Principles of Drug Therapy in Pregnancy

  • Gary C. Cupit
  • Heschi H. Rotmensch

Abstract

The past several decades have witnessed major advances in the practice of therapeutics. It is now recognized that the nature, duration, and intensity of drug action are dependent not only on the intrinsic properties of the drug but also on the interaction with the host to whom the drug is being administered. Although research has been proceeding at a rapid rate in adult medicine, developments in drug therapy during pregnancy, the perinatal period, and in the neonate are lagging far behind the other disciplines. This is because research in humans during pregnancy is limited by ethical and practical considerations. Therefore, present drug use in pregnancy is based on cautious empiricism, with therapeutic misadventures acting as warning signals.

Keywords

Nicotine Warfarin Levodopa Propranolol Lidocaine 

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References

  1. 1.
    Wood AJJ, Carr K, Vestal RE, et al: Direct measurement of the propranolol bioavailability during accumulation to steady-state. Br J Clin Pharmacol 6: 345–350, 1978PubMedGoogle Scholar
  2. 2.
    Huet M, LeLorier J, Pomier G, et al: Bioavailability of lidocaine in normal volunteers and cirrhotics. Gastroenterology 75: 968A, 1978Google Scholar
  3. 3.
    Hill N, Antman EM, Green LH, et al: Intravenous nitroglycerin—a review of pharmacology, indications, therapeutic effects and complications. Chest 79: 69–76, 1981PubMedCrossRefGoogle Scholar
  4. 4.
    Kostenbauder HB, Rapp RP, McGovern JP, et al: Bioavailability and single-dose pharmacokinetics of intramuscular phenytoin. Clin Pharmacol Ther 18: 449–456, 1975PubMedGoogle Scholar
  5. 5.
    Wilder BJ, Serrano EE, Ramsey E, et al: A method of shifting from oral to intramuscular diphenylhydantoin administration. Clin Pharmacol Ther 16: 507–513, 1974PubMedGoogle Scholar
  6. 6.
    Davison JS, Davison MC, Hay DM: Gastric emptying time in late pregnancy and labour. J Obstet Gynaecol Br Commonw 77: 37–41, 1970PubMedCrossRefGoogle Scholar
  7. 7.
    Gryboski WA, Spiro HM: The effect of pregnancy on gastric secretion. N Engl J Med 255: 1131–1134, 1956PubMedCrossRefGoogle Scholar
  8. 8.
    Krauer B, Krauer F: Drug kinetics in pregnancy. Clin Pharmacokinet 2: 167–181, 1977PubMedCrossRefGoogle Scholar
  9. 9.
    Pirani BKK, Campbell DM, MacGillivray I: Plasma volume in normal pregnancy. J Obstet Gynaecol Br Commonw 80: 884–887, 1973PubMedCrossRefGoogle Scholar
  10. 10.
    Katz R, Karliner JS, Resnik R: Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects. Circulation 58: 434–441, 1978PubMedGoogle Scholar
  11. 11.
    Munnell EW, Taylor HC: Liver blood flow in pregnancy hepatic vein catheterization. J Clin Invest 26: 952–956, 1947CrossRefGoogle Scholar
  12. 12.
    Krauer B, Krauer F, Hytten FE: Drug disposition and pharmacokinetics in the maternal-placental-fetal unit. Pharmacol Ther 10: 301–328, 1980PubMedCrossRefGoogle Scholar
  13. 13.
    Appel GB, Neu HC: Gentamicin in 1978. Ann Intern Med 89: 528–538, 1978PubMedGoogle Scholar
  14. 14.
    Aronson JK: Clinical pharmacokinetics of digoxin 1980. Clin Pharmacokinet 5: 137–149, 1980PubMedCrossRefGoogle Scholar
  15. 15.
    Robertson EG: Physiologic adjustments in pregnancy: Water metabolism. Clin Obstet Gynecol 2: 431–440, 1975Google Scholar
  16. 16.
    Perucca E, Crema A: Plasma protein binding of drugs in pregnancy. Clin Pharmacokinet 7: 336–352, 1982PubMedCrossRefGoogle Scholar
  17. 17.
    Reboud P, Groulade J, Groslambert P, et al: The influence of normal pregnancy and the postpartum state of plasma proteins and lipids. Am J Obstet Gynecol 86: 820–828, 1963PubMedGoogle Scholar
  18. 18.
    Wood M, Wood AJJ: Changes in plasma drug binding and α1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther 29: 522–526, 1981PubMedCrossRefGoogle Scholar
  19. 19.
    Perucca E, Ruprah M, Richens A: Decreased serum protein binding of diazepam and valproic acid in pregnant women. Br J Clin Pharmacol 12: 276P, 1981Google Scholar
  20. 20.
    Chen SS, Perucca E, Lee JN, et al: Serum protein binding and free concentration of phenytoin and phenobarbitone in pregnancy. Br J Clin Pharmacol 13: 547–552, 1982PubMedGoogle Scholar
  21. 21.
    Dean M, Stock B, Patterson RJ, et al: Serum protein binding of drugs during and after pregnancy in humans. Clin Pharmacol Ther 28: 253–261, 1980PubMedCrossRefGoogle Scholar
  22. 22.
    Dvorchik BH: Drug disposition during pregnancy. Biol Res Preg 3: 129–137, 1982Google Scholar
  23. 23.
    Davis M, Simmons GJ, Dordoni B, et al: Induction of hepatic enzymes during normal human pregnancy. J Obstet Gynaecol Br Commonw 81: 690–695, 1973CrossRefGoogle Scholar
  24. 24.
    Davison JM, Hytten FE: Glomerular filtration during and after pregnancy. J Obstet Gynaecol Br Commonw 81: 588–595, 1974PubMedCrossRefGoogle Scholar
  25. 25.
    Zaske DE, Cipolle RJ, Strate RG, et al: Rapid gentamicin elimination in obstetric patients. Obstet Gynecol 56: 559–564, 1980PubMedGoogle Scholar
  26. 26.
    Kubacka RT, Johnstone HE, Tan HSI, et al: Intravenous ampicillin pharmacokinetics in the third trimester of pregnancy. Ther Drug Monit 5: 55–60, 1983PubMedCrossRefGoogle Scholar
  27. 27.
    Nau H, Kunz W, Egger HJ, et al: Anticonvulsants during pregnancy and lactation—transplacental, maternal and neonatal pharmacokinetics. Clin Pharmacokinet 7: 508–43, 1982PubMedCrossRefGoogle Scholar
  28. 28.
    Lander CM, Edwards VE, Eadie MJ, et al: Plasma anticonvulsant concentrations during pregnancy. Neurology (Minneap) 27: 128–131, 1977Google Scholar
  29. 29.
    Eadie MJ, Lander CM, Tyrer JH: Plasma drug level monitoring in pregnancy. Clin Pharmacokinet 2: 427–436, 1977PubMedCrossRefGoogle Scholar
  30. 30.
    Peabody JL: Transcutaneous oxygen measurement to evaluate drug effects. Clin Perinato16: 109–121, 1979Google Scholar
  31. 31.
    Juchau MR, Chao ST, Omiecinski CJ: Drug metabolism by the human fetus. Clin Pharmacokinet 5: 320–339, 1980PubMedCrossRefGoogle Scholar
  32. 32.
    National Foundation-“March of Dimes”: Facts. White Plains, New York, 1979Google Scholar
  33. 33.
    Wilson JG: Embryotoxicity of drugs in man, in Wilson JG, Fraser FC (eds): Handbook of Teratology, vol 1. New York, Plenum Press, 1977, p 309Google Scholar
  34. 34.
    Bleyer WA, Au WYW, Lang WA, et al: Studies on the detection of adverse drug reactions in the newborn. I. Fetal exposure to maternal medication. JAMA 213: 2046–2050, 1970PubMedCrossRefGoogle Scholar
  35. 35.
    Yager JW: Congenital malformations and environmental influence: The occupational environment of the laboratory worker. J Occup Med 15: 724–728, 1973PubMedGoogle Scholar
  36. 36.
    Stern L: In vivo assessment of the teratogenic potential of drugs in humans. Obstet Gynecol 58: 3S–8S, 1981PubMedGoogle Scholar
  37. 37.
    Ballard PL, Ballard RA: Corticosteroids and respiratory distress syndrome: Status 1979, Pediatrics 63: 163–165, 1979PubMedGoogle Scholar
  38. 38.
    Petersen MC, Nation RL, Ashley JJ, et al: The placental transfer of betamethasone. Eur J Clin Pharmacol 18: 245–254, 1980PubMedCrossRefGoogle Scholar
  39. 39.
    Harrigan JT, Kangos JJ, Sikka A, et al: Successful treatment of fetal congestive heart failure secondary to tachycardia. N Engl J Med 304: 1527–1529, 1981PubMedCrossRefGoogle Scholar
  40. 40.
    Newburger JW, Keane JF: Intrauterine supraventricular tachycardia. J Pediatr 95: 780–786, 1979PubMedCrossRefGoogle Scholar
  41. 41.
    Kerenyi TD, Gleicher N, Meller J, et al: Transplacental cardioversion in intrauterine supraventricular tachycardia and digitalis. Lancet 2: 393–395, 1980PubMedCrossRefGoogle Scholar
  42. 42.
    Klein AM, Holzman IA, Austin EM: Fetal tachycardia prior to the development of hydrops. Attempted pharmacologic cardioversion: case report. Am J Obstet Gynecol 134: 347–348, 1979PubMedGoogle Scholar
  43. 43.
    Dumesic DA, Silverman NH, Tobias S, et al: Transplacental cardioversion of fetal supraventricular tachycardia with procainamide. N Engl J Med 307: 1128–1131, 1982PubMedCrossRefGoogle Scholar
  44. 44.
    Gladstone GR, Hordorf A, Gersony WM: Propranolol administration during pregnancy: Effects on the fetus. J Pediatr 86: 962–964, 1975PubMedCrossRefGoogle Scholar
  45. 45.
    Habib A, McCarthy JS: Effects on the neonate of propranolol administered during pregnancy. J Pediatr 91: 808–811, 1977PubMedCrossRefGoogle Scholar
  46. 46.
    Bray RE, Boe RW, Johnson WL: Transfer of ampicillin into the fetus and amniotic fluid from maternal plasma in late pregnancy. Am J Obstet Gynecol 96: 938–942, 1966PubMedGoogle Scholar
  47. 47.
    Depp RC, Kind AC, Kirby WMM, et al: Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid. Am J Obstet Gynecol 107: 1054–1057, 970Google Scholar
  48. 48.
    Szeto HH, Mann LI, Ghaktharathsalan A, et al: Meperedine pharmacokinetics in the maternal-fetal unit. J Pharmacol Exp Ther 206: 448–459, 1978PubMedGoogle Scholar
  49. 49.
    Idanpaan-Heikkala JE, Jouppila JE, Poulakka, et al: Placental transfer and fetal metabolism of diazepam in early human pregnancy. Am J Obstet Gynecol 109: 1011–1061, 1971Google Scholar
  50. 50.
    Abramovich DR, Wade DP: Transplacental passage of steroids: The presence of corticosteroids in amniotic fluid. J Obstet Gynecol Br Commonw 76: 610–614, 1969CrossRefGoogle Scholar
  51. 51.
    Anderson ABM, Gennser G, Jeremy JY, et al: Placental transfer and metabolism of betamethasone in human pregnancy. Obstet Gynecol 49: 471–474, 1977PubMedGoogle Scholar
  52. 52.
    Fouron JC: Dynamics of the placental transfer of digoxin in the dog. Biol Neonate 23: 116–122, 1973PubMedCrossRefGoogle Scholar
  53. 53.
    Carrier G, Hume AS, Douglas BH, et al: Disposition of barbiturates in the maternal blood, fetal blood and amniotic fluid. Am J Obstet Gynecol 105: 1069–1071, 1969PubMedGoogle Scholar
  54. 54.
    Basso A, Fernandez A, Olthade O, et al: Passage of mannitol from mother to amniotic fluid to fetus. Obstet Gynecol 49: 628–631, 1977PubMedGoogle Scholar
  55. 55.
    Sack J, Fischer DA, Lam RW: Thyroid hormone metabolism in amniotic and allantoic fluids of the sheep. Pediatr Res 9: 837–841, 1975PubMedGoogle Scholar
  56. 56.
    Seeds AE: Current concepts of amniotic fluid dynamics. Am J Obstet Gynecol 138: 575–586, 1980PubMedGoogle Scholar
  57. 57.
    Duenhoeffer JH, Pritchard JA: Fetal respiration: Quantitative measurements of amniotic fluid inspired near term by human and rhesus fetuses. Am J Obstet Gynecol 125: 306–309, 1976Google Scholar
  58. 58.
    Shier RW, Sprague AD, Dilts PV: Placental transfer of meperidine HCI. Part II. Am J Obstet Gynecol 115: 556–559, 1973PubMedGoogle Scholar
  59. 59.
    Seeds AE: Basic concepts of maternal-fetal amniotic fluid exchange—their relevance to fetal therapeutics. Pediatr Clin North Am 28: 231–240, 1981PubMedGoogle Scholar
  60. 60.
    Shoeman DW, Kaufman RE, Azarnoff DL, et al: Placental transfer of diphenylhydantoin in the goat. Biochem Pharmacol 21: 1237–1244, 1972PubMedCrossRefGoogle Scholar
  61. 61.
    Lien EJ, Kuwahara J, Koda RT: Diffusion of drugs into prostatic fluid and milk. Drug Intell Clin Pharm 8: 470–475, 1974Google Scholar
  62. 62.
    Catz CS, Giacoia GP: Drugs in breast milk. Pediatr Clin North Am 19: 151–166, 1972PubMedGoogle Scholar
  63. 63.
    Vorheer H: Drug excretion in breast milk. Postgrad Med 56: 97–104, 1974Google Scholar
  64. 64.
    Dickey RP: Drugs affecting lactation. Semin Perinatol 3: 279–286, 1979PubMedGoogle Scholar
  65. 65.
    Sousa PLR: Reestablishment of lactation with metoclopramide. J Trop Pediatr 21: 214–216, 1975Google Scholar
  66. 66.
    Briggs CG, Bodendorfer TW, Freeman RK, et al: Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Baltimore, London, Williams & Wilkins, 1983Google Scholar
  67. 67.
    Barr WH: Principles of biopharmaceutics. Am J Pharm Educ 52: 958–981, 1968Google Scholar
  68. 68.
    Richens AL, Dunlop A: Serum-phenytoin levels in the management of epilepsy. Lancet 2: 247–248, 1975PubMedCrossRefGoogle Scholar
  69. 69.
    Swintosky JV: Illustrations and pharmaceutical interpretations of first order drug elimination rate from the bloodstream. J Am Pharm Assoc Sci Ed 45: 395–400, 1956CrossRefGoogle Scholar
  70. 70.
    Berkow R (ed): Merck Manual, ed 14. Rahway, Merck Sharp and Dohme Research Laboratories, 1982, p 2255Google Scholar

Copyright information

© Plenum Press Publishing Corporation 1985

Authors and Affiliations

  • Gary C. Cupit
  • Heschi H. Rotmensch

There are no affiliations available

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