Paediatric Drugs

, Volume 2, Issue 6, pp 419–436 | Cite as

Effects of Antihypertensive Drugs on the Unborn Child

What is Known, and How Should This Influence Prescribing?
  • Shaun M. Khedun
  • Breminand Maharaj
  • Jagidesa Moodley
Review Article

Abstract

This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism.

Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus.

Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (<6 weeks) β-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression.

In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy.

Keywords

Nifedipine Atenolol Antihypertensive Drug Hydralazine Labetalol 

References

  1. 1.
    Robert JM, Redman CWG. Pre-eclampsia more than pregnancy induced hypertension. Lancet 1993; 341: 1447–51CrossRefGoogle Scholar
  2. 2.
    Williams K. Hypertension in pregnancy. Can Fam Physician 1995; 41: 426–32Google Scholar
  3. 3.
    Scott A, Owen O. Recent advances in the aetiology and management of pre-eclampsia. Br J Hosp Med 1996; 55: 476–8PubMedGoogle Scholar
  4. 4.
    Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Carribean. Br J Obstet Gynaecol 1992; 99: 547–53PubMedCrossRefGoogle Scholar
  5. 5.
    Moodley J, Daya P. Eclampsia: a continuing problem in developing countries. Int J Obstet Gynaecol 1993; 44: 9–14CrossRefGoogle Scholar
  6. 6.
    Maharaj B, Moodley J. Management of hypertension in pregnancy. Cont Med Educ 1991; 12: 1581–89Google Scholar
  7. 7.
    Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynaecol 1988; 158: 892–8Google Scholar
  8. 8.
    Anumba DOC, Robson SC. Management of pre-eclampsia and the HELLP syndrome. Curr Opin Obstet Gynaecol 1999; 11: 149–56CrossRefGoogle Scholar
  9. 9.
    Douglas KA, Redman CWG. Eclampsia in the United Kingdom. BMJ 1994; 309: 1395–400PubMedCrossRefGoogle Scholar
  10. 10.
    World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the incidence of hypertension in pregnancy. Am J Obstet Gynaecol 1988; 158: 80–3Google Scholar
  11. 11.
    Crowther CA. Eclampsia at Harare Maternity Hospital. An epidemiological study. S Afr Med J 1985; 68: 927–9PubMedGoogle Scholar
  12. 12.
    Bergstrom S, Povey G, Songane F, et al. Seasonal incidence of eclampsia and its relationship to meterological data in Mozambique. J Perinatol Med 1992; 20: 153–8CrossRefGoogle Scholar
  13. 13.
    Sibai BM. Chronic hypertension in pregnancy. Clin Perinatol 1991; 18: 833–44PubMedGoogle Scholar
  14. 14.
    Kyle P, Redman CWG. Comparative risk benefit assessment of drugs used in the management of hypertension in pregnancy. Drug Saf 1992; 7: 223–34PubMedCrossRefGoogle Scholar
  15. 15.
    Bott-Kanner G, Hirsch M, Friedman S. Antihypertensive therapy in the management of hypertension-a clinical double blind study of pindolol. Clin Exp Hypertens (B) 1992; 11B: 207–20Google Scholar
  16. 16.
    Hjertberg R, Beitrage P, Hanson U. Conservative treatment of mild and moderate hypertension in pregnancy. Acta Obstet Gynaecol Scand 1992; 71: 439–46CrossRefGoogle Scholar
  17. 17.
    Davey DA, Anthony J. Hypertension and antihypertensive drugs in pregnancy. Cardiovasc J S Afr 1990; 3: 154–61Google Scholar
  18. 18.
    Girndt J. Pregnancy in women with diabetic nephropathy: a clear indication for antihypertensive treatment. Zentralbl Gynakol 1994; 116: 362–4PubMedGoogle Scholar
  19. 19.
    Biesenbach G, Stoger H, Zazgornik J. Influence of pregnancy on progression of diabetic nephropathy and subsequent requirement of renal replacement therapy in female type 1 diabetic patients with impaired renal function. Nephrol Dialysis Transplant 1992; 7: 105–9Google Scholar
  20. 20.
    Calhoun DA, Oparil S. Treatment of hypertensive crises. N Engl J Med 1990; 332: 1177–83Google Scholar
  21. 21.
    Finnery AAJ. Hypertensive encephalopathies. Am J Med 1972; 52: 672–8CrossRefGoogle Scholar
  22. 22.
    Smith DW. Recognisable patterns of human malformations. 3rd ed. Philadelphia (PA): WB Saunders, 1980Google Scholar
  23. 23.
    Mirkin BL, Singh S. Placental transfer of pharmacologically active molecules. In: Mirkin BL, editor. Perinatal pharmacology and therapeutics. New York: Academic Press, 1976: 57–70Google Scholar
  24. 24.
    Garland M. Pharmacology of drug transfer across placenta. Obstet Gynaecol Clin North Am 1998; 25(1): 21–42CrossRefGoogle Scholar
  25. 25.
    Krauer B, Krauer F, Hytten FE. Drug disposition and pharmacokinetics in the maternal placental-fetal unit. Pharmacol Ther 1980; 10: 301–28PubMedCrossRefGoogle Scholar
  26. 26.
    Perruca E, Crema A. Plasma protein binding of drugs in pregnancy. Clin Pharmacokinet 1982; 7: 336–52CrossRefGoogle Scholar
  27. 27.
    Noschel H, Peiker G, Muller M. Pharmacokinetics during pregnancy and delivery. Biol Res Pregnancy 1982; 3: 66–73Google Scholar
  28. 28.
    Hill MD, Abramson FP. The significance of plasma protein binding on the fetal/maternal distribution of drugs at steady state. Clin Pharmacokinet 1988; 14: 156–70PubMedCrossRefGoogle Scholar
  29. 29.
    Morgan DJ. Drug disposition in the mother and fetus. Clin Exp Pharmacol Physiol 1997; 24(11): 869–73PubMedCrossRefGoogle Scholar
  30. 30.
    Ward RM. Pharmacological treatment of the fetus: clinical pharmacokinetic considerations. Clin Pharmacokinet 1995; 28(5): 343–50PubMedCrossRefGoogle Scholar
  31. 31.
    Pacific GM, Nottoli R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995; 28(3): 235–69CrossRefGoogle Scholar
  32. 32.
    Reynolds F, Knott C. Pharmacokinetics in pregnancy and placental drug transfer. Oxf Rev Reprod Biol 1989; 11: 389–449PubMedGoogle Scholar
  33. 33.
    de Swiet M. Embryology. In: de Swiet M, Chamberlain G, editors. Basic sciences in obstetrics and gynaecology. 2nd ed. Edinburgh: Churchill Livingstone, 1992: 27–52Google Scholar
  34. 34.
    Hill RM, Stern L. Drugs in pregnancy. Drugs 1979; 17: 182–97PubMedCrossRefGoogle Scholar
  35. 35.
    Juchau MR, Dyer DC. Pharmacology of the placenta. Pediatr Clin North Am 1972; 19: 65–79PubMedGoogle Scholar
  36. 36.
    Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med 1996; 335: 257–65PubMedCrossRefGoogle Scholar
  37. 37.
    Steyn W. Antihypertensive therapy in pregnancy. Specialist Med 1998; Feb: 13–8Google Scholar
  38. 38.
    Henriksen T. Hypertension in pregnancy: use of antihypertensive drugs. Acta Obstet Gynaecol Scand 1997; 76: 96–106CrossRefGoogle Scholar
  39. 39.
    Lewis PJ, Bulpitt CJ, Zuspan FP. Acomparison of current British and American practice in management of hypertension I pregnancy. J Obstet Gynaecol 1980; 1: 78–83CrossRefGoogle Scholar
  40. 40.
    Trudinger BJ, Rarik I. Attitudes to the management of hypertension in pregnancy: a survey of Australian fellows. Aust NZ J Obstet Gynaecol 1982; 22: 191–7CrossRefGoogle Scholar
  41. 41.
    Redman CWG, Roberts JM. Management of pre-eclampsia. Lancet 1983; 341: 1451–4CrossRefGoogle Scholar
  42. 42.
    Woods JR, Brinkman CR. The treatment of gestational hypertension. J Reprod Med 1975; 15: 195–201PubMedGoogle Scholar
  43. 43.
    Fidler J, Smith V, Fayers P. Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. BMJ 1983; 286: 1927–30PubMedCrossRefGoogle Scholar
  44. 44.
    Dunstead M, Moar VA, Redman CWG. Infant growth and development following treatment of maternal hypertension. Lancet 1980; I: 705Google Scholar
  45. 45.
    Cockburn J, Moar VA, Qunsted M, et al. Final report of study on hypertension during pregnancy: the effects of specific treatment on the growth and development of the children. Lancet 1982; I: 647–9CrossRefGoogle Scholar
  46. 46.
    Moar VA, Jefferies M, Mutch L. Neonatal head circumference and the treatment of maternal hypertension. Br J Obstet Gynaecol 1978; 85: 933–7PubMedCrossRefGoogle Scholar
  47. 47.
    National High Blood Pressure Education Program Working Group Report on high blood pressure in pregnancy. Am J Obstet Gynaecol 1990; 163: 1689–712Google Scholar
  48. 48.
    Levin AC, Doering PL, Hatton RC. Use of nifedipine in the hypertensive disorders of pregnancy. Ann Pharmacother 1994; 28: 1871–8Google Scholar
  49. 49.
    Lindheimer MD. Hypertension in pregnancy. Hypertension 1993; 127: 127–37CrossRefGoogle Scholar
  50. 50.
    Wide-Swensson D, Montan S, Arulkumaran S, et al. Effect of methyldopa and isradipine on fetal heart rate pattern assessed by computerized cardiotocography in human pregnancy. Am J Obstet Gynaecol 1993; 169: 1581–5Google Scholar
  51. 51.
    Hutton JD, James DK, Stirrat GM, et al. Management of severe pre-eclampsia and eclampsia by UK consultants. Br J Obstet Gynaecol 1992; 99: 554–6PubMedCrossRefGoogle Scholar
  52. 52.
    Lund-Johansen P. Pharmacology of combined alpha-beta-blockade. Drugs 1984; 28: 35–50PubMedCrossRefGoogle Scholar
  53. 53.
    Michael CA. The evaluation of labetalol in the treatment of hypertension complicating pregnancy. Br J Clin Pharmacol 1982; 3 Suppl.: 127–36CrossRefGoogle Scholar
  54. 54.
    Sibai BA, Gonzalez AR, Mabie WC, et al. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of pre-eclampsia remote from term. Am J Obstet Gynaecol 1987; 70: 323–7Google Scholar
  55. 55.
    Pickles CJ, Broughton-Pipkin F, Symonds EM. A randomised placebo controlled trial of labetalol in treatment of mild to moderate pregnancy induced hypertension. Br J Obstet Gynaecol 1992; 99: 964–8PubMedCrossRefGoogle Scholar
  56. 56.
    Sibai BA, Mabie WC, Shamsa F, et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynaecol 1990; 162: 960–7Google Scholar
  57. 57.
    Redman CWG. Hypertension in pregnancy. In: de Swiet M. editor. Medical disorders in obstetric practice. London: Blackwell Science, 1995: 182–225Google Scholar
  58. 58.
    Danielsson BR, Reiland S, Rundqvist E, et al. Digital defects induced by vasodilating agents: relationship to reduction in uteroplacental blood flow. Teratology 1989; 40(4): 351–8PubMedCrossRefGoogle Scholar
  59. 59.
    Danielsson BR, Daneilson M, Reiland S, et al. Histological and in vitro studies supporting decreased uteroplacental blood flow as explanation for digital defects after administration of vasodilators. Teratology 1990; 41(2): 185–93PubMedCrossRefGoogle Scholar
  60. 60.
    Magee L, Schick B, Donnerfeld A. The safety of calcium channel blockers in pregnancy: a prospective multicenter cohort study. Am J Obstet Gynaecol 1996; 174: 823–8CrossRefGoogle Scholar
  61. 61.
    Waisman G, Mayorga L, Amera M. Magnesium plus nifedipine: potetiation of hypotensive effects in pre-eclampsia? Am J Obstet Gynaecol 1989; 159: 308–9Google Scholar
  62. 62.
    Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynaecol 1989; 161: 35–6Google Scholar
  63. 63.
    Constantine G, Beevers DG, Reynolds AL, et al. Nifedipine as a second line antihypertensive drug in pregnancy. Br J Obstet Gynaecol 1987; 94: 1136–42PubMedCrossRefGoogle Scholar
  64. 64.
    Ulmsten U. Treatment of normotensive and and hypertensive patient with pre-term labor with oral nifedipine, a calcium antagonist. Arch Gynaecol 1984; 236: 69–72CrossRefGoogle Scholar
  65. 65.
    Sibai BM, Barton JR, Sherif A, et al. A randomised prospective study of nifedipine and bedrest versus bed rest alone in the management of pre-eclampsia remote from term. Am J Obstet Gynaecol 1992; 167: 879–84Google Scholar
  66. 66.
    Danti L, Valcamonico A, Soregaroli B, et al. Fetal and maternal doppler modifications during therapy with antihypertensive drugs. J Maternal Fetal Invest 1994; 4: 19–23Google Scholar
  67. 67.
    Wide-Swensson DH, Ingemarsson I, Lunell NO. Calcium channel blockade (isradipine) in the treatment of hypertension in pregnancy: a randomised placebo controlled study. Am J Obstet Gynaecol 1995; 173 (Part 1): 872–8CrossRefGoogle Scholar
  68. 68.
    Lunell NO, Garoff L, Grunewald C. Isradipine, a new calcium antagonist: effects on maternal and fetal haemodynamics. J Cardiovasc Pharmacol 1991; 18Suppl. 3: S37–40PubMedGoogle Scholar
  69. 69.
    Lunell NO, Bondesson U, Grunewald C, et al. Transplacental passage of isradipine in the treatment of pregnancy induced hypertension. Am J Hypertens 1993; 6Suppl. 3: 110–1SGoogle Scholar
  70. 70.
    Belfort MA, Saade GR, Moise KJ. Nimodipine in the management of pre-eclampsia: maternal and fetal effects. Am J Obstet Gynaecol 1994; 171: 417–24Google Scholar
  71. 71.
    Carbonne B, Jannet D, Touboul C. Nicardipine treatment of hypertension during pregnancy. Obstet Gynaecol 1993; 81: 908–14Google Scholar
  72. 72.
    Allen J, Maigaard S, Jacobsen P. Acute effects of nitrendipine in pregnancy. Br J Obstet Gynaecol 1987; 94: 222–6PubMedCrossRefGoogle Scholar
  73. 73.
    Wide-Swensson DH, Montai F, Ingemarsson I. How Swedish obstetricians manage hypertensive disorders of pregnancy. Acta Obstet Gynaecol Scand 1994; 73: 619–24CrossRefGoogle Scholar
  74. 74.
    Ingemarsson I, Wide-Swenson D, Andersson KE. Maternal and fetal cardiovascular changes after intravenous injection of isradipine to pregnant women. Drugs 1990; 40Suppl. 2: 58–9PubMedCrossRefGoogle Scholar
  75. 75.
    Maharaj B, Khedun SM, Moodley J, et al. Intravenous isradipine in the management of severe hypertension in pregnancy. Hypertens Pregnancy 1997; 16: 1–9CrossRefGoogle Scholar
  76. 76.
    Phippard AF, Fischer WE, Horvath JS, et al. Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension. Med J Aust 1991; 154: 378–82PubMedGoogle Scholar
  77. 77.
    Gallery EDM, Saunders DM, Hunyor SN, et al. Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy. BMJ 1979; 1: 1591–4PubMedCrossRefGoogle Scholar
  78. 78.
    Hogstedt S, Lindeberg S, Axelsson O. A prospective controlled trial of metoprolol-hydralazine treatment in hypertension during pregnancy. Acta Obstet Gynaecol Scand 1985; 64: 505–10CrossRefGoogle Scholar
  79. 79.
    Rosenfeld J, Bottkanner G, Boner G. Treatment of hypertension during pregnancy with hydralazine monotherapy or with combined therapy with hydralazine and pindolol. Euro J Obstet Gynaecol Reprod Biol 1986; 22: 197–204CrossRefGoogle Scholar
  80. 80.
    Widerlov E, Karlman I, Storsater J. Hydralazine induced neonatal thrombocytopaenia. N Engl J Med 1980; 303: 1235PubMedGoogle Scholar
  81. 81.
    Schneider H, Proegler M. Placental transfer of beta-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue. Am J Obstet Gynaecol 1988; 159: 42–7Google Scholar
  82. 82.
    Rubin PC, Butters L, Clark DM, et al. Placebo controlled trial of atenolol in the treatment of pregnancy-associated hypertension. Lancet 1983; I: 431–4Google Scholar
  83. 83.
    Gallery EDM, Ross MR, Gyory AZ. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. BMJ 1985; 291: 563–6PubMedCrossRefGoogle Scholar
  84. 84.
    Montan S, Ingemarsson I, Marsal K, et al. Randomised controlled trial of atenolol and pindolol in human pregnancy: effect on fetal haemodynamics. BMJ 1992; 304: 946–9PubMedCrossRefGoogle Scholar
  85. 85.
    Dubois D, Petitcolas J, Temperville B, et al. Treatment of hypertension in pregnancy with β-adrenoceptor antagonists. Br J Clin Pharmacol 1982; 13: 375–8SCrossRefGoogle Scholar
  86. 86.
    Lardoux H, Gerard J, Elazquez G, et al. Which beta-blocker in pregnancy-induced hypertension? Lancet 1983; II: 1194–8CrossRefGoogle Scholar
  87. 87.
    Pruyn SC, Phelan JP, Buchanan G. Long-term therapy in pregnancy. Maternal and fetal outcome. Am J Obstet Gynaecol 1979; 135: 485–9Google Scholar
  88. 88.
    Habib A, McCarthy JS. Effect on the neonate of propanolol administered during pregnancy. J Paediatr 1977; 91: 808–11CrossRefGoogle Scholar
  89. 89.
    Van Zwieten PA, Timmermans PB. Differential pharmacological properties of beta-adrenoceptor blocking drugs. J Cardiovasc Pharmacol 1983; 5Suppl. 1: S1–7PubMedCrossRefGoogle Scholar
  90. 90.
    Lieberman BA, Stirrat GM, Cohen SL. The possible adverse effects of propanolol on the fetus in pregnancies complicated by severe hypertension. Br J Obstet Gynaecol 1978; 85: 678–83PubMedCrossRefGoogle Scholar
  91. 91.
    Wichman K, Ryden G, Karlberg B. A placebo controlled trial of metoprolol in the treatment of hypertension in pregnancy. Scand J Clin Lab Invest 1984; 44Suppl. 169: 90–5CrossRefGoogle Scholar
  92. 92.
    Sandstrom B. Antihypertensive treatment with the adrenergic beta-receptor blocker metoproplol during pregnancy. Gynaecol Obstet Invest 1978; 9: 195–204CrossRefGoogle Scholar
  93. 93.
    Plouin PF, Breart G, Llado J, et al. Randomised comparison of early with conservative use of hypertensive drugs in the management of pregnancy induced hypertension. Br J Obstet Gynaecol 1990, 97: 134–41PubMedCrossRefGoogle Scholar
  94. 94.
    Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension in pregnancy. BMJ 1990; 301: 587–9PubMedCrossRefGoogle Scholar
  95. 95.
    Lip GYH, Beevers M, Churchill D, et al. Effect of atenolol on birth weight. Am J Cardiol 1997; 79: 1436–8PubMedCrossRefGoogle Scholar
  96. 96.
    Lydakis C, Lip GYH, Beevers M, et al. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens 1999; 12: 541–7PubMedCrossRefGoogle Scholar
  97. 97.
    Rubin PC, Butters L, Lowe RA, et al. Clinical pharmacological studies with prazosin during pregnancy complicated hypertension. Br J Clin Pharmacol 1983; 16: 543–7PubMedCrossRefGoogle Scholar
  98. 98.
    Paran E, Holzberg G, Mazor M, et al. Beta adrenergic blocking agents in the treatment of pregnancy induced hypertension. Int J Pharm Ther 1995; 33: 119–23Google Scholar
  99. 99.
    Dommisse J, Davey DA, Roos PJ. Prazosin and oxprenolol therapy in pregnancy hypertension. S Afr Med J 1983; 64: 231–3PubMedGoogle Scholar
  100. 100.
    Devoe LD, O’Dell BE, Castillo RA, et al. Metastatic phaechromocytoma in pregnancy and fetal biophysical assessment after maternal administration of alpha-adrenergic, beta adrenergic, and dopamine antagonist. Obstet Gynaecol 1986; 68 Suppl.: 15–8SGoogle Scholar
  101. 101.
    Bourget P, Fernandez H, Ribou F, et al. Weak placental passage of prazosin during third trimester of pregnancy. 3 cases. J Gynaecol Obstet Biol Reprod 1993; 22: 871–4Google Scholar
  102. 102.
    Redman CW. The management of hypertension in pregnancy. Scand J Clin Lab Invest 1984; 169 Suppl.: 61–72CrossRefGoogle Scholar
  103. 103.
    Collins R, Yusuf S, Peto R. Overview of randomised trials of diuretics in pregnancy. BMJ 1985; 290: 17–23PubMedCrossRefGoogle Scholar
  104. 104.
    Chari RS, Friedman SA, Sibai BM. Antihypertensive therapy during pregnancy. Fetal Maternal Med Rev 1995; 7: 61–75CrossRefGoogle Scholar
  105. 105.
    Sibai BM, Addella TN, Anderson GD. Plasma volume determination in pregnancies complicated with chronic hypertension and intrauterine demise. Obstet Gynaecol 1982; 60: 174–8Google Scholar
  106. 106.
    Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Am J Obstet Gynaecol 1984; 150: 831–5Google Scholar
  107. 107.
    Folb PI, Dukes MNG. Diuretics. In: Folb PI, Dukes MNG, editors. Drug safety in pregnancy. New York (NY): Elsevier Science, 1990: 169–71Google Scholar
  108. 108.
    Dominguez LJ, Barbagallo M, Kattah W, et al. Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects. Am J Hypertens 1995; 8: 808–14PubMedCrossRefGoogle Scholar
  109. 109.
    Bjorck S, Mulec H, Johnsen SA, et al. Renal protective effect of enalapril in diabetic nephropathy. BMJ 1992; 304: 339–43PubMedCrossRefGoogle Scholar
  110. 110.
    Brent R, Beckman D. Angiotensin converting enzyme inhibitors, an emvbryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology 1991; 43: 543–6PubMedCrossRefGoogle Scholar
  111. 111.
    Buttar HS. An overview of the influence of ACE inhibitors on fetal placental circulation and perinatal development. Mol Cell Biol 1997; 176(1–2): 61–71Google Scholar
  112. 112.
    Barr M, Cohen M. ACE inhibitor fetopathy and hypocalvarium: the kidney skull connection. Teratology 1991; 44: 485–95PubMedCrossRefGoogle Scholar
  113. 113.
    Hanssens M, Keirse M, Venkelcom F. Fetal and neonatal effects of treatment with angiotensin converting enzyme inhibitors. Obstet Gynaecol 1991; 78: 128–33Google Scholar
  114. 114.
    Rossa FW, Bosco LA, Graham CF, et al. Neonatal anuria with maternal angiotensin-converting enzyme inhibition. Obstet Gynecol 1989; 74: 371–4Google Scholar
  115. 115.
    Bar J, Hod M, Merlob P. Angiotensin converting enzyme inhibitor use in the first trimester of pregnancy. Int J Risk Safety Med 1997; 10: 23–6Google Scholar
  116. 116.
    Lip GYH, Churchill D, Beevers M, et al. Angiotensin converting enzyme inhibitors in early pregnancy. Lancet 1997; 350: 1446–7PubMedCrossRefGoogle Scholar
  117. 117.
    Steffensen FH, Nielsen GL, Sorensen HT, et al. Pregnancy outcome with ACE-inhibitors use in early pregnancy [letter]. Lancet 1998; 351(9102): 596PubMedCrossRefGoogle Scholar
  118. 118.
    Yip SK, Leung TN, Fung HY. Exposure to angiotensin converting enzyme inhibitors during first trimester: is it safe. Acta Obstet Gynaecol Scand 1998; 77(5): 570–1CrossRefGoogle Scholar
  119. 119.
    Johnston CI. Angiotension 11 antagonists: focus on losartan. Lancet 1995; 346: 1403–7PubMedCrossRefGoogle Scholar
  120. 120.
    Barron VM, Murphy MD, Lindheimer MD. Management of hypertension during pregnancy. In: Laragh JH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis and management. New York (NY): Raven Press, 1990: 1809–27Google Scholar
  121. 121.
    Mabie WC, Gonzales AR, Sibai BM. A comparative trial of labetalol and hydralazine in acute management of severe hypertension complicating pregnancy. Obstet Gynaecol 1987; 70: 328–31Google Scholar
  122. 122.
    Gudmundsson S, Gennser G, Maral K. Effects of hydralazine on placental and renal circulation in pre-eclampsia. Acta Obstet Gynaecol Scand 1995; 74: 415–8CrossRefGoogle Scholar
  123. 123.
    Silver H. Acute hypertensive crises in pregnancy. Med Clin North Am 1989; 73: 623–37PubMedGoogle Scholar
  124. 124.
    Vink GJ, Moodley JH, Philpott RH. Effect of dihydralazine on the fetus in the treatment of maternal hypertension. Obstet Gynaecol 1980; 55: 519–22Google Scholar
  125. 125.
    Bhorat IE, Naidoo DP, Rout CC. Malignant ventricular arrhythmias in eclampsia. A comparison of labetalol with dihydralazine. Am J Obstet Gynaecol 1993; 168: 1292–6Google Scholar
  126. 126.
    Walker JJ, Greer I, Calder AA. Treatment of acute pregnany related hypertension: labetalol and hydralazine compared. Postgrad Med J 1983; 59: 168–70PubMedGoogle Scholar
  127. 127.
    Garden A, Davey DA, Dommisse J. Intravenous labetalol and intravenous dihydralazine in severe hypertension in pregnancy. Clin Exp Hypertens 1982; 1: 371–83Google Scholar
  128. 128.
    Ashe RG, Moodley J, Richards A, et al. Comparison of labetalol and dihydralazine in hypertensive emergencies of pregnancy. S Afr Med J 1987; 71: 354–6PubMedGoogle Scholar
  129. 129.
    Lunell NO, Nylund L, Lewander R, et al. Acute effects of antihypertensive drug, labetalol, on uteroplacental blood flow. Br J Obstet Gynaecol 1982; 89: 640–4PubMedCrossRefGoogle Scholar
  130. 130.
    Jouppila P, Kirkinen P, Koivula A, et al. Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in preeclampsia. Br J Obstet Gynaecol 1986; 93: 543–7PubMedCrossRefGoogle Scholar
  131. 131.
    Klaar JM, Bhatt-Metha V, Donn SM. Neonatal adnergesic blockade following single dose maternal labetalol administration. Am J Perinatol 1994; 11: 91–3CrossRefGoogle Scholar
  132. 132.
    Seabe SJ, Moodley J, Becker P. Nifedipine in acute hypertensive emergencies in pregnancy. S Afr Med J 1989; 76: 248–50PubMedGoogle Scholar
  133. 133.
    Martins-Costa S, Ramos JG, Barros E, et al. Randomised controlled trial of hydralazine versus nifedipine in pre-eclmaptic women with acute hypertension. Clin Exp Hypertens Pregnancy 1992; B11(1): 25–44CrossRefGoogle Scholar
  134. 134.
    Fenakel K, Fenakel G, Appelman Z, et al. Nifedipine in the treatment of severe pre-ecalmpsia. Obstet Gynaecol 1991; 77: 331–7Google Scholar
  135. 135.
    Lindow SW, Davies N, Davey DA, et al. Effect of sublingual nifedipine on uteroplacental blood flow in hypertensive pregnancy. Br J Obstet Gynaecol 1988; 95: 1276–81PubMedCrossRefGoogle Scholar
  136. 136.
    Pirhonen JP, Erkkola RU, Ekblad UU. Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. Obstet Gynaecol 1990; 76: 37–41CrossRefGoogle Scholar
  137. 137.
    Moretti MM, Fairlie FM, Akl S, et al. The effect of nifedipine therapy on fetal and placental doppler waveforms in preeclampsia remote from term. Am J Obstet Gynaecol 1990; 163: 1844–8Google Scholar
  138. 138.
    Hanretty KP, Whittle JM, Rubin PC. Effect of nifedipine on doppler flow velocity waveforms in severe pre-eclampsia. BMJ 1989; 299: 1205–6PubMedCrossRefGoogle Scholar
  139. 139.
    Walters BNJ, Redman CWG. Treatment of severe pregnancy associated hypertension with calcium antagonist nifedipine. Br J Obstet Gynaecol 1984; 91: 330–6PubMedCrossRefGoogle Scholar
  140. 140.
    Davis WB, Wells SR, Kuller JA, et al. Analysis of the risks associated with calcium channel blockade: implications for the obstetricians-gynaecologist. Obstet Gynaecol Surg 1997; 52(3): 198–201CrossRefGoogle Scholar
  141. 141.
    Brown MA, McCowan LME, North RA, et al. Withdrawal of nifedipine capsules: jeopardising the treatment of acute severe hypertension in pregnancy. Med J Aust 1997; 166: 640–3PubMedGoogle Scholar
  142. 142.
    Neuman J, Weiss B, Rabello Y. Diazoxide for acute control of severe hypertension complicating pregnancy. A pilot study. Obstet Gynaecol 1979; 53: 50–5Google Scholar
  143. 143.
    Sankar D, Moodley J. Low doses of diazoxide in the emergency management of severe hypertension in pregnancy. S Afr Med J 1984; 65: 279–80PubMedGoogle Scholar
  144. 144.
    Dudley DKL. Minibolus diazoxide in the management of severe hypertension in pregnancy. Am J Obstet Gynaecol 1985; 151: 196–200Google Scholar
  145. 145.
    Smith HM, Aynsley-Green A, Redman CWG. Neonatal hypoglycaemia after prolonged maternal treatment with diazoxide. BMJ Clin Res 1982; 284: 1234–9CrossRefGoogle Scholar
  146. 146.
    Baker L, Stanley CA. Neonatal hypoglycaemia. Curr Ther Endocrinol Metab 1994; 5: 376–80PubMedGoogle Scholar
  147. 147.
    Shoemaker CT, Meyers M. Sodium nitroprusside for control of severe hypertensive disease of pregnancy. A case report and discussion of potential toxicity. Am J Obstet Gynaecol 1984; 149: 171–3Google Scholar
  148. 148.
    Godlin RC. Fetal and maternal effects of sodium nitroprusside. Am J Obstet Gynaecol 1983; 146: 350–1Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Shaun M. Khedun
    • 1
  • Breminand Maharaj
    • 1
  • Jagidesa Moodley
    • 2
  1. 1.Department of Clinical and Experimental Pharmacology, Nelson R. Mandela School of MedicineUniversity of NatalDurbanSouth Africa
  2. 2.UN MRC Pregnancy Hypertension Research Unit, Nelson R. Mandela School of MedicineUniversity of Natal Medical SchoolCongella 4013, DurbanSouth Africa

Personalised recommendations