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Adverse Reactions to Antihypertensive Therapy

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Abstract

A large number of antihypertensive agents are available today. They belong to different drug classes and permit the treating physician to choose the drug he deems best suited for the treatment of an individual patient. Because hypertension is usually asymptomatic yet requires long-term therapy, consideration of potential undesirable effects of drugs used for its treatment is important for making the appropriate choice. In this context, a precise understanding of the typical adverse reaction profiles of the different drugs is essential. This article provides a short review of the adverse reaction profiles of the main classes of antihypertensive drugs and refers to topics such as the recent controversy regarding calcium channel blockers and comparative investigations between different antihypertensive agents. Furthermore, the effects of antihypertensives on metabolic parameters, differences between their effects in subgroups of patients and in patients with different concomitant diseases, and the potential of antihypertensives for interactions with other drugs are briefly discussed. Even with a good knowledge of all of these aspects, however, no fixed plan for drug treatment of hypertension suitable for every patient can be established. A high percentage of adverse drug reactions can, however, be avoided by appropriate drug selection and dosage, carried out after careful consideration of the known adverse reaction profiles as well as the known spectrum of pharmacological actions of the different compounds. Low doses are often effective and well tolerated. Instead of increasing the dose, it is usually preferable to add a low dose of a second agent with a different mode of action if one drug given alone does not sufficiently lower blood pressure. This procedure avoids many adverse drug reactions attributable to an exaggerated pharmacological response, and, if chosen carefully, this combination may also reduce counterregulatory reactions secondary to the fall in blood pressure.

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References

  1. Opie LH. Choosing the correct drug for the individual hypertensive patient. Drugs 1992;44:147-155.

    Google Scholar 

  2. Aellig WH. Antihypertensive drugs - adverse reaction profiles. Abstracts of the 6th International Congress of Cardiovascular Pharmacotherapy, Sydney, Australia, 1996:36.

  3. Dukes MNG, ed. Meyler's Side Effects of Drugs. Amsterdam: Elsevier, 1992.

    Google Scholar 

  4. Prichard BN, Owens CW, Woolf AS. Adverse reactions to diuretics. Eur Heart J 1992;13(Suppl. G):96-103.

    Google Scholar 

  5. Grobbe DE, Hoes AW. Non-potassium-sparing diuretics and risk of sudden cardiac death. J Hypertens 1995;13: 1539-1545.

    Google Scholar 

  6. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995;274:620-625.

    Google Scholar 

  7. Furberg CD, Psaty BM, Meyer JV. Nifedipine dose-related increase in mortality in patients with coronary heart disease Circulation 1995;92:1326-1331.

    Google Scholar 

  8. Pahor M, Guralnik JM, Cortl MC, Foley DJ, Carbonin P, Havlik RJ. Long-term survival and the use of antihypertensive medications in older persons. J Am Geriatr Soc 1995;43: 1191-1197.

    Google Scholar 

  9. Buring JE, Glynn RJ, Hennekens CH. Calcium channel blockers and myocardial infarction.A hypothesis formulated but not yet tested. JAMA 1995;274:654-655.

    Google Scholar 

  10. Opie LH, Messerli FH. Nifedipine and mortality. Grave defects in the dossier. Circulation 1995;92:1068-1073.

    Google Scholar 

  11. Aursnes I, Litleskare I, Froyland H, Abdelnoor M. Association between various drugs used for hypertension and risk of myocardial infarction. Blood Pressure 1995;4:157-163.

    Google Scholar 

  12. Hoes AW, Grobbe DE, Lubsen J, Manin't Veld AJ, van der Does E, Hofman A. Diuretics, β-blockers, and the risk for sudden cardiac death in hypertensive patients. Ann Intern Med 1995;123:481-487.

    Google Scholar 

  13. Siscovick DS, Raghunathan TE, Psaty BM, et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med 1994;330:1852-1857.

    Google Scholar 

  14. Ad hoc Subcommittee of the Liaison Committee of the World Health Organization and the International Society of Hypertension. Effects of calcium antagonists on the risk of coronary heart disease, cancer and bleeding. J Hypertens 1997;15:105-115.

    Google Scholar 

  15. DahlÖf B, Hansson L, Lindholm LH, et al. STOP-Hypertension 2: A prospective intervention trial of “newer” versus “older” treatment alternatives in old patients with hypertension. Blood Pressure 1993;2:136-141.

    Google Scholar 

  16. The Nordic Diltiazem Study (Nordil). A prospective intervention trial of calcium antagonists therapy in hypertension. Blood Pressure 1993;2:312-321.

    Google Scholar 

  17. Brown MJ, Castaigne A, Mancia G, Rosenthal T, Ruilope LM. Hypertension intervention trial in high risk patients. A comparison of the effects of nifedipine GITS and hydrochlorothiazide/amiloride on cardiovascular and cerebral morbidity and mortality (INSIGHT). Proceedings of the 7th European Meeting on Hypertension, Milan, Italy, 1995:112.

  18. Amery A, Birkenhäger W, Bulpitt CJ, et al. A multicenter trial on the treatment of isolated systolic hypertension in the elderly: Objectives, protocol, and organization. Aging 1991;3:287-302.

    Google Scholar 

  19. Hansson L. The hypertension optimal treatment study (The HOT study). Blood Pressure 1993;2:62-68.

    Google Scholar 

  20. Gong L, Zhang W, Zhu Y, et al. Shanghai Trial Of Nifedipine in the Elderly (STONE). J Hypertens 1996;14:1237-1245.

    Google Scholar 

  21. Guidelines Sub-Committee of the WHO/ISH Mild Hypertension Liaison Committee. 1993 Guidelines for the management of mild hypertension: Memorandum from a World Health Organization/International Society of Hypertension meeting. J Hypertens 1993;11:905-918.

    Google Scholar 

  22. Zanchetti A. Evaluating the benefits of an antihypertensive agent using trials based on event and organ damage: The systolic hypertension in the elderly long-term lacidipine (SHELL) trial and the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens1995;13(Suppl. 4): S35-S39.

    Google Scholar 

  23. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997;350: 757-764.

    Google Scholar 

  24. Kleinbloesem CH, van Brummelen P, Danhof M, Faber H, Urquhart J, Breimer DD. Rate of increase in the plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans. Clin Pharmacol Ther 1987;41:26-30.

    Google Scholar 

  25. Leenen FHH. 1,4-dihydropyridines versus beta-blockers for hypertension: Are either safe for the heart? Cardiovasc Drugs Ther 1996;10:397-402.

    Google Scholar 

  26. Hermans L, Bogaert M, Degaute JP, et al. Tolerability of isradipine in the treatment of mild-to-moderate hypertension in general practice: A large-scale surveillance study. J Cardiovasc Pharmacol 1992;19(Suppl. 3):S38-S45.

    Google Scholar 

  27. Silagy CA, McNeil JJ, McGrath BP. Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension. Am J Cardiol 1992;70:1299-1305.

    Google Scholar 

  28. Perry HM, Hall WD, Bartels DW, et al. Efficacy and safety of atenolol, enalapril, and isradipine in elderly hypertensive women. Am J Med 1994;96:77-86.

    Google Scholar 

  29. Vyssoulis GP, Karpanou EA, Pitsavos CE, Skoumas JN, Paleologos AA, Toutouzas PK. Differentiation of β-blocker effects on serum lipids and apolipoproteins in hypertensive patients with normolipidaemic or dyslipidaemic profiles. Eur Heart J 1992;13:1506-1513.

    Google Scholar 

  30. Paolisso G, Gambardella A, Galzerano D, Varricchio M. Insulin resistance and hypertension in the elderly. Drugs Aging 1994;4:403-409.

    Google Scholar 

  31. Suter PM, Vetter W. Metabolic effects of antihypertensive drugs. J Hypertens 1995;13(Suppl. 4):S11-S17.

    Google Scholar 

  32. Kasiske BL, Ma JZ, Kalil RSN, Louis ThA. Effects of antihypertensive therapy on serum lipids. Arch Intern Med 1995;122:133-141.

    Google Scholar 

  33. Moan A, Os I, Hjerman I, Kjeldsen SE. Hypertension therapy and risk of coronary heart disease: How do antihypertensives affect metabolic factors? Cardiology 1995;86:89-93.

    Google Scholar 

  34. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991;24:3255-3264.

    Google Scholar 

  35. DahlÖf B, Lindholm LH, Hansson L, Scherstén B, Ekbom T, Wester P-O. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991;338:1281-1285.

    Google Scholar 

  36. MRC Working Party. Medical research council trial of treatment of hypertension in older adults: Principal results. Br Med J 1992;304:405-412.

    Google Scholar 

  37. Littler WA. Nicardipine in the elderly hypertensive: A review of experience in the United Kingdom. Am Heart J 1989;117:262-265.

    Google Scholar 

  38. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men, a comparison of six antihypertensive agents with placebo. N Engl J Med 1993;328: 914-921.

    Google Scholar 

  39. Brown N J, Nadeau J H. Does race predispose to angiotensin-associated angioneurotic edema? Ann Intern Med 1993; 119:1224.

    Google Scholar 

  40. Os I, Bratland B, Dahlof B, Gisholt K, Syvertsen JO, Tretli SF. Female preponderance for lisinopril-induced cough in hypertension. Am J Hypertens 1994;7:1012-1015.

    Google Scholar 

  41. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 1992;117:234-242.

    Google Scholar 

  42. Franson KL, Kuk JM, Lam NP, Lau AH. Gender effect on diuretic response to hydrochlorothiazide and furosemide. Int J Clin Pharmacol Ther 1996;34:101-105.

    Google Scholar 

  43. Lewis CE, Grandits GA, Flack J, McDonals R, Elmer PJ. Efficacy and tolerance of antihypertensive treatment in men and women with stage 1 diastolic hypertension. Results of the treatment of mild hypertension study. Arch Intern Med 1996;156:377-385.

    Google Scholar 

  44. Straznicky NE, Louis WJ, McGrade P, Howes LG. The effects of dietary lipid modification on blood pressure, cardiovascular reactivity and sympathetic activity in man. J Hypertens 1993;11:427-437.

    Google Scholar 

  45. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echochardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322:1561-1566.

    Google Scholar 

  46. Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA 1996; 275:1507-1513.

    Google Scholar 

  47. Gottdiener JS, Reda DJ, Massie BM, et al. Effect of single drug therapy on reduction of left ventricular mass in mild to moderate hypertension: Comparison of six antihypertensive agents. Circulation 1997;95:2007-2014.

    Google Scholar 

  48. Lenert LA, Markowitz DR, Blaschke TF. Valuing of the risk of drug toxicity in therapeutic decision making. Clin Pharmacol Ther 1993;53:285-291.

    Google Scholar 

  49. Franz IW, Behr U, Ketelhut R, TÖnnesmann U. Verringerung der Antihypertonika-Dosis während Langzeitbehandlung und kompletter RÜckbildung einer linksventrikulären Hypertrophie. Dtsch Med Wschr 1996;121: 472-478.

    Google Scholar 

  50. Barnett AH. Diabetes and hypertension. Br Med Bull 1994;50:397-407.

    Google Scholar 

  51. Klauser R, Prager R, Gaube S, et al. Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus. Hypertension 1991;17:15-21.

    Google Scholar 

  52. Giordano M, Matsuda M, Sanders L, Canessa ML, DeFronzo RA. Effects of angiotensin-converting enzyme inhibitors, Ca2+ channel antagonists, and alpha-adrenergic blockers on glucose and lipid metabolism in NIDDM patients with hypertension. Diabetes 1995;44:665-671.

    Google Scholar 

  53. Prichard BN, Smith CC, Sen S, Betteridge DJ. Hypertension and insulin resistance. J Cardiovasc Pharmacol 1992; 20(Suppl. 11):S77-S84.

    Google Scholar 

  54. Herings RMC, deBoer A, Stricker BHCh, Leufkens HGM, Porsius A. Hypoglycemia associated with use of inhibitors of angiotensin converting enzyme. Lancet 1995;345:1195-1198.

    Google Scholar 

  55. Stolk RP, Hoes AW, Pols HAP, Hofman A, deJong PTVM, Lamberts SWJ, Grobbee DE. Insulin, hypertension and antihypertensive drugs in the elderly: The Rotterdam study. J Hypertens 1996;14:237-242.

    Google Scholar 

  56. Schmieder RE. Nephroprotection by antihypertensive agents. J Cardiovasc Pharmacol 1994;24(Suppl. 2):S55-S64.

    Google Scholar 

  57. Carter BL. Dosing of antihypertensive medications in patients with renal insufficiency. J Clin Pharmacol 1995;35: 81-86.

    Google Scholar 

  58. Zanchi A, Brunner HR, Waeber B, Burnier M. Renal haemodynamics and protective effects of calcium antagonists in hypertension. J Hypertens 1995;13:1363-1375.

    Google Scholar 

  59. Maki DD, MA JZ, Louis TA, Kasiske BL. Long-term effects of antihypertensive agents on proteinuria and renal function. Arch Intern Med 1995;155:1073-1080.

    Google Scholar 

  60. Maschio G, Alberti D, Janin G, et al. Angiotensin-Converting Enzyme Inhibition in Progressive Renal Insufficiency Study Group. Effects of the angiotensin converting-enzyme inhibitor benazapril on the progression of chronic renal insufficiency. N Engl J Med 1996;334:939-945.

    Google Scholar 

  61. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993;329:1456-1462.

    Google Scholar 

  62. Opie LH. Interactions with cardiovascular drugs. Curr Probl Cardiol 1993;18:531-581.

    Google Scholar 

  63. Blaufarb I, Pfeifer TM, Frishman WH. β-blockers, drug interactions of clinical significance. Drug Safety 1995;13: 359-370.

    Google Scholar 

  64. Rosenthal T, Ezra D. Calcium antagonists, drug interactions of clinical significance. Drug Safety 1995;13:157-187.

    Google Scholar 

  65. Mignat Ch, Unger T. ACE Inhibitors, drug interactions of clinical significance. Drug Safety 1995;12:334-347.

    Google Scholar 

  66. Good CG, McDermont L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. 1995;274:538.

    Google Scholar 

  67. Polonia J, Boaventura I, Gama G, et al. Influence of nonsteroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. J Hypertens 13:925-931, 1995.

    Google Scholar 

  68. Johnson AG, Simons LA, Simons A, Friedlander Y, McCallum J. Non-steroidal anti-inflammatory drugs and hypertension in the elderly: A community-based cross-sectional study. Br J Clin Pharmacol 1993;35:455-459.

    Google Scholar 

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  1. Clinical Safety and Epidemiology, Novartis Pharma A.G., Basel, Switzerland

    Walter H. Aellig

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Aellig, W.H. Adverse Reactions to Antihypertensive Therapy. Cardiovasc Drugs Ther 12, 189–196 (1998). https://doi.org/10.1023/A:1007735311894

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