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Blood Pressure Responses to Noncardiovascular Drugs in Development and Therapeutic Use

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Cardiovascular Safety in Drug Development and Therapeutic Use

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Abstract

This chapter focuses on unintended drug-induced blood pressure responses. While both increases and decreases are legitimate areas of investigation (Kane-Gill et al. 2014; Kennelly and Esaian 2013), our attention falls on increases. As was noted in Sect. 3.4.4, high blood pressure is authoritative regarded as the greatest threat to the global burden of disease (Horton 2013; Das and Samarasekera 2013; Lim et al. 2013). As hypertension has been studied across several decades, we have learned that there are multiple ways in which increased blood pressure may occur (see Frohlich 1977; Page 1982; Dustan 1990; Harrison 2013). It has now also become clear that noncardiovascular drugs can lead to off-target increases in blood pressure and can also do so via a variety of mechanisms of action. As Grossman and Messerli (2012) observed, “Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower BP may paradoxically increase BP, or an increase in pressure may be encountered after their discontinuation.”

A variety of therapeutic agents or chemical substances may increase blood pressure… When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent (Grossman et al. 2015).

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References

  • Authier S, Pugsley MK, Curtis MJ (2015) Haemodynamic assessment in safety pharmacology. In: Pugsley MK, Curtis MJ (eds) Principles of safety pharmacology: handbook of experimental pharmacology 229. Springer, Berlin, pp 221–241

    Chapter  Google Scholar 

  • Authier S, Tanguay JF, Fournier S et al (2008) Conscious and anesthetized non-human primate safety pharmacology models: hemodynamic sensitivity comparison. J Pharmacol Toxicol Methods 58:94–98

    Article  CAS  PubMed  Google Scholar 

  • Bhide AA, Digesu GA, Fernando R et al (2012) Use of mirabegron in treating overactive bladder. Int Urogynecol J 23:1345–1348

    Article  PubMed  Google Scholar 

  • Das P, Samarasekera U (2013) The story of GBD 2010: a “super-human” effort. Lancet 380:2067–2070

    Article  Google Scholar 

  • Dustan HP (1990) Irvine Page lecture. Legacies of Irvine H. Page. J Hypertens Suppl 8:S29–S34

    CAS  PubMed  Google Scholar 

  • Franklin SS, Thijs L, Hansen TW et al (2013) White-coat hypertension: new insights from recent studies. Hypertension 62:982–987

    Article  CAS  PubMed  Google Scholar 

  • Frohlich ED (1977) Essential hypertension. Pathophysiological mechanisms and therapy. Arch Intern Med 137:772–775

    Article  CAS  PubMed  Google Scholar 

  • Grossman E, Messerli FH (2012) Drug-induced hypertension: an unappreciated cause of secondary hypertension. Am J Med 125:14–22

    Article  CAS  PubMed  Google Scholar 

  • Grossman A, Messerli FH, Grossman E (2015) Drug induced hypertension: an unappreciated cause of secondary hypertension. Eur J Pharmacol 763:15–22

    Article  CAS  PubMed  Google Scholar 

  • Harrison DG (2013) The mosaic theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension. J Am Soc Hypertens 7:68–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horton R (2013) GBD 2010: understanding disease, injury, and risk. Lancet 380:2053–2054

    Article  Google Scholar 

  • Kane-Gill SL, LeBlanc JM, Dasta JF, Devabhakthuni S, Critical Care Pharmacotherapy Trials Network (2014) A multicenter study of the point prevalence of drug-induced hypotension in the ICU. Crit Care Med 42:2197–2203

    Article  CAS  PubMed  Google Scholar 

  • Kennelly C, Esaian D (2013) Drug-induced cardiovascular adverse events in the intensive care unit. Crit Care Nurs Q 36:323–334

    Article  PubMed  Google Scholar 

  • Krakoff LR (2006) Cost-effectiveness of ambulatory blood pressure: a reanalysis. Hypertension 47:29–34

    Article  CAS  PubMed  Google Scholar 

  • Lim SS, Vos T, Flaxman AD et al (2013) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2224–2260

    Article  Google Scholar 

  • Lovibond K, Jowett S, Barton P et al (2011) Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modeling study. Lancet 378:1219–1230

    Article  PubMed  Google Scholar 

  • NICE (National Institute for Health and Care Excellence) (2011) Clinical guideline 127. Hypertension: clinical management of primary hypertension in adults. August 2011. Available at: http://www.nice.org.uk/guidance/CG127 Accessed 27 Nov 2015

  • O’Brien E (2011a) The value of 24-hour blood pressure monitoring to assess the efficacy of antihypertensive drug treatment. Hot Topics Hypertens 4:7–23

    Google Scholar 

  • O’Brien E (2011b) 24-hour ambulatory blood pressure measurement in clinical practice and research: a critical review of a technique in need of implementation. J Intern Med 269:478–495

    Article  PubMed  Google Scholar 

  • O’Brien E (2012) First Thomas Pickering memorial lecture ambulatory blood pressure measurement is essential for the management of hypertension. J Clin Hypertens (Greenwich) 14:836–847

    Article  Google Scholar 

  • O’Brien E, Turner JR (2013) Assessing blood pressure responses to noncardiovascular drugs: the beneficial role of ambulatory blood pressure monitoring. J Clin Hypertens (Greenwich) 15:55–62

    Article  Google Scholar 

  • Page IH (1982) The mosaic theory 32 years later. Hypertension 4:177

    Article  CAS  PubMed  Google Scholar 

  • Pickering TG, James GD, Boddie C et al (1988) How common is white coat hypertension? JAMA 259:225–228

    Article  CAS  PubMed  Google Scholar 

  • Sager P, Heilbraun J, Turner JR et al (2013) Assessment of drug-induced increases in blood pressure during drug development: report from the Cardiac Safety Research Consortium. Am Heart J 165:477–488

    Article  PubMed  Google Scholar 

  • Siu AL, U.S. Preventive Services Task Force (2015) Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 163:778–786

    Article  PubMed  Google Scholar 

  • Stockbridge S (2011) Letter to the editor: ABPM part of FDA reviews. Drug Inf J 45:567

    Article  Google Scholar 

  • Svensson P, de Faire U, Sleight P et al (2001) Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension 38:E28–E32

    Article  CAS  PubMed  Google Scholar 

  • Virdis A, Ghiadoni L, Taddei S, Italian Society of Hypertension (SIIA) (2014) Clinical management of drug-induced hypertension: 2013 practical recommendations of the Italian Society of Hypertension (SIIA). High Blood Press Cardiovasc Prev 21:77–79

    Article  CAS  PubMed  Google Scholar 

  • Williams B (2000) The renin-angiotensin system and cardiovascular disease: hope or hype? J Renin Angiotensin Aldosterone Syst 1:142–146

    Article  CAS  PubMed  Google Scholar 

  • Yusuf S, Sleight P, Pogue J et al (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:145–153

    Article  CAS  PubMed  Google Scholar 

Further Reading

  • Albrecht M, Henke J, Tacke S, Markert M, Guth B (2014) Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats. BMC Vet Res 10:198

    Article  PubMed  PubMed Central  Google Scholar 

  • Amouzadeh HR, Engwall MJ, Vargas HM (2015) Safety pharmacology evaluation of biopharmaceuticals. Handb Exp Pharmacol 229:385–404

    Article  PubMed  Google Scholar 

  • Barter PJ, Caulfield M, Eriksson M et al (2007) Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 357:2109–2122

    Article  CAS  PubMed  Google Scholar 

  • Bhatt S, Foote S, Smith A, Butler P, Steidl-Nichols J (2015) A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: preclinical correlate to a clinical test. J Pharmacol Toxicol Methods 73:49–55

    Article  CAS  PubMed  Google Scholar 

  • Blankfield RP (2012) Blood pressure, fluid retention and the cardiovascular risk of drugs. Future Cardiol 8:489–493

    Article  CAS  PubMed  Google Scholar 

  • Breaux-Shropshire TL, Judd E, Vucovich LA, Shropshire TS, Singh S (2015) Does home blood pressure monitoring improve patient outcomes? A systematic review comparing home and ambulatory blood pressure monitoring on blood pressure control and patient outcomes. Integr Blood Press Control 8:43–49

    Article  PubMed  PubMed Central  Google Scholar 

  • Campbell NR, Gelfer M, Stergiou GS et al (2016) A call to regulate manufacture and marketing of blood pressure devices and cuffs: a position statement from the World Hypertension League, International Society of Hypertension and Supporting Hypertension Organizations. J Clin Hypertens (Greenwich) 18:378–380

    Google Scholar 

  • Caruso A, Frances N, Meille C et al (2014) Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: methods and examples in drug development. J Pharmacol Toxicol Methods 70:73–85

    Article  CAS  PubMed  Google Scholar 

  • Choi HY, Park HC, Ha SK (2015) Salt sensitivity and hypertension: a paradigm shift from kidney malfunction to vascular endothelial dysfunction. Electrolyte Blood Press 13:7–16

    Article  PubMed  PubMed Central  Google Scholar 

  • Choure BK, Gosavi D, Nanotkar S (2014) Comparative cardiovascular safety of risperidone and olanzapine, based on electrocardiographic parameters and blood pressure: a prospective open label observational study. Indian J Pharmacol 46:493–497

    Article  PubMed  PubMed Central  Google Scholar 

  • Collins TA, Bergenholm L, Abdulla T et al (2015) Modeling and simulation approaches for cardiovascular function and their role in safety assessment. CPT Pharmacometrics Syst Pharmacol 4:e00018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daskalopoulou SS, Rabi DM, Zarnke KB, Canadian Hypertension Education Program et al (2015) The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 31:549–568

    Article  PubMed  Google Scholar 

  • Dolan E, O’Brien E (2015) Is it daily, monthly, or yearly blood pressure variability that enhances cardiovascular risk? Curr Cardiol Rep 17:93

    Article  PubMed  Google Scholar 

  • Draman MS, Dolan E, van der Poel L et al (2015) The importance of night-time systolic blood pressure in diabetic patients: Dublin Outcome Study. J Hypertens 33:1373–1377

    Article  CAS  PubMed  Google Scholar 

  • Eghbalibabadi M, Ashouri E (2014) Comparison of the effects of two teaching methods on the nursing students’ performance in measurement of blood pressure. Iran J Nurs Midwifery Res 19:381–384

    PubMed  PubMed Central  Google Scholar 

  • Egner B (2015) High definition oscillometry: non-invasive blood pressure measurement and pulse wave analysis. Handb Exp Pharmacol 229:243–264

    Article  PubMed  Google Scholar 

  • Ewart L, Aylott M, Deurinck M et al (2014) The concordance between nonclinical and phase I clinical cardiovascular assessment from a cross-company data sharing initiative. Toxicol Sci 142:427–435

    Article  CAS  PubMed  Google Scholar 

  • Gazibara T, Rancic B, Maric G et al (2015) Medical students, do you know how to measure blood pressure correctly? Blood Press Monit 20:27–31

    Article  PubMed  Google Scholar 

  • Gintant G (2015) In vitro early safety pharmacology screening: perspectives related to cardiovascular safety. Handb Exp Pharmacol 229:47–64

    Article  PubMed  Google Scholar 

  • Grassi G, Mark A, Esler M (2015) The sympathetic nervous system alterations in human hypertension. Circ Res 116:976–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall JE, do Carmo JM, Da Silva AA, Wang Z, Hall ME (2015) Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res 116:991–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harvey A, Montezano AC, Touyz RM (2015) Vascular biology of ageing: implications in hypertension. J Mol Cell Cardiol 83:112–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imai Y (2014) Clinical significance of home blood pressure and its possible practical application. Clin Exp Nephrol 18:24–40

    Article  PubMed  Google Scholar 

  • Imai Y, Obara T, Asamaya K, Ohkubo T (2013) The reason why home blood pressure measurements are preferred over clinic or ambulatory blood pressure in Japan. Hypertens Res 36:661–672

    Article  PubMed  Google Scholar 

  • Imai Y, Hosaka M, Elnagar N, Satoh M (2014) Clinical significance of home blood pressure measurements for the prevention and management of high blood pressure. Clin Exp Pharmacol Physiol 41:37–45

    Article  CAS  PubMed  Google Scholar 

  • Johns DG, Duffy J, Fisher T, Hubbard BK, Forrest MJ (2012) On- and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors. Drugs 72:491–507

    Article  CAS  PubMed  Google Scholar 

  • Juhanoja E, Niiranen TJ, Johansson JK, Puukka PJ, Jula AM (2015) Agreement between ambulatory, home and office blood pressure variability. J Hypertens 33(Suppl 1):e42–e43

    Article  PubMed  Google Scholar 

  • Kang YY, Li Y, Huang QF et al (2015) Accuracy of home versus ambulatory blood pressure monitoring in the diagnosis of white-coat and masked hypertension. J Hypertens 33:1580–1587

    Article  CAS  PubMed  Google Scholar 

  • Kassel LE, Odum LE (2015) Our own worst enemy: pharmacologic mechanisms of hypertension. Adv Chronic Kidney Dis 22:245–252

    Article  PubMed  Google Scholar 

  • Kjeldsen SE, Aksnes TA, Ruilope LM (2014) Clinical implications of the 2013 ESH/ESC hypertension guidelines: targets, choice of therapy, and blood pressure monitoring. Drugs R D 14:31–43

    Article  PubMed  PubMed Central  Google Scholar 

  • Kjeldsen S, Feldman RD, Lisheng L et al (2014) Updated national and international hypertension guidelines: a review of current recommendations. Drugs 74:2033–2051

    Article  PubMed  PubMed Central  Google Scholar 

  • Klein SK, Redfern WS (2015) Cardiovascular safety risk assessment for new candidate drugs from functional and pathological data: conference report. J Pharmacol Toxicol Methods 76:1–6

    Article  CAS  PubMed  Google Scholar 

  • Kremer JJ, Bills AJ, Hanke NJ et al (2015) Evaluation of cardiovascular changes in dogs administered three positive controls using jacketed external telemetry-blood pressure (JET-BP). J Pharmacol Toxicol Methods 75:27–37, May 20

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Chee Y, Kim I et al (2015) High-fidelity digital recording and playback sphygmomanometry system: device description and proof of concept. Blood Press Monit 20:266–272

    Article  PubMed  Google Scholar 

  • Martel E, Egner B, Brown SA et al (2013) Comparison of high-definition oscillometry, a non-invasive technology for arterial blood pressure measurement, with a direct invasive method using radio-telemetry in awake healthy cats. J Feline Med Surg 15:1104–1113

    Article  PubMed  Google Scholar 

  • McKee J, Daller J, Baumgartner B, Pettinger S (2014) Evaluation of the sensitivity of a new fully implantable telemetry device and the importance of simultaneously measuring cardiac output and left ventricular pressure. J Pharmacol Toxicol Methods 69:229–236

    Article  CAS  PubMed  Google Scholar 

  • Mounier-Vehier C, Boudghène F, Claisse G, Delsart P (2015) Iatrogenic and drug-induced hypertension. Rev Prat 65:809–816

    PubMed  Google Scholar 

  • Nishimoto M, Fujita T (2015) Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways. Am J Physiol Renal Physiol 308:F377–F387

    Article  CAS  PubMed  Google Scholar 

  • O’Brien E (2016) Why is it that we continue to deny patients ambulatory blood pressure monitoring? Hypertension 67:484–487

    PubMed  Google Scholar 

  • O’Brien E (2016) Prognostic value of ambulatory blood pressure monitoring in obese patients. J Clin Hypertens (Greenwich) 18:119–120

    Article  Google Scholar 

  • O’Brien E (2016) Why is it so difficult to influence the clinical management of hypertension? J Clin Hypertens (Greenwich) [Epub ahead of print]

    Google Scholar 

  • O’Brien E, Dolan E, Atkins N (2015) Failure to provide ABPM to all hypertensive patients amounts to medical ineptitude. J Clin Hypertens (Greenwich) 17:462–465

    Article  Google Scholar 

  • Omboni S, Palatini P, Parati G, Working Group on Blood Pressure Monitoring of the Italian Society of Hypertension (2015) Standards for ambulatory blood pressure monitoring clinical reporting in daily practice: recommendations from the Italian Society of Hypertension. Blood Press Monit 20:241–244

    Article  PubMed  Google Scholar 

  • Paolasso JA, Crespo F, Arias V et al (2015) Clinical practice of ambulatory versus home blood pressure monitoring in hypertensive patients. Blood Press Monit 20:241–244

    Article  Google Scholar 

  • Parati G, Stergiou G, O’Brien E, European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability et al (2014) European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens 32:1359–1366

    Article  CAS  PubMed  Google Scholar 

  • Rader DJ (2007) Illuminating HDL: is it still a viable therapeutic target? N Engl J Med 357:2180–2183

    Article  CAS  PubMed  Google Scholar 

  • Ray EC, Rondon-Berrios H, Boyd CR, Kleyman TR (2015) Sodium retention and volume expansion in nephrotic syndrome: implications for hypertension. Adv Chronic Kidney Dis 22:179–184

    Article  PubMed  PubMed Central  Google Scholar 

  • Rysnik MK, Cripps P, Iff I (2013) A clinical comparison between a non-invasive blood pressure monitor using high definition oscillometry (Memodiagnostic MD 15/90 Pro) and invasive arterial blood pressure measurement in anaesthetized dogs. Vet Anaesth Analg 40:503–511

    Article  PubMed  Google Scholar 

  • Sarazan RD (2014) Cardiovascular pressure measurement in safety assessment studies: technology requirements and potential errors. J Pharmacol Toxicol Methods 70:210–223

    Article  CAS  PubMed  Google Scholar 

  • Segal L, Roger V, Williams C, Destexhe E, Garçon N (2015) Effects of adjuvant systems on the cardiovascular and respiratory functions in telemetered conscious dogs and anaesthetised rats. Regul Toxicol Pharmacol 73:116–125

    Article  CAS  PubMed  Google Scholar 

  • Stephan D, Gaertner S, Cordeanu EM (2015) A critical appraisal of the guidelines from France, the UK, Europe and the USA for the management of hypertension in adults. Arch Cardiovasc Dis 108:453–459

    Article  PubMed  Google Scholar 

  • Stergiou GS, Ntineri A (2015) The optimal schedule for self-home blood pressure monitoring. J Hypertens 33:693–697

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga J, Takamura N, Ogata K et al (2014) An advanced objective structured clinical examination using patient simulators to evaluate pharmacy students’ skills in physical assessment. Am J Pharm Educ 78:184

    Article  PubMed  PubMed Central  Google Scholar 

  • Viera AJ, Lin FC, Tuttle LA et al (2014) Reproducibility of masked hypertension among adults 30 years or older. Blood Press Monit 19:208–215

    Article  PubMed  PubMed Central  Google Scholar 

  • Viera AJ, Tuttle LA, Voora R, Olsson E (2015) Comparison of patients’ confidence in office, ambulatory, and home blood pressure measurements as methods of assessing for hypertension. Blood Press Monit 20:335–340

    Article  PubMed  PubMed Central  Google Scholar 

  • Viera AJ, Tuttle L, Zeng J (2016) Dollars and discomfort: what will people be willing to give for better blood pressure assessment? J Clin Hypertens (Greenwich) 18:422–423

    Google Scholar 

  • Virdis A, Ghiadoni L, Taddei S, Italian Society of Hypertension (SIIA) (2014) Clinical management of drug-induced hypertension: 2013 Practical Recommendations of the Italian Society of Hypertension (SIIA). High Blood Press Cardiovasc Prev 21:77–79

    Article  CAS  PubMed  Google Scholar 

  • Weber MA, Schiffrin EL, White WB et al (2014) Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) 16:14–26

    Article  Google Scholar 

  • Weber MA, Turner JR (2016) Ambulatory blood pressure monitoring: new directions and uncertainties arise from the United States Preventive Services Task Force recommendation on the diagnosis of hypertension. J Clin Hypertens (Greenwich) 18:173–175

    Google Scholar 

  • Yuan H, Zhao J, Guo J (2014) Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies. J Pharmacol Toxicol Methods 70:19–28

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Cardiac Safety Services Quintiles, Durham, North Carolina, USA

    J. Rick Turner (Chief Scientific Advisor)

  2. Research Team, Cardiac Safety Services Quintiles, Mumbai, India

    Dilip R. Karnad (Head)

  3. Cardiac Safety Services Global Head, Cardiac Safety Center of Excellence Quintiles, Mumbai, India

    Snehal Kothari (Chief Medical & Scientific Officer)

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Turner, J.R., Karnad, D.R., Kothari, S. (2017). Blood Pressure Responses to Noncardiovascular Drugs in Development and Therapeutic Use. In: Cardiovascular Safety in Drug Development and Therapeutic Use. Adis, Cham. https://doi.org/10.1007/978-3-319-40347-2_11

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