Antihypertensives Therapy And Monitoring In Pre-Eclampsia: Role Of The Pharmacist
Main Article Content
Keywords
antihypertensives in pre-eclampsia, obstetrics, hypertension in pregnancy, monitoring, pharmacists’ role
Abstract
Pre-eclampsia is an obstetric disorder that affects the prognosis of pregnancy, resulting in complications or mortalities. It is typically associated with hypertension which should be managed pharmacologically to protect the health of the mother and the fetus. Yet, not much is known about pharmacists’ roles and commitment to pre-eclampsia management. In this review, we update pharmacists on antihypertensives indicated in pre-eclampsia as well as parameters they have to monitor during pharmacotherapy in line with their duty of care to women with pre-eclampsia. Using recent evidence from 16 national/international guidelines (2014-2022), we compared antihypertensives approved for use in pregnancy and highlighted major drug information that pharmacists require to optimize the use of these medications in pre-eclampsia. Intravenous labetalol, hydralazine or oral nifedipine agents are mostly indicated in pre-eclampsia with severe hypertension. In mild-moderate hypertension, oral agents such as methyldopa, labetalol, sustained released nifedipine and hydralazine are the commonest recommendations. While monitoring for maternal bronchoconstriction, neonatal bradycardia or hypoglycemia is required with the administration of intravenous labetalol; intravenous hydralazine is observed for maternal shock; nifedipine for tachycardia, headache, ankle edema and methyldopa for depression if use is extended to the postpartum period. Controlled hypertension in pre-eclampsia mitigates maternal vascular complications. Apart from early referral and counselling of pregnant women at risk, pharmacists with sound knowledge of the pharmacotherapy of pre-eclampsia could advise on appropriate antihypertensive therapy and follow on to ensure that these medicines are responsibly used for optimal outcomes. These roles by pharmacists, may reduce adverse maternal outcomes associated with pre-eclampsia.
References
2. Tsao NW, Marra CA, Lynd LD, et al. Community pharmacist surveillance of hypertension in pregnancy: Are we ready for prime time? Can Pharm J (Ott) 2014;147(5):307-15. https://doi.org/10.1177/1715163514543898.
3. Poon LC, Shennan S, Jonathan AH, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynecol Obstet 2019; 145
(Suppl 1):1-33.https://doi.org/10.1002/ijgo.12802.
4. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122(5):1122-31. https://doi.org/10.1097/01.AOG.0000437382.03963.88.
5. National Institute for Health and Care Excellence guidelines: NG-133 Hypertension in pregnancy: diagnosis and management. 2019. Available at: https://www.nice.org.uk/guidance/ng133
6. Gestational Hypertension and Pre-eclampsia: ACOG Practice Bulletin, Number 222.ObstetGynecol 2020; 135(6):e237-e260.https://doi.org/10.1097/AOG.0000000000003891.
7. WHO, Maternal mortality, Key facts, September 2019: News release, New York, Geneva. 2019. Available at: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality
8. Ananth CO, Basso O. Impact of pregnancy-induced hypertension on stillbirth and neonatal mortality. Epidemiology 2010; 21(1):118-123. https://doi.org/10.1097/EDE.0b013e3181c297af.
9. Trends in maternal mortality: 1990 to 2015: estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division, Geneva. 2015. Available at: https://www.unfpa.org/sites/default/files/pub-pdf/9789241565141_eng.pdf
10. Noubiap JJ, Bigna JJ, Nyaga UF, et al. The burden of hypertensive disorders of pregnancy in Africa: A systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2019; 21(4):479-88.https://doi.org/10.1111/jch.13514.
11. Ghana Statistical Service (GSS), Ghana.Health.Service, and ICF. Ghana Maternal Health Survey 2017. Accra: Ghana Demogr Health Surv 2018. Available at: https://dhsprogram.com/pubs/pdf/FR340/FR340.pdf
12. Backes CH, Markham K, Moorehead P, et al. Maternal pre-eclampsia and neonatal outcomes. J Pregnancy.2011;2011:214365. https://doi.org/10.1155/2011/214365.
13. Vousden N, Lawley E, Seed PT, et al. Incidence of eclampsia and related complications across 10 low and middle-resource geographical regions: Secondary analysis of a cluster randomized controlled trial. PLoS Med 2019; 16(3):e1002775. https://doi.org/10.1371/journal.pmed.1002775.
14. Abdul-Mumin A, Cotache-Condor C, Owusu SA, et al. Timing and causes of neonatal mortality in Tamale Teaching Hospital, Ghana: A retrospective study. PLoS One 2021;16(1):e0245065. https://doi.org/10.1371/journal.pone.0245065.
15. Annan GN, Asiedu Y. Predictors of neonatal deaths in Ashanti Region of Ghana: A cross-sectional study. Adv Public Health 2018; Article ID 9020914.https://doi.org/10.1155/2018/9020914
16. Roy S, Sultana K, Hossain S, et al. Knowledge of pharmacy workers on antihypertensive and anticonvulsant drugs for managing pre-eclampsia and eclampsia in Bangladesh. BMC Health Serv Res 2020; 20(1):838. https://doi.org/10.1186/s12913-020-05685-6
17. Kirk KR, Dempsey A. A systematic review of the treatment and management of pre-eclampsia and eclampsia in Bangladesh. Washington DC: Population Council 2017. https://doi.org/10.31899/rh7.1000.
18. Kattah AG, Garovic VD. The management of hypertension in pregnancy. Adv Chronic kidney Dis 2013; 20(3):229-39.https://doi.org/10.1053/j.ackd.2013.01.014.
19. Shamsi U, Saleem S, Nishtar N. Epidemiology and risk factors of pre-eclampsia; an overview of observational studies. Almeen J Med Sci 2013; 6(4): 292-300. Available at: http://ajms.alameenmedical.org/ArticlePDFs/AJMS%20V6.N4.2013%20p%20292-300.pdf
20. Republic of Ghana, Ministry of Health Standard Treatment Guidelines. 7 ed. Ghana Yamens Press Ltd, 2017. Available at: https://www.moh.gov.gh/wp-content/uploads/2020/07/GHANA-STG-2017-1.pdf
21. Umemura S, Arima H, Arima S, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res 2019; 42(9):1235–481.https://doi.org/10.1038/s41440-019-0284-9.
22. Rabi DM, Kerry A, McBrien KA, et al. Hypertension Canada’s 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children. Can J of Cardiol 2020; 36(5):596-624. https://doi.org/10.1016/j.cjca.2020.02.086.
23. World Health Organization, WHO recommendations: drug treatment for severe hypertension in pregnancy. Geneva: World Health Organization. Licence: CC BY-NC-SA 3.0 IGO. 2018. Available at:
https://apps.who.int/iris/bitstream/handle/10665/277234/9789241550437-eng.pdf?ua=1
24. World Health Organization, WHO recommendations on drug treatment for non-severe hypertension in pregnancy. Geneva: World Health Organization, Licence: CC BY-NC-SA 3.0 IGO. 2020. Available at: https://apps.who.int/iris/bitstream/handle/10665/333816/9789240008793-eng.pdf
25. Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy 2019 National guideline. S Afr Med J 2019;109(9):12723. http://www.samj.org.za/index.php/samj/article/view/12723
26. Magee LA, Hall D, van der Merwe JL, et al. Fluids, drugs and transfusion, the FIGO textbook of pregnancy hypertension: an evidence-based guide to monitoring, prevention and management, London. The Global Library of Women’s Medicine, 2016;133-166. https://www.glowm.com/pdf/NEW-Pregnancy_Hypertension-chapter8.pdf
27. Brown MA, Magee LA, Kenny LK, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension 2018;72(1):24-43. https://doi.org/10.1161/hypertensionaha.117.10803.
28. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. ESC Scientific Document Group, 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur heart J 2018;39(34):3165-241.https://doi.org/10.1093/eurheartj/ehy340.
29. Lowe SA, Bowyer L, Lust K, et al. SOMANZ guidelines for the management of hypertensive disorders of pregnancy. Aust N Z J ObstetGynecol2015; 55(5): e1–e29.https://doi.org/10.1111/ajo.12399.
30. Tykarski A, Narkiewicz K, Gaciong Z, et al. 2015 guidelines for the management of hypertension. Recommendations of the Polish Society of Hypertension—short version. Kardiol Pol 2015;73(8):676-700. https://doi.org/10.5603/KP.2015.0157.
31. Kim KI, Ihm SH, Kim GH, et al. 2018 Korean society of hypertension guidelines for the management of hypertension: part III-hypertension in special situations. Clin hypertens 2019; 25(19). https://doi.org/10.1186/s40885-019-0123-y
32. Gillon TE, Pels A, von Dadelszen P, et al. Hypertensive disorders of pregnancy: a systematic review of international clinical practice guidelines. PLoS One 2014;9(12):e113715.https://doi.org/10.1371/journal.pone.0113715.
33. Garovic, VD, Dechend R, Easterling T, et al. Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association. Hypertension 2022. 79(2):e21-e41. https://doi.org 10.1161/HYP.0000000000000208
34. Awaludin A, Rahayu C, Daud NAA, Zakiyah N. Antihypertensive medications for severe hypertension in pregnancy: A Systematic Review and Meta-Analysis. In Healthcare (Basel) 2022;10(2):325. https://doi.org/10.3390/healthcare10020325
35. Barroso WKS, Rodrigues CIS, Bortolotto LA, et al. Brazilian guidelines of hypertension–2020. Arq Bras Cardiol 2021; 116(3):516-658.https://doi.org/10.36660/abc.20201238
36. Hart TD, Harris BM. Pre-eclampsia revisited. US Pharmacist 2012;37(9):48-53. https://www.uspharmacist.com/article/preeclampsia-revisited
37. Aali, SB, Nejad SS. Nifedipine or hydralazine as a first-line agent to control hypertension in severe pre-eclampsia. Acta Obstet Gynecol Scand 2002; 81(1): 25-30.https://doi.org/10.1034/j.1600-0412.2002.810105.x.
38. Ibrahim MM. Egyptian hypertension guidelines. Egypt Heart J 2014; 66(2):79-132. Available athttps://scholar.cu.edu.eg/?q=ghadayoussef/files/egyptian_htn_guidelines_publication.pdf
39. Biola A, Givertz MM, Colucci WC. Inotropic and vasoactive agents in cardiac intensive care. Brown DL (editors). 3 ed. Elsevier, 2019:394-401.e3. https://doi.org/10.1016/B978-0-323-52993-8.00037-0
40. Aronson JK. Labetalol. Meyler's side effects of drugs. 16 ed. UK, Elsevier, 2016:439-440. https://doi.org/10.1016/B978-0-444-53717-1.00951-3
41. Christof S, Paul P, Richard KM. Drugs during pregnancy and lactation. Treatment options and risk assessment. 3 ed. UK, Elsevier. 2015. Available at https://rudiapt.files.wordpress.com/2017/11/drugs-during-pregnancy-and-lactation-3rd-ed-2015.pdf
42. Maclean AB, Doig JR, Aickin DR. Hypovolemia, pre-eclampsia and diuretics. Br J Obstet Gynecol 1978; 85(8):597-601.https://doi.org/10.1111/j.1471-0528.1978.tb14927.x.
43. Medsafe, ACE Inhibitors in early pregnancy. 1998. Available at
https://medsafe.govt.nz/profs/puarticles/aceinhibitors.htm (accessed on: October 29, 2022).
44. American Pharmacists Association. Lexicom drug information handbook. 25 ed. USA, Wolters Kluwer, 2016.
45. Miller M, Kerndt C, Maani CV. Labetalol. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK534787/ (assessed on Sept 10, 2022)
46. Khatri R, Fallon JK, Sykes C, et al. Pregnancy-related hormones increase UGT1A1-mediated labetalol metabolism in human hepatocytes. Front Pharmacol 2021;12:655320. https://doi.org/10.3389/fphar.2021.655320.
47. Easterling TR. Pharmacological management of hypertension in pregnancy. Semin Perinatol 2014; 38(8): 487-95.https://doi.org/10.1053/j.semperi.2014.08.016.
48. PubChem [Internent]. Bethesda (MD): National library of medicine (US), National center for biotechnology information 2004, PubChem compound summary for CID 3869, Labetalol, 2022. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Labetalol (accessed on Sept 12, 2022)
49. Carvalho TM, Cavalli R, Cunha SP, et al. Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients. Eur J clin Pharmacol 2011; 67(1):55–61. https://doi.org/10.1007/s00228-010-0896-0.
50. Joint Formulary Committee. British national formulary 83. London: BMJ Publishing and the Royal Pharmaceutical Society. 2022.
51. Klarr JM, Bhatt-Mehta V, Donn SM. Neonatal adrenergic blockade following single dose maternal labetalol administration. Am J Perinatol 1994;11(2):91-3.https://doi.org/10.1055/s-2007-994563
52. Campbell NR, Campbell RR, Hasinoff BB. Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism. Clin Invest Med 1990; 13(6): 329-32.https://eurekamag.com/research/007/347/007347729.php
53. Gupta M, Al Khalili Y. Methyldopa. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK551671/. (accessed on Sept 14, 2022)
54. Nayak AS, Nachane HB. Risk analysis of suicidal ideations and postpartum depression with antenatal alpha methyldopa use. Asian J Psychiatr 2018;38:42-44.https://doi.org/10.1016/j.ajp.2018.10.024.
55. Wiciński M, Malinowski B, Puk O, et al. Methyldopa as an inductor of postpartum depression and maternal blues: A review. Biomed Pharmacother2020; 127(110196).https://doi.org/10.1016/j.biopha.2020.110196.
56. Herman LL, Bruss ZB, Tivakaran VS. Hydralazine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK470296/ (accessed on Sept 15, 2022)
57. Buchmann E.J. Management of hypertension. In: Sliwa K, Anthony J. (eds) Cardiac drugs in pregnancy. Current cardiovascular therapy. 1 ed. Springer, London. 2014:11-34. https://doi.org/10.1007/978-1-4471-5472-3_2
58. Andrès E, Mourot-Cottet R. Idiosyncratic drug-induced severe neutropenia and agranulocytosis: State of the Art. IntechOpen 2018;78769.https://doi.org/10.5772/intechopen.78769.
59. Tsujimoto G, Horai Y, Ishizaki T, Itoh K. Hydralazine-induced peripheral neuropathy seen in a Japanese slow acetylator patient. Br J Clin Pharmacol 1981; 11(6):622-
25.https://doi.org/10.1111/j.1365-2125.1981.tb01181.x.
60. Iyer P, Dirweesh A, Zijoo R. Hydralazine induced lupus syndrome presenting with recurrent pericardial effusion and a negative antinuclear antibody. Case Rep Rheumatol 2017; 2017:5245904. https://doi.org/10.1155/2017/5245904.
61. Khan KM, Patel J, Schaefer TJ. Nifedipine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK537052/ (accessed on Sept 17, 2022)
62. Smith P, Anthony J, Johanson R. Nifedipine in pregnancy. BJOG 2000;107(3):299-307.https://doi.org/10.1111/j.1471-0528.2000.tb13222.x.
63. Cohan JA, Checcio LM. Nifedipine in the management of hypertensive emergencies: report of two cases and review of the literature. Am J Emerg Med 1985;3(6):524–30. https://doi.org/10.1016/0735-6757(85)90164-0.
64. Prevost RR, Aki SA, Whybrew WD, Sibai BM. Oral Nifedipine Pharmacokinetics in pregnancy-induced hypertension. Pharmacotherapy 1992; 12(3):174-7.https://doi.org/10.1002/j.1875-9114.1992.tb04505.x