Anaesthetic agents : given during Caesarean section may transiently depress neurological, respiratory and muscular functions. Warfarin : given in late pregnancy causes a haemostasis defect in the baby, and predisposes to cerebral haemorrhage during delivery.

19. Excretion through Mammary Glands Many drugs and their metabolites cross the epithelium of the mammary glands Diffusion: higher maternal plasma levels mean higher breast milk concentrations Excreted in to breast milk Nursing mothers are cautioned against medication use 19

20. Fetal Drug Disposition 60 – 80% passes through liver, the rest travels through ductus venosus to heart and brain Hepatic drug metabolism Adrenal gland metabolism Recirculation through amniotic fluid 20

21. Pharmacokinetics in pregnancy Figure: Pharmacokinetic changes in pregnancy

22. Pharmacokinetics in pregnancy cont’d… Due to physiologic changes during pregnancy Drug effects are less predictable Decreased drug plasma concentration Due to increased plasma volume and body water (about 50% when compared to non- pregnants ) Water soluble drugs will solublize Increased weight and body fat Fat soluble drugs will distribute to fatty tissue: Vol. of distribution & duration of action? 22

23. Drug absorption Gastric emptying and small intestinal motility are reduced. This is of little consequence unless rapid drug action is required. Vomiting associated with pregnancy may make oral drug administration impractical Distribution Blood volume increases by one-third Body water Increases due to a larger extravascular volume and changes in the uterus and breasts.

24. Metabolism Metabolism of drugs by the pregnant liver is increased, largely due to enzyme induction , perhaps by raised hormone levels Liver blood flow does not change Increased rate of elimination of drugs (e.g. theophylline), for which enzyme activity rather than liver blood flow is the main determinant of elimination rate.

25. Pharmacokinetics in pregnancy cont’d… Increased elimination by the kidneys In early pregnancy, due to increased CO Increased excretion of drugs excreted primarily unchanged in the urine e.g penicillins Delayed excretion and prolonged effects of renally excreted drugs In late pregnancy, due to increased size and weight of the uterus Delayed excretion and prolonged effects of renally excreted drugs 25

26. Pediatrics Effects unpredictable in infants Drug doses weight related Higher doses of water-soluble drugs may be needed Less effective blood-brain barrier in infants Slow drug clearance, excretion Longer half-life 26

27. Maternal-placental-fetal circulation Drugs ingested by the pregnant woman reach the fetus through the maternal-placental-fetal circulation Placental transfer begins the fifth week after conception The drug levels are high for the fetus Fetus has low levels of plasma albumin Fetal liver is immature so metabolism occurs slowly Fetal kidney is immature so slow excretion Easily transfer to brain due to poorly developed BBB 27

28. Drug effects on the fetus Any drug that stimulates or depress any system in the mother can affect systems of the fetus Major effect- teratogenesity Drug induced teratogenesity is most likely to occur when drugs are taken during the first trimester of pregnancy. For drugs taken during the second and third trimesters, adverse effects are usually manifested in the neonate(birth to 1 month) and infant(1 month to one year) as growth retardation, respiratory problems, infection or bleeding 28

29. Drug effects on the fetus con’t ….. Drugs taken at any time during pregnancy can affect the baby brain Brain development continues throughout pregnancy and after birth Relatively few therapeutic drugs and many non therapeutic drugs are fetotoxic and teratogenic. Non therapeutic drugs - alcohol, cocaine, heroin, marijuana, metamphetamine and nicotine Caffeine relatively safer but at higher dose (400 mg/day) associated with preterm birth and other complications of pregnancy and should also be avoided. 29

30. Fetal therapeutics Drugs given to mother for therapeutic effects of the fetus Digoxin for fetal tachycardia or heart failure Levothyroxine for hypothyroidism Penicillin for exposure to maternal syphilis Prenatal corticosteroids to promote surfactant production to improve lung function and decrease respiratory distress syndrome in preterm infants 30

31. Maternal therapeutics Anemia Three types of anemia in pregnancy Physiologic anemia- results from expanded blood volume Iron deficiency anemia- long term nutritional deficiency Folic acid deficiency anemia- daily requirement doubles during pregnancy Folic acid supplement is often prescribed But routine use of iron supplement in non-anemic pregnant mothers may lead to excessive levels of Hgb , iron overload, hypertension in the mother and premature birth or low birth weight in the infant. 31

32. Constipation Constipation often occurs during pregnancy probably due to decreased perstalisis increase exercise Fluid intake High fiber foods If not stool softner ( docusate sodium) or saline laxative(milk of magnesia) Avoid mineral oils- Interfere with the absorption of fat soluble vitamins Reduce absorption of vitamin K-bleeding in new born Avoid castor oil, strong laxatives and excessive amounts of any laxative Cause uterine contractions and initiate labour 32

33. Gastroesophageal reflux disease Due to relaxation of esophageal sphincter by hormones and increase abdominal pressure by growing fetus Non pharmacologic- Eat small meals Not eating 2-3 hrs before bed time Avoid caffeine and gas producing foods Sitting in upright position Anti acids H 2 receptor antagonist- ranitidine PPI- esomeprazole 33

34. Gestational diabetes Glucose intolerance found during pregnancy Mild hyperglycemia might be detrimental to the fetus Diet Moderate exercise Insulin: Does not cross placenta Oral antidiabetic drugs have generally been contraindicated Studies show as glyburide is safe Metformin , acarbose and miglitol cause minimal fetal risk 34

35. Nausea and vomiting Occur in early stages of pregnancy Eating small and frequent meals Avoid high fat and high fiber foods Drugs: in severe NV only Thalidomide tragedy Some can be used with out apparent teratogenic effect 35

36. Pregnancy induced hypertension Includes preeclampsia and eclampsia Endanger the lives of the mother and the fetus Preeclampsia manifested by hypertension(140/90) and proteinuria >300mg Occur after 20 wks and 6wks postpartum Occur mostly during first pregnancy IV hydralazine or labetalol for BP control Magnesium sulfate for prevention and treatment of seizure If not effectively treated, preeclampsia may progress to ecclampsia , characterized by potentially fatal seizure The only cure is delivery of the baby; CS is needed in some cases 36

37. Thank you