Drug therapy in Pregnancy

Drug therapy in Pregnancy

1. DRUG THERAPY IN PREGNANCY Dr Manjuprasad Moderator : Dr Ravichandra.V 1

2. Overview Introduction Physiological changes during pregnancy Placental transfer of drugs Critical period in fetal development and teratogenesis FDA categories of drug use in pregnancy Commonly used drugs Conclusion 2

3. Introduction More than 50% of pregnant women take prescription or nonprescription (over-the-counter) drugs or use social drugs (such as tobacco and alcohol) or illicit drugs at some time during pregnancy, and use of drugs during pregnancy is increasing . In general, drugs should not be used during pregnancy unless absolutely necessary because many can harm the fetus . About 2 to 3% of all birth defects result from drugs that are taken to treat a disorder or symptom. 3

4. PHYSIOLOGICAL CHANGES DURING PREGNANCY BMR increases by 15-20%, weight gain – 11kg, postural changes GIT changes:- decreased gastric motility & emptying, nausea & vomiting CVS changes:- CO increases by 40%, plasma volume by 45%, low DBP Decreased serum albumin levels Hyper coagulability of blood Increased GFR & renal blood flow 4

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6. PLACENTAL TRANSFER OF DRUGS Rate of transfer of drug across depends on:- Lipid solubility Ionization of drug Molecular size PPB pH difference – [7.0 vs 7.4]- ionic trapping of weak basic drugs - morphine 6

7. Further , placenta is capable of metabolizing drugs Is of little relevance to the mother But has protective effect on fetus Eg :- prednisolone & hydrocortisone are metabolized to inactive compounds ( prednisone, cortisone )- safer for fetus 7

8. Effect of toxic drugs on fetus No effect Little effect Serious fetal toxicity Spontaneous abortion Death Fetal malfunction / malformation 8

9. Harmful effects depend on Nature of drug, dose & its route Stage of pregnancy at which drug is administered Genetic constitution & susceptibility of fetus 9

10. Directly on the fetus - abnormal development [ birth defects or death] Alter the function of the placenta - by constricting blood vessels reducing the blood supply of oxygen and nutrients to the fetus – underweight & underdeveloped baby. Contract uterus:- - reducing the blood supply to fetus -triggering pre-term labor and delivery. 10

11. Gestation may be divided into 4 stages :- Stage of blastocyst formation 0- 16 days A teratogen may either kill embryo by inhibiting cell division If embryo survives exposure to drug – subsequent development normal ALL or NONE phenomena 11

12. Stage of organogenesis 17 – 60 days A teratogen given during this stage – gross structural malformation 12

13. Final stage of histogenesis & maturation Fetus receives adequate supply of nutrients – growth & development Teratogens – deleterious effects on growth & development Eg :- DES – dysplasia , vaginal cancer in the female offspring Exposure to androgens – masculinization of female fetus Short labour delivery stage Drug administered during this phase – risk of neonatal toxicity 13

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15. ‘ terato ’ ; ‘genesis’ Originally used – describe congenital malformation grossly visible at birth & caused by a teratogen Now definition includes ‘structural, biochemical and behavioral abnormalities’ 15

16. A teratogen to be called as teratogen It should result in characteristic set of malformation Exert its effect in particular stage of fetal development Show dose dependent incidence 16

17. HISTORY OF THALIDOMIDE Originally developed in Germany in 1954 Introduced as hypnotic & sedative in 1957 Even recommended in pregnancy as a ‘safe hypnotic’ Teratogenic testing only in mice embryo cells was done In 1961- 1st phocomelia case was reported Drug was withdrawn in 1961 17

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19. FDA CATEGORIES FOR DRUG USE IN PREGNANCY 1979, FDA developed a system determining teratogenic risk of drugs based on animals & human studies Divided drugs into 5 categories Category A Category B Category C Category D Category X 19

20. Category A Drugs in this category have controlled studies in pregnant women that have failed to demonstrate harm to the fetus in the first trimester & have no evidence of further risk in later trimesters. folic acid & vitamin B12 20

21. Category B Animal studies have failed to demonstrate a risk to the fetus and but there are no adequate and well controlled studies in pregnant women acetaminophen, insulin & famotidine 21

22. Category-C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate & well-controlled studies in humans, But potential benefits may warrant use of the drug in pregnant women despite potential risks Pseudoephedrine , fluconazole, ciprofloxacin, fexofenadine, escitalopram , fluoxetine, and bupropion 22

23. Category D There is positive evidence of human fetal risk based on adverse reaction data from controlled studies in pregnant humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks Example: phenytoin. 23

24. Category -X Adequate, well controlled or observational studies have been done in pregnant women or in animals and have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant. warfarin, medroxyprogesterone , estrogens & methotrexate 24

25. DRUGS WITH PROVEN TERATOGENIC EFFECTS PHENYTOIN Fetal hydantoin syndrome Cleft lip, cleft palate & congenital heart disease Vitamin A derivatives:- Isotretinoin , etretinate Significant risk of spontaneous abortion & risk of many significant anomalies 25

26. ACEIs Renal damage – used in 2 nd & 3 rd trimester – oligohydraminos Anomalies of face, limbs & lungs VALPROATE & CARBAMAZEPINE Spina bifida Anencephaly Encephalocele 26

27. WARFARIN Fetal warfarin syndrome Nasal hypoplasia, depressed nasal bridge & hemorrhagic disorders in fetus NSAIDS Premature closure of ductus arteriosus Oligohydraminos 27

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29. DRUGS TERATOGENIC EFFECTS Tetracycline Anomalies of teeth & bone Chloramphenicol Gray Baby Syndrome Sulfonamides Hyperbilirubinemia , Jaundice & Kernicterus Aminoglycosides Ototoxicity Danazol & other Androgenic drugs Masculinization of female fetus DES Vaginal carcinoma in female off springs during teens Oral Hypoglycemic drugs Neonatal Hypoglycemia 29

30. PRECAUTIONS WHILE PRESCRIBING FOR WOMEN OF REPRODUCTIVE AGE Enquire whether she is pregnant / likely to be in near future Advised to avoid conception for certain period of time with certain drugs Isotretinoin – 1 month Mefloquine – 3 months Cytotoxic drugs – 1 year Must be informed to use contraceptive measures when a teratogenic drug is prescribed 30

31. PRECAUTIONS WHILE PRESCRIBING DURING PREGNANCY Treat minor ailments without drugs Doctor must know the safety potential of the drug he prescribes Always prefer drug which has been in market over a longer time than a new drug Make dose adjustment Discourage patient from OTC drug use Centered on benefit verses risk potential [ epilepsy] 31

32. COMMONLY USED DRUGS IN PREGNANCY ANALGESICS & ANTIPYRETICS :- Acetaminophen, phenacetin , aspirin Use of NSAIDs avoided towards end of pregnancy – premature closure of ductus arteriosus ANTIEMETICS :- Antihistaminics – cyclizine , meclizine Ondansetron ANTIBIOTICS:- Beta lactam antibiotics safe 32

33. Nitrofurantoin is safe Erythromycin is safe ; estolate salts are avoided ANTIAMOEBIC DRUGS:- Metronidazole can be used ANTIMALARIALS Chloroquine can be used Rx of acute attacks Quinine – - chloroquine resistant malaria 33

34. ANTI TB DRUGS isoniazid & ethambutol are safe Rifampicin avoided as far as possible due to hepato -toxicity may be used as a 3rd drug Streptomycin is CI – ototoxicity ANTIFUNGAL DRUGS Nystatin & miconazole – safe in pregnancy Ketoconazole - CI 34

35. ANTIASTHMA DRUGS Beta agonists[inhaled], glucocorticoids[inhaled] CARDIAC DRUGS Digoxin & quinidine ANTIHYPERTENSIVES Methyldopa is DOC Labetalol IV for sudden decrease in BP ANTICOAGULANT Heparin 35

36. ANTIHELMINTHES:- Piperazine , pyrantel ANTIEPILEPTICS:- Adequate seizure control necessary for both fetus & mother health Phenytoin, phenobarbiturate , carbamazepine Valproate- CI in pregnancy Here benefits outweighs risk Folic acid supplementation given 36

37. COUGH - codeine, diphenhydramine, dextromethorphan HEART BURN - non systemic antacids CONSTIPATION:- milk of magnesia, glycerin, bisacodyl THYROTOXICOSIS :- Propylthiouracil HYPOTHYROIDISM - Thyroxine Vaccines 37

38. SOCIAL DRUGS IN PREGNANCY Cigarette smoking LBW Defects of heart, brain & face Risk of SIDS, placenta previa , abruptio placenta Risk of PROM, preterm labour, miscarriages & spontaneous abortion 38

39. Alcohol Fetal alcohol syndrome Incidence – 1 in 2000 live birth Facial defects, microcephaly, MR, IUGR, miscarriages Caffeine Found in beverages, soft drinks Evidences suggest that consuming caffeine during pregnancy possess a little/ no risk At high dose – decreases fetal blood flow & iron absorption 39

40. Illicit drugs Cocaine & opiod Serious complication in developing fetus & unborn Constricts blood vessels- reduces blood flow to fetus IUGR, miscarriages, preterm delivery 40

41. CONCERN WITH OTC DRUGS In India due to easy availability of drugs & poor health services Increased proportion of self medication for common complaints Hence consumers always face a threat to unwanted ADRs & drug- drug interations Many OTC drugs are unsafe during pregnancy Women who are / may be / planning to be pregnant must consult a doctor before taking any OTC drug 41

42. CONCLUSION The unique nature of physiology of pregnancy makes treating chronic & acute disorders a challenge As doctors, it is necessary to counsel patients with complete, accurate and current information on the risks and benefits of using medications during pregnancy Prescribe drugs that have been in use over newer alternatives Rx must always be centered on benefit versus risk 42

43. REFERENCES Pharmacological aspects of therapeutics – Goodman and Gilman – 12 th edition Principles of pharmacology Sharma and Sharma 2 nd edition Rang & Dale 7 th edition Textbook of medical pharmacology – Dr.Padmaja Udaykumar – fourth edition Pharmacology & pharmacotherapeutics – R.S. Satoskar , S.D.Bhandarkar , Nirmala.N.Rege http:// www.merckmanuals.com/home/womens_health_issues/drug_use_during_pregnancy/drug_use_during_pregnancy.html Basic and clinical pharmacology – Katzung 13 th edition Journals from web 43

44. THANK YOU 44