Pharmacological Interactions on Blood Pressure Control in Arterial Hypertension, An Issue not to be Overlooked

Author(s): Michele M. Ciulla, Chiara Benfenati, Enrico Gallazzi, Patrizia Vivona, Roberto Meazza, Federico Lombardi

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)

Volume 15 , Issue 3 , 2015

Become EABM
Become Reviewer

Graphical Abstract:


Our vision of long-term treatment strategies for the prevention of target organ damage and eventually cardiovascular morbidity and mortality in essential arterial hypertension needs to be continually monitored and updated for at least three issues:

1 - the achievement of target pressure required to obtain the expected benefit needs continuous monitoring, a dose adjustment of the drug and, often, the use of combination therapies;

2 - the chronic use of certain drugs, even in combination, is associated with the possible onset of side effects;

3 - increasing of population life expectancy is inevitably associated with in an increase in drugs use with the unavoidable occurrence of adverse drug reactions, some of which can interfere with blood pressure control.

These issues, still poorly studied, pose considerable problems in applying proper strategies for prevention. In this review, we will evaluate the goals of antihypertensive therapy, and its weak spots, such as the frequent side effects, that lead to poor therapy compliance. Moreover, we will review the interactions between antihypertensive and drugs used for other common disease, and their importance in not achieving the expected blood pressure reduction.

Keywords: Arterial hypertension, drug interactions, drug side effects, pharmacotheraphy, target blood pressure, treatment adherence.

National High Blood Pressure Education P. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda (MD); National Heart, Lung, and Blood Institute: (US), 2004.
Mancia, G.; Fagard, R.; Narkiewicz, K.; Redon, J.; Zanchetti, A.; Bohm, M.; Christiaens, T.; Cifkova, R.; De Backer, G.; Dominiczak, A.; Galderisi, M.; Grobbee, D.E.; Jaarsma, T.; Kirchhof, P.; Kjeldsen, S.E.; Laurent, S.; Manolis, A.J.; Nilsson, P.M.; Ruilope, L.M.; Schmieder, R.E.; Sirnes, P.A.; Sleight, P.; Viigimaa, M.; Waeber, B.; Zannad, F. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens., 2013, 31(7), 1281-1357.
Go, A.S.; Mozaffarian, D.; Roger, V.L.; Benjamin, E.J.; Berry, J.D.; Blaha, M.J.; Dai, S.; Ford, E.S.; Fox, C.S.; Franco, S.; Fullerton, H.J.; Gillespie, C.; Hailpern, S.M.; Heit, J.A.; Howard, V.J.; Huffman, M.D.; Judd, S.E.; Kissela, B.M.; Kittner, S.J.; Lackland, D.T.; Lichtman, J.H.; Lisabeth, L.D.; Mackey, R.H.; Magid, D.J.; Marcus, G.M.; Marelli, A.; Matchar, D.B.; McGuire, D.K.; Mohler, E.R. 3rd, Moy, C.S.; Mussolino, M.E.; Neumar, R.W.; Nichol, G.; Pandey, D.K.; Paynter, N.P.; Reeves, M.J.; Sorlie, P.D.; Stein, J.; Towfighi, A.; Turan, T.N.; Virani, S.S.; Wong, N.D.; Woo, D.; Turner, M.B. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation, 2014, 129(3), 399-410.
Franco, O.H.; Peeters, A.; Bonneux, L.; de Laet, C. Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. Hypertension, 2005, 46(2), 280-286.
Lewington, S.; Clarke, R.; Qizilbash, N.; Peto, R.; Collins, R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet, 2002, 360(9349), 1903-1913.
Criqui, M.H.; Langer, R.D.; Fronek, A.; Feigelson, H.S.; Klauber, M.R.; McCann, T.J.; Browner, D. (1992).Mortality over a period of 10 years in patients with peripheral arterial disease. N. Engl. J. Med., 326(6), 381-386.
Britton, K.A.; Gaziano, J.M.; Djousse, L. Normal systolic blood pressure and risk of heart failure in US male physicians. Eur. J. Heart Fail., 2009, 11(12), 1129-1134.
Klag, M.J.; Whelton, P.K.; Randall, B.L.; Neaton, J.D.; Brancati, F.L.; Ford, C.E.; Shulman, N.B.; Stamler, J. Blood pressure and end-stage renal disease in men. N. Engl. J. Med., 1996, 334(1), 13-18.
Collins, R.; MacMahon, S. Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. Br. Med. Bull., 1994, 50(2), 272-298.
Mancia, G.; De Backer, G.; Dominiczak, A.; Cifkova, R.; Fagard, R.; Germano, G.; Grassi, G.; Heagerty, A.M.; Kjeldsen, S.E.; Laurent, S.; Narkiewicz, K.; Ruilope, L.; Rynkiewicz, A.; Schmieder, R.E.; Boudier, H.A.; Zanchetti, A.; Vahanian, A.; Camm, J.; De Caterina, R.; Dean, V.; Dickstein, K.; Filippatos, G.; Funck-Brentano, C.; Hellemans, I.; Kristensen, S.D.; McGregor, K.; Sechtem, U.; Silber, S.; Tendera, M.; Widimsky, P.; Zamorano, J.L.; Erdine, S.; Kiowski, W.; Agabiti-Rosei, E.; Ambrosioni, E.; Lindholm, L.H.; Viigimaa, M.; Adamopoulos, S.; Agabiti-Rosei, E.; Ambrosioni, E.; Bertomeu, V.; Clement, D.; Erdine, S.; Farsang, C.; Gaita, D.; Lip, G.; Mallion, J.M.; Manolis, A.J.; Nilsson, P.M.; O’Brien, E.; Ponikowski, P.; Redon, J.; Ruschitzka, F.; Tamargo, J.; van Zwieten, P.; Waeber, B.; Williams, B. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens., 2007, 25(6), 1105-1187.
Page, I.H. The mosaic theory 32 years later. Hypertension, 1982, 4(2), 177.
Frohlich, E.D. The first Irvine H. Page lecture. The mosaic of hypertension: past, present and future. 1988. J. Hypertens. Suppl., 1988, 6(4), S2-S11.
Fung, V.; Huang, J.; Brand, R.; Newhouse, J.P.; Hsu, J. Hypertension treatment in a medicare population: adherence and systolic blood pressure control. Clin. Ther., 2007, 29(5), 972-984.
Corrao, G.; Parodi, A.; Nicotra, F.; Zambon, A.; Merlino, L.; Cesana, G.; Mancia, G. Better compliance to antihypertensive medications reduces cardiovascular risk. J. Hypertens., 2011, 29(3), 610-618.
Curb, J.D.; Schneider, K.; Taylor, J.O.; Maxwell, M.; Shulman, N. Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program. Hypertension, 1988, 11(3 Pt 2), Ii51-Ii55.
Bardage, C.; Isacson, D.G. Self-reported side-effects of antihypertensive drugs: an epidemiological study on prevalence and impact on health-state utility. Blood Press., 2000, 9(6), 328-334.
Vawter, L.; Tong, X.; Gemilyan, M.; Yoon, P.W. Barriers to antihypertensive medication adherence among adults--United States, 2005. J. Clin. Hypertens, 2008, (Greenwich). 10(12), 922-929.
Martin, M.Y.; Kohler, C.; Kim, Y.I.; Kratt, P.; Schoenberger, Y.M.; Litaker, M.S.; Prayor-Patterson, H.M.; Clarke, S.J.; Andrews, S.; Pisu, M. Taking less than prescribed: medication nonadherence and provider-patient relationships in lower-income, rural minority adults with hypertension. J. Clin. Hypertens. (Greenwich), 2010, 12(9), 706-713.
Benson, J.; Britten, N. Patients’ views about taking antihypertensive drugs: questionnaire study. BMJ, 2003, 326(7402), 1314-1315.
AlGhurair, S.A.; Hughes, C.A.; Simpson, S.H.; Guirguis, L.M. A systematic review of patient self-reported barriers of adherence to antihypertensive medications using the world health organization multidimensional adherence model. J. Clin. Hypertens. (Greenwich), 2012, 14(12), 877-886.
Wiysonge, C.S.; Bradley, H.A.; Volmink, J.; Mayosi, B.M.; Mbewu, A.; Opie, L.H. Beta-blockers for hypertension. Cochrane Database Syst. Rev., 2012, 11d002003
Corrao, G.; Zambon, A.; Parodi, A.; Poluzzi, E.; Baldi, I.; Merlino, L.; Cesana, G.; Mancia, G. (2008).Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population-based study in Italy. J. Hypertens., 26(4), 819-824.
Ross, S.D.; Akhras, K.S.; Zhang, S.; Rozinsky, M.; Nalysnyk, L. Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis. Pharmacotherapy, 2001, 21(8), 940-953.
Kotseva, K.; Wood, D.; De Bacquer, D.; De Backer, G.; Rydén, L.; Jennings, C.; Gyberg, V.; Amouyel, P.; Bruthans, J.; Castro Conde, A.; Cífková, R.; Deckers, J.W.; De Sutter, J.; Dilic, M.; Dolzhenko, M.; Erglis, A.; Fras, Z.; Gaita, D.; Gotcheva, N.; Goudevenos, J.; Heuschmann, P.; Laucevicius, A.; Lehto, S.; Lovic, D.; Miličić, D.; Moore, D.; Nicolaides, E.; Oganov, R.; Pajak, A.; Pogosova, N.; Reiner, Z.; Stagmo, M.; Störk, S.; Tokgözoğlu, L.; Vulic, D. ; on behalf of the EUROASPIRE al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur. J. Prev. Cardiol., 2015.
Nwankwo, T.; Yoon, S.S.; Burt, V.; Gu, Q. Hypertension among adults in the United States: National Health and Nutrition Examination Survey, 2011-2012. NCHS Data Brief, 133. 2013, 1-8.
Gu, Q.; Burt, V.L.; Dillon, C.F.; Yoon, S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health And Nutrition Examination Survey, 2001 to 2010. Circulation, 2012, 126(17), 2105-2114.
Wolf-Maier, K.; Cooper, R.S.; Kramer, H.; Banegas, J.R.; Giampaoli, S.; Joffres, M.R.; Poulter, N.; Primatesta, P.; Stegmayr, B.; Thamm, M. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension, 2004, 43(1), 10-17.
Wolf-Maier, K.; Cooper, R.S.; Banegas, J.R.; Giampaoli, S.; Hense, H.W.; Joffres, M.; Kastarinen, M.; Poulter, N.; Primatesta, P.; Rodriguez-Artalejo, F.; Stegmayr, B.; Thamm, M.; Tuomilehto, J.; Vanuzzo, D.; Vescio, F. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA, 2003, 289(18), 2363-2369.
Kearney, P.M.; Whelton, M.; Reynolds, K.; Whelton, P.K.; He, J. Worldwide prevalence of hypertension: a systematic review. J. Hypertens., 2004, 22(1), 11-19.
Bramlage, P.; Bohm, M.; Volpe, M.; Khan, B.V.; Paar, W.D.; Tebbe, U.; Thoenes, M. A global perspective on blood pressure treatment and control in a referred cohort of hypertensive patients. J. Clin. Hypertens. (Greenwich), 2010, 12(9), 666-677.
Fagard, R.H. Resistant hypertension. Heart, 2012, 98(3), 254-261.
Persell, S.D. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension, 2011, 57(6), 1076-1080.
Daugherty, S.L.; Powers, J.D.; Magid, D.J.; Tavel, H.M.; Masoudi, F.A.; Margolis, K.L.; O’Connor, P.J.; Selby, J.V.; Ho, P.M. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation, 2012, 125(13), 1635-1642.
Marcus, J.A.; Pothineni, A.; Marcus, C.Z.; Bisognano, J.D. The role of obesity and obstructive sleep apnea in the pathogenesis and treatment of resistant hypertension. Curr. Hypertens. Rep., 2014, 16(1), 411.
Shimosawa, T. Salt, the renin-angiotensin-aldosterone system and resistant hypertension. Hypertens. Res., 2013, 36(8), 657-660.
Pabuccu, T.; Baris, N.; Ozpelit, E.; Akdeniz, B.; Guneri, S. The relationship between resistant hypertension and arterial stiffness. Clin. Exp. Hypertens., 2012, 34(1), 57-62.
Ho, P.; Magid, D.J.; Shetterly, S.M.; Olson, K.L.; Peterson, P.N.; Masoudi, F.A.; Rumsfeld, J.S. IMportance of therapy intensification and medication nonadherence for blood pressure control in patients with coronary disease. Arch. Intern. Med., 168(3), 271-276.
de la Sierra, A.; Segura, J.; Banegas, J.R.; Gorostidi, M.; de la Cruz, J.J.; Armario, P.; Oliveras, A.; Ruilope, L.M. Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring. Hypertension, 2011, 57(5), 898-902.
Nishizaka, M.K.; Zaman, M.A.; Calhoun, D.A. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am. J. Hypertens., 2003, 16(11 Pt 1), 925-930.
Scheffers, I.J.; Kroon, A.A.; Schmidli, J.; Jordan, J.; Tordoir, J.J.; Mohaupt, M.G.; Luft, F.C.; Haller, H.; Menne, J.; Engeli, S.; Ceral, J.; Eckert, S.; Erglis, A.; Narkiewicz, K.; Philipp, T.; de Leeuw, P.W. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J. Am. Coll. Cardiol., 56(15), 1254-1258.
Schlaich, M.P.; Krum, H.; Sobotka, P.A.; Esler, M.D. Renal denervation and hypertension. Am. J. Hypertens., 2011, 24(6), 635-642.
Williams, B.; MacDonald, T.M.; Morant, S.; Webb, D.J.; Sever, P.; McInnes, G.; Ford, I.; Cruickshank, J.K.; Caulfield, M.J.; Salsbury, J.; Mackenzie, I.; Padmanabhan, S.; Brown, M.J. British Hypertension Society's PATHWAY Studies Group.Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet, 2015, 386(10008), 2059-2068.
Paulis, L.; Rajkovicova, R.; Simko, F. New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon? Curr. Hypertens. Rep., 2015, 17(6), 557.
Packer, M.; Califf, R.M.; Konstam, M.A.; Krum, H.; McMurray, J.J.; Rouleau, J.L.; Swedberg, K. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation, 2002, 106(8), 920-926.
Norton, G.R.; Woodiwiss, A.J.; Hartford, C.; Trifunovic, B.; Middlemost, S.; Lee, A.; Allen, M.J. (1999).Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects. Am. J. Hypertens., 12(6), 563-571.
Bhatt, D.L.; Kandzari, D.E.; O’Neill, W.W.; D’Agostino, R.; Flack, J.M.; Katzen, B.T.; Leon, M.B.; Liu, M.; Mauri, L.; Negoita, M.; Cohen, S.A.; Oparil, S.; Rocha-Singh, K.; Townsend, R.R.; Bakris, G.L. A Controlled Trial of Renal Denervation for Resistant Hypertension. N. Engl. J. Med., 2014.
Rossi, G.P.; Seccia, T.M.; Maniero, C.; Pessina, A.C. (2011). Drug-related hypertension and resistance to antihypertensive treatment: a call for action. J. Hypertens., 29(12), 2295-2309.
Bonn, D. Adverse drug reactions remain a major cause of death. Lancet, 1998, 351(9110), 1183.
Lazarou, J.; Pomeranz, B.H.; Corey, P.N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA, 1998, 279(15), 1200-1205.
Hakkarainen, K.M.; Hedna, K.; Petzold, M.; Hagg, S. Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions--a meta-analysis. PLoS One, 2012, 7(3)e33236
Edwards, I.R.; Aronson, J.K. Adverse drug reactions: definitions, diagnosis, and management. Lancet, 2000, 356(9237), 1255-1259.
Goodman & Gilman’s the pharmacological basis of therapeutics; New York: McGraw-Hill, 2001.
Fulton, M.M.; Allen, E.R. Polypharmacy in the elderly: a literature review. J. Am. Acad. Nurse Pract., 2005, 17(4), 123-132.
Hajjar, E.R.; Cafiero, A.C.; Hanlon, J.T. Polypharmacy in elderly patients. Am. J. Geriatr. Pharmacother., 2007, 5(4), 345-351.
Center, S.E. Pattern of Medication Use in the United States Boston: Boston University; 2006. Available at: research/studies/slone-survey [accessed 2014 April 4, 2014].
Fialova, D.; Topinkova, E.; Gambassi, G.; Finne-Soveri, H.; Jonsson, P.V.; Carpenter, I.; Schroll, M.; Onder, G.; Sorbye, L.W.; Wagner, C.; Reissigova, J.; Bernabei, R. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA, 2005, 293(11), 1348-1358.
Hanlon, J.T.; Schmader, K.E.; Koronkowski, M.J.; Weinberger, M.; Landsman, P.B.; Samsa, G.P.; Lewis, I.K. Adverse drug events in high risk older outpatients. J. Am. Geriatr. Soc., 1997, 45(8), 945-948.
Butt, T.F.; Branch, R.L.; Beesley, L.; Martin, U. Managing hypertension in the very elderly: effect of adverse drug reactions (ADRs) on achieving targets. J. Hum. Hypertens., 2010, 24(8), 514-518.
White, W.B. Defining the problem of treating the patient with hypertension and arthritis pain. Am. J. Med., 122(5)2009. , S3-S9.
Pavlicevic, I.; Kuzmanic, M.; Rumboldt, M.; Rumboldt, Z. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can. J. Clin. Pharmacol., 2008, 15(3), e372-e382.
Johnson, A.G.; Nguyen, T.V.; Day, R.O. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann. Intern. Med., 1994, 121(4), 289-300.
ISTAT. Persone con Presenza di alcune Malattie Croniche Rome: ISTAT; 2013. Available at: [accessed 2014 April 4, 2014].
Meune, C.; Mourad, J.J.; Bergmann, J.F.; Spaulding, C. Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance. J. Renin Angiotensin Aldosterone Syst., 2003, 4(3), 149-154.
Gyamlani, G.; Geraci, S.A. Secondary hypertension due to drugs and toxins. South Med. J., 100(7)2007. , 692-699. quiz 700, 708.
Grossman, E.; Messerli, F.H. Drug-induced hypertension: an unappreciated cause of secondary hypertension. Am. J. Med., 2012, 125(1), 14-22.
Hammer, F.; Stewart, P.M. Cortisol metabolism in hypertension. Best Pract. Res. Clin. Endocrinol. Metab., 2006, 20(3), 337-353.
Funder, J.W. Aldosterone, mineralocorticoid receptors and vascular inflammation. Mol. Cell. Endocrinol., 2004, 217(1-2), 263-269.
Rickard, A.J.; Funder, J.W.; Morgan, J.; Fuller, P.J.; Young, M.J. Does glucocorticoid receptor blockade exacerbate tissue damage after mineralocorticoid/salt administration? Endocrinology, 2007, 148(10), 4829-4835.
Tangredi, J.F.; Buxton, I.L. Hypertension as a complication of topical testosterone therapy. Ann. Pharmacother., 2001, 35(10), 1205-1207.
Wilson, A.M.; Blumsohn, A.; Jung, R.T.; Lipworth, B.J. Asthma and Cushing’s syndrome. Chest, 2000, 117(2), 593-594.
Short, P.M.; Lipworth, S.I.; Elder, D.H.; Schembri, S.; Lipworth, B.J. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ, 2011, 342, d2549.
Rutten, F.H.; Zuithoff, N.P.; Hak, E.; Grobbee, D.E.; Hoes, A.W. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch. Intern. Med., 2010, 170(10), 880-887.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2015
Published on: 19 January, 2016
Page: [210 - 223]
Pages: 14
DOI: 10.2174/1871529X16666160101122820
Price: $65

Article Metrics

PDF: 74