Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Factors influencing the choice of antihypertensive agents Andrew J. Zweifler & Murray D. Esler To cite this article: Andrew J. Zweifler & Murray D. Esler (1976) Factors influencing the choice of antihypertensive agents, Postgraduate Medicine, 60:1, 81-85, DOI: 10.1080/00325481.1976.11714415 To link to this article: http://dx.doi.org/10.1080/00325481.1976.11714415
Published online: 07 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Calgary]
Date: 05 August 2017, At: 11:50
Downloaded by [University of Calgary] at 11:50 05 August 2017
• Many drugs are available for the treatment of hypertension, and new antihypertensive agents certainly will continue to be marketed. How should physicians choose among these? First, physicians should be aware that ali antihypertensive drugs can be categorized in a few groups according to major mechanisms of action 1 (eg, selective reduction of cardiac output, peripheral vascular resistance, or extracellular fluid volume) and that in general there is no reason to pre scribe more than one agent from any group at one time. Second, physicians should be knowledgeable about the side effects common to drugs in each major category and to widely used individual agents. Third, they should appreciate the persona!, social, and medical factors that are unique to individual patients and may complicate the use of certain antihypertensive drugs. These factors relate to age, sex, occupation, potential for adherence to a program of therapy, and associated health problems (table). Age, Sex, Occupation
In older patients with hypertension, orthostatic hypotension tends to develop quite readily during therapy with antihypertensive drugs. This tendency is probably related to blunting of baroreflex activity, 2 and it may be a serious problem with agents for which a marked orthostatic hypotensive effect is predictable owing to the mechanisms of drug action. It is therefore wise to avoid the use of guanethidine in treating elderly hypertensive patients and to caution ali older patients receiving any of the antihypertensive agents about the possibility of orthostatic hypotension. Problems with sexual function are common in men treated with antihypertensive agents. Guanethidine inhibits ejaculation in almost ali men treated with it and may secondarily produce impotence. We3 have also observed, as have others, 4 that Joss of potency in sexually active men treated with diuretics alone is not uncommon. Occasionally, the same problem arises during therapy with methyldopa. Men treated with the aldosterone antagonist spironolactone in small doses may have nipple tenderness or, not infrequently, gynecomastia as a side effect. This agent in large doses also may be troublesome to women, producing abnormal uterine bleeding.5 An association between reserpine use and breast cancer bas
Vol. 60 • No. 1 • July 1976 • POSTGRADUATE MEDICINE
factors influencing the choice of antihypertensive agents Andrew J. Zweifler, MD Murray D. Esler, MBBS, PhD
University of Michigan Medical Center Ann Arbor
Persona!, social, and medical factors unique to individuel patients have a bearing on the efficacy of specifie antihypertensive agents and on the frequency and severity of side effects. The factors relate to age, sex, occupation, potential for adherence to a prescribed program of therapy, and associated health problems. The importance of a simple, inexpensive program is emphasized.
81
Downloaded by [University of Calgary] at 11:50 05 August 2017
The cost of the drugs prescribed and the complexity of the regimen are very important aspects of antihypertensive therapy.
been noted, 6 although this has not been confirmed in recent studies. 7 Reserpine probably should not be prescribed for women if a suitable alternative drug is available. Reserpine also may interfere with mentation, so its use should be avoided if a patient's occupation requires alertness or a high leve! of intellectual ac ti vit y. Clonidine has a transient sedative effect which may be troublesome, eg, to a patient who drives a motor vehicle for a living. Guanethidine tends to produce hypotension not only when a subject is standing but also during physical exercise. For this reason, use of guanethidine should be avoided if a patient's occupation requires climbing, running, or sustained physical exertion. Potential for Adherence to Program of Therapy
Hypertensive patients tend to drop out of therapy, and many of those who continue to see their physicians as scheduled do not have well-controlled blood pressure. 8 Of the many factors contributing to this problem, sorne are in the province of the physician and the health care system. Other factors are unique to the patients. The cost of the drugs prescribed and the complexity of the regimen are very important aspects of antihypertensive therapy. If patients are to be expected to take the medications as long as they live, physicians should take into account the cost of the drugs when prescribing them. Cost is one reason for keeping therapy as simple as possible; in general, the fewer pills taken per day, the less is the cost. At the University of Michigan Hospital, a priee list of commonly prescribed antihypertensive agents is permanently posted in the hypertension clinic to remind the professional staff of this cost factor. The list is referred to regularly when therapeutic decisions are made.
82
Physicians should also make an effort to prescribe antihypertensive medication that does not have to be taken at frequent intervals, ie, many times a day, and should recommend schedules of administration that are convenient for the patients. The simpler the program of therapy, the greater is the likelihood that the patient will follow it. If a patient's blood pressure can be controlled with one pill each day, taken at breakfast or on retiring, that patient is much more likely to comply with the program of treatment than is a patient who must take multiple daily doses of different agents. For this reason, we have favored agents with a longer duration of action: diuretics such as chlorthalidone and polythiazide, and the longer-acting antiadrenergic drugs such as reserpine and guanethidine. We have also come to recognize that preparations combining two antihypertensive agents may be of value in simplifying programs for selected patients. We have recently tended to prescribe tablets which combine potassium-sparing and sulfonamidederivative diuretics for the control of diuretic-induced hypokalemia instead of troubling the patient with another prescription, for supplemental potassium. However, the risk of serious hyperkalemia associated with the use of potassium-sparing diuretics, eg, triamterene and spironolactone, in the presence of renal or hepatic insufficiency should be remembered. Associated Health Problems
Cerebrovascular disease-Although one of the major benefits of effective treatment of hypertension is a decrease in the incidence of stroke, clinical manifestations of cerebrovascular disease are still quite common in hypertensive subjects, particularly those in the older age group. After acute brain injury, blood pressure typically rises. Levels may
POSTGAADUATE MEDICINE • July 1976 • Vol. 60 • No. 1
relative seriousness of factors influencing choice of antlhypertenslve agents*
Downloaded by [University of Calgary] at 11:50 05 August 2017
ASSQCiated health problem or other factor lnfluenclng cholce of drug
Drug Thiazide diuretic
Advanced age
Methyldopa
Reserpine
+
+
Propranolol
Guanethidine
Hydralazine
++
Angina pectoris
++t
Branchial asthma
+++
Cardiac failure
+
Depressive illness
++
+++
Diabetes, insulin-dependent
++ +++:j:
+++ +++
Diabetes, maturity-onset
+
Hyperuricemia and gout
+++
Renal insufficiency
++§
+
*Graded + (minor consideration), + + (moderate consideration), and + + + (major consideration). tuse is permissible if propranolol is given concurrently. :I:Tricyclic antidepressant given concurrently will interfere with guanethidine's antihypertensive action. §If serum creatinine value exceeds 2.5 mg/1 00 ml, thiazides will be relatively ineffective; a "loop" diuretic such as furosemide should be used.
become alarmingly high in hypertensive patients following cerebral infarction. ln attempts to control blood pressure in patients with acute brain injury, avoidance of agents that tend to cause mental confusion is advisable, lest this effect be magnified. Reserpine given intramuscularly can be particularly troublesome in this regard. The same problem sometimes arises during treatment with methyldopa. Excessive. reduction of blood pressure also should be avoided, so collateral blood flow to ischemie brain tissue will not be reduced. If the use of antihypertensive agents is felt to be indieated in cases of fresh cerebral infarction, the preferred drugs are those with a fairly rapid onset of action and little tendency to cause profound hypotension~ eg, sodium nitroprusside given intravenously. Careful
Vol. 60 • No. 1 • July 1976 • POSTORADUATE MEDICINE
monitoring of blood pressure is necessary. Antihypertensive therapy is not contraindiçated in the presence of chronic cerebrovascular insufficiency. The elevated blood pressure should be reduced in hypertensive patients who have transient ischemie attacks. Even if hypotension should occur, an associated increase in frequency of· ischemie episodes would be unusual. 9 Of course, use of those antihypertensive agents that may produce severe orthostatic hypotension, such as guanethidine, should be avoided in these circumstances. Ischemie heart disease-Vasodilating antihypertensive agents, such as hydralazine, may induce or aggravate angina pectoris in patients with coronary artery disease. Fortunately, concomitant administration of the beta-adrenergie receptor blocker-pro-
83
Downloaded by [University of Calgary] at 11:50 05 August 2017
Andrew J. Zwelfler
Murray D. Esler
Or. Zweifler and Dr. Esler are in the hypertension division, department of internai medicine, University of Michigan Medical Center, Ann Arbor. Dr. Zweifler is professer of internai medicine and Dr. Esler is assistant professer of internai medicine, University of Michigan Medical School.
pranolol-eliminates this problem. A more rational approach to blood pressure control in the hypertensive patient with angina is the use of propranolol, with or without a diuretic, as the primary antihypertensive agent.* This may prove to control both problems.
Cardiac decompensation-Hypertensive patients who have a history of congestive heart failure or whose cardiac reserve is marginal should not be treated with propranolol. Cardiac function in such patients is heavily dependent on sympathetic "drive," and beta-adrenergic receptor blockade may cause cardiac decompensation. 10 Hypertensive patients with impaired cardiac function commonly are treated with digitalis preparations. lt is important to recognize that hypokalemia increases the sensitivity of the cardiac muscle to digitalis effects, predisposing the patients to digitalis toxicity. If diuretic agents are used to control blood pressure in patients taking digitalis, adequate potassium supplementation must be assured or diuretic combinations that do not produce hypokalemia should be used. Diabetes mellitus- The hypertensive *Not yet approved for this use by the FDA.
84
diabetic represents a special problem. Thiazide diuretics may accentuate the disturbance in carbohydrate metabolism in patients with latent or overt diabetes. In our experience, clinically apparent aggravation of diabetes by these agents is unusual, so we feel that diuretic therapy is not contraindicated in the presence of diaPetes. Nevertheless, a watchful eye should be kept on diabetics with maturity-onset disease who are so treated. Urine should be checked regularly at home, and blood glucose concentration should be measured periodically. Hyperglycemia, occasionally severe and sometimes associated with ketosis, could develop. A diabetic with insulin-dependent disease, particularly if it is "brittle," should not be treated with propranolol if sorne other approach to control of blood pressure is possible. Beta-adrenergic receptor blockade may contribute to the development of hypoglycemia11 and may mask its clinical manifestations. In sorne cases,l2 marked elevation of blood pressure in reaction to hypoglycemia has been observed; presumably this is secondary to unopposed alpha-adrenergic stimulation following hypoglycemia-induced release of catecholamines. Gout-Acute gouty arthritis may develop in hypertensive patients treated with thiazide diuretics. This problem is linked to the hyperuricemia which these drugs produce through their action on the kidneys. Patients with preexisting gout are particularly likely to get into difficulty if treated with thiazide diuretics. Every effort should be made to control blood pressure in gouty patients without using thiazides or chlorthalidone. lt should be recognized that both direct-acting vasodilators and adrenergic blocking drugs, with the exception of propranolol, cao promote fluid retention and are th us of limited value in sorne patients when used alone, without a diuretic. 13 • 14 If diuretics must be used, small doses of thiazide in combination with
POSTGAADUATE MEDICINE • July 1978 • Vol. 80 • No. 1
Downloaded by [University of Calgary] at 11:50 05 August 2017
potassium-sparing di ure tic, such as spironolactone or triamterene (which does not raise serum urie acid concentration), should be tried, or the use of thiazides and probenecid or allopurinol may be necessary. Renal insufficiency-Hypertensive patients with azotemia also present special problems. Drugs that tend to decrease renal blood flow should be avoided in the se cases. Guanethidine has been implicated in this regard. Hydralazine and methyldopa are less likely to cause difficulty of this sort. We· do not hesitate to prescribe diuretics for such patients, however, because blood pressure in most hypertensive patients with renal failure is difficult to control without salt and water depletion. In sorne patients, because of renal damage, conventional diuretics are ineffective, and more potent agents, such as furosemide, are necessary to obtain natriuresis. Great care should be taken in the use of spironolactone or triamterene because of the possibility of induction of serious hyperkalemia. Depressive il/ness-Antihypertensive therapy should be particularly careful in the presence of depressive illness. That certain
antiadrenergic drugs may aggravate depression must be recognized. The most notorious of these is reserpine, which not infrequently initiales profound depression. However, methyldopa may cause si mil ar difficulty, and it is likely that propranolol occasionally causes minor trouble of this sort. 15 Certain drugs that are used to treat depression may interact unfavorably with agents prescribed for the control of hypertension. The major offenders are the tricyclic antidepressants, such as imipramine, which impair the antihypertensive action of guanethidine or clonidine by interfering with entry of the drug into adrenergic neurons. Also, there is reason to believe that patients receiving methyldopa should not be treated with amphetamines. Conclusion
A number of factors unique to individual patients must be considered in developing programs of therapy for hypertension, and each therapeutic program modified accordingly. We hope to have provided sorne useful guidelines in this regard. • Address reprint requests to Andrew J. Zweifler, MD, University Hospital, Ann Arbor, Ml 48104.
References 1. Gifford RW Jr: Hypertension therapy 1974: A standard approach to therapy. Postgrad Med 56(5):20, Oct 1974 2. Johnson RH, Smith AC, Spalding JM, et al: Effect of posture on blood pressure in elderly patients. Lancet 1:731, 1965 3. Zweifler AJ, Esler MD, Randall OS: Diuretic-induced impotence in hypertensive patients. (To be published) 4. Mi ali WE: Report on the British MRC. Trial on the effects of treatment in mild established essential hypertension. Presented at Symposium on Nature and Prevention of Hypertensive Vascular Disease, Liège, Belgium, May 1975 5. Levitt JI: Spironolactone therapy and amenorrhea. JAMA 211:2014, 1970 6. Boston Collaborative Drug Surveillance Program: Reserpine and breast cancer. Lancet 2:669, 1974 7. O'Fallon WM, Labarthe DR. Kurland LT: Rauwolfia derivatives and breast cancer. Lancet 2:291, 1975 8. Schoenberger JA, Stamler J, Shekelle RB, et al: Current
Vol. 60 • No. 1 • July 1976 • POSTGRADUATE MEDICINE
9.
10. Il. 12. 13. 14.
15.
status of hypertension control in an industrial population. JAMA 222:559, 1972 Hypertension-Stroke Cooperative Study Group: Effect of antihypertensive treatment on stroke recurrence. JAMA 229:409, 1974 Prichard BN, Gillam PM: Use of propranolol (lnderal) in treatment of hypertension. Br Med J 2:725, 1964 Kotler MN. Berrnan L. Rubenstein AH: Hypoglycaemia precipitated by propranolol. Lancet 2:1389, 1966 McMurtry RJ: Propranolol, hypoglycemia and hypertensive crisis. (Letter) Ann Intem Med 80:669, 1974 Hamilton M. Kopelman H: Treatment of severe hypertension with methyldopa. Br Med J 1:151, 1963 Tarazi RC. Frohlich ED, Dustan HP: Plasma volume changes with long-term beta-adrenergic blockade. Am Heart J 82:770, 1971 Zacharias FJ. Cowen KJ, Presti J, et al: Propranolol in hypertension: A study of Iong-term therapy. 1964-1970. Am Heart J 83:755, 1972
85
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Factors influencing the choice of antihypertensive agents Andrew J. Zweifler & Murray D. Esler To cite this article: Andrew J. Zweifler & Murray D. Esler (1976) Factors influencing the choice of antihypertensive agents, Postgraduate Medicine, 60:1, 81-85, DOI: 10.1080/00325481.1976.11714415 To link to this article: http://dx.doi.org/10.1080/00325481.1976.11714415
Published online: 07 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Calgary]
Date: 05 August 2017, At: 11:50
Downloaded by [University of Calgary] at 11:50 05 August 2017
• Many drugs are available for the treatment of hypertension, and new antihypertensive agents certainly will continue to be marketed. How should physicians choose among these? First, physicians should be aware that ali antihypertensive drugs can be categorized in a few groups according to major mechanisms of action 1 (eg, selective reduction of cardiac output, peripheral vascular resistance, or extracellular fluid volume) and that in general there is no reason to pre scribe more than one agent from any group at one time. Second, physicians should be knowledgeable about the side effects common to drugs in each major category and to widely used individual agents. Third, they should appreciate the persona!, social, and medical factors that are unique to individual patients and may complicate the use of certain antihypertensive drugs. These factors relate to age, sex, occupation, potential for adherence to a program of therapy, and associated health problems (table). Age, Sex, Occupation
In older patients with hypertension, orthostatic hypotension tends to develop quite readily during therapy with antihypertensive drugs. This tendency is probably related to blunting of baroreflex activity, 2 and it may be a serious problem with agents for which a marked orthostatic hypotensive effect is predictable owing to the mechanisms of drug action. It is therefore wise to avoid the use of guanethidine in treating elderly hypertensive patients and to caution ali older patients receiving any of the antihypertensive agents about the possibility of orthostatic hypotension. Problems with sexual function are common in men treated with antihypertensive agents. Guanethidine inhibits ejaculation in almost ali men treated with it and may secondarily produce impotence. We3 have also observed, as have others, 4 that Joss of potency in sexually active men treated with diuretics alone is not uncommon. Occasionally, the same problem arises during therapy with methyldopa. Men treated with the aldosterone antagonist spironolactone in small doses may have nipple tenderness or, not infrequently, gynecomastia as a side effect. This agent in large doses also may be troublesome to women, producing abnormal uterine bleeding.5 An association between reserpine use and breast cancer bas
Vol. 60 • No. 1 • July 1976 • POSTGRADUATE MEDICINE
factors influencing the choice of antihypertensive agents Andrew J. Zweifler, MD Murray D. Esler, MBBS, PhD
University of Michigan Medical Center Ann Arbor
Persona!, social, and medical factors unique to individuel patients have a bearing on the efficacy of specifie antihypertensive agents and on the frequency and severity of side effects. The factors relate to age, sex, occupation, potential for adherence to a prescribed program of therapy, and associated health problems. The importance of a simple, inexpensive program is emphasized.
81
Downloaded by [University of Calgary] at 11:50 05 August 2017
The cost of the drugs prescribed and the complexity of the regimen are very important aspects of antihypertensive therapy.
been noted, 6 although this has not been confirmed in recent studies. 7 Reserpine probably should not be prescribed for women if a suitable alternative drug is available. Reserpine also may interfere with mentation, so its use should be avoided if a patient's occupation requires alertness or a high leve! of intellectual ac ti vit y. Clonidine has a transient sedative effect which may be troublesome, eg, to a patient who drives a motor vehicle for a living. Guanethidine tends to produce hypotension not only when a subject is standing but also during physical exercise. For this reason, use of guanethidine should be avoided if a patient's occupation requires climbing, running, or sustained physical exertion. Potential for Adherence to Program of Therapy
Hypertensive patients tend to drop out of therapy, and many of those who continue to see their physicians as scheduled do not have well-controlled blood pressure. 8 Of the many factors contributing to this problem, sorne are in the province of the physician and the health care system. Other factors are unique to the patients. The cost of the drugs prescribed and the complexity of the regimen are very important aspects of antihypertensive therapy. If patients are to be expected to take the medications as long as they live, physicians should take into account the cost of the drugs when prescribing them. Cost is one reason for keeping therapy as simple as possible; in general, the fewer pills taken per day, the less is the cost. At the University of Michigan Hospital, a priee list of commonly prescribed antihypertensive agents is permanently posted in the hypertension clinic to remind the professional staff of this cost factor. The list is referred to regularly when therapeutic decisions are made.
82
Physicians should also make an effort to prescribe antihypertensive medication that does not have to be taken at frequent intervals, ie, many times a day, and should recommend schedules of administration that are convenient for the patients. The simpler the program of therapy, the greater is the likelihood that the patient will follow it. If a patient's blood pressure can be controlled with one pill each day, taken at breakfast or on retiring, that patient is much more likely to comply with the program of treatment than is a patient who must take multiple daily doses of different agents. For this reason, we have favored agents with a longer duration of action: diuretics such as chlorthalidone and polythiazide, and the longer-acting antiadrenergic drugs such as reserpine and guanethidine. We have also come to recognize that preparations combining two antihypertensive agents may be of value in simplifying programs for selected patients. We have recently tended to prescribe tablets which combine potassium-sparing and sulfonamidederivative diuretics for the control of diuretic-induced hypokalemia instead of troubling the patient with another prescription, for supplemental potassium. However, the risk of serious hyperkalemia associated with the use of potassium-sparing diuretics, eg, triamterene and spironolactone, in the presence of renal or hepatic insufficiency should be remembered. Associated Health Problems
Cerebrovascular disease-Although one of the major benefits of effective treatment of hypertension is a decrease in the incidence of stroke, clinical manifestations of cerebrovascular disease are still quite common in hypertensive subjects, particularly those in the older age group. After acute brain injury, blood pressure typically rises. Levels may
POSTGAADUATE MEDICINE • July 1976 • Vol. 60 • No. 1
relative seriousness of factors influencing choice of antlhypertenslve agents*
Downloaded by [University of Calgary] at 11:50 05 August 2017
ASSQCiated health problem or other factor lnfluenclng cholce of drug
Drug Thiazide diuretic
Advanced age
Methyldopa
Reserpine
+
+
Propranolol
Guanethidine
Hydralazine
++
Angina pectoris
++t
Branchial asthma
+++
Cardiac failure
+
Depressive illness
++
+++
Diabetes, insulin-dependent
++ +++:j:
+++ +++
Diabetes, maturity-onset
+
Hyperuricemia and gout
+++
Renal insufficiency
++§
+
*Graded + (minor consideration), + + (moderate consideration), and + + + (major consideration). tuse is permissible if propranolol is given concurrently. :I:Tricyclic antidepressant given concurrently will interfere with guanethidine's antihypertensive action. §If serum creatinine value exceeds 2.5 mg/1 00 ml, thiazides will be relatively ineffective; a "loop" diuretic such as furosemide should be used.
become alarmingly high in hypertensive patients following cerebral infarction. ln attempts to control blood pressure in patients with acute brain injury, avoidance of agents that tend to cause mental confusion is advisable, lest this effect be magnified. Reserpine given intramuscularly can be particularly troublesome in this regard. The same problem sometimes arises during treatment with methyldopa. Excessive. reduction of blood pressure also should be avoided, so collateral blood flow to ischemie brain tissue will not be reduced. If the use of antihypertensive agents is felt to be indieated in cases of fresh cerebral infarction, the preferred drugs are those with a fairly rapid onset of action and little tendency to cause profound hypotension~ eg, sodium nitroprusside given intravenously. Careful
Vol. 60 • No. 1 • July 1976 • POSTORADUATE MEDICINE
monitoring of blood pressure is necessary. Antihypertensive therapy is not contraindiçated in the presence of chronic cerebrovascular insufficiency. The elevated blood pressure should be reduced in hypertensive patients who have transient ischemie attacks. Even if hypotension should occur, an associated increase in frequency of· ischemie episodes would be unusual. 9 Of course, use of those antihypertensive agents that may produce severe orthostatic hypotension, such as guanethidine, should be avoided in these circumstances. Ischemie heart disease-Vasodilating antihypertensive agents, such as hydralazine, may induce or aggravate angina pectoris in patients with coronary artery disease. Fortunately, concomitant administration of the beta-adrenergie receptor blocker-pro-
83
Downloaded by [University of Calgary] at 11:50 05 August 2017
Andrew J. Zwelfler
Murray D. Esler
Or. Zweifler and Dr. Esler are in the hypertension division, department of internai medicine, University of Michigan Medical Center, Ann Arbor. Dr. Zweifler is professer of internai medicine and Dr. Esler is assistant professer of internai medicine, University of Michigan Medical School.
pranolol-eliminates this problem. A more rational approach to blood pressure control in the hypertensive patient with angina is the use of propranolol, with or without a diuretic, as the primary antihypertensive agent.* This may prove to control both problems.
Cardiac decompensation-Hypertensive patients who have a history of congestive heart failure or whose cardiac reserve is marginal should not be treated with propranolol. Cardiac function in such patients is heavily dependent on sympathetic "drive," and beta-adrenergic receptor blockade may cause cardiac decompensation. 10 Hypertensive patients with impaired cardiac function commonly are treated with digitalis preparations. lt is important to recognize that hypokalemia increases the sensitivity of the cardiac muscle to digitalis effects, predisposing the patients to digitalis toxicity. If diuretic agents are used to control blood pressure in patients taking digitalis, adequate potassium supplementation must be assured or diuretic combinations that do not produce hypokalemia should be used. Diabetes mellitus- The hypertensive *Not yet approved for this use by the FDA.
84
diabetic represents a special problem. Thiazide diuretics may accentuate the disturbance in carbohydrate metabolism in patients with latent or overt diabetes. In our experience, clinically apparent aggravation of diabetes by these agents is unusual, so we feel that diuretic therapy is not contraindicated in the presence of diaPetes. Nevertheless, a watchful eye should be kept on diabetics with maturity-onset disease who are so treated. Urine should be checked regularly at home, and blood glucose concentration should be measured periodically. Hyperglycemia, occasionally severe and sometimes associated with ketosis, could develop. A diabetic with insulin-dependent disease, particularly if it is "brittle," should not be treated with propranolol if sorne other approach to control of blood pressure is possible. Beta-adrenergic receptor blockade may contribute to the development of hypoglycemia11 and may mask its clinical manifestations. In sorne cases,l2 marked elevation of blood pressure in reaction to hypoglycemia has been observed; presumably this is secondary to unopposed alpha-adrenergic stimulation following hypoglycemia-induced release of catecholamines. Gout-Acute gouty arthritis may develop in hypertensive patients treated with thiazide diuretics. This problem is linked to the hyperuricemia which these drugs produce through their action on the kidneys. Patients with preexisting gout are particularly likely to get into difficulty if treated with thiazide diuretics. Every effort should be made to control blood pressure in gouty patients without using thiazides or chlorthalidone. lt should be recognized that both direct-acting vasodilators and adrenergic blocking drugs, with the exception of propranolol, cao promote fluid retention and are th us of limited value in sorne patients when used alone, without a diuretic. 13 • 14 If diuretics must be used, small doses of thiazide in combination with
POSTGAADUATE MEDICINE • July 1978 • Vol. 80 • No. 1
Downloaded by [University of Calgary] at 11:50 05 August 2017
potassium-sparing di ure tic, such as spironolactone or triamterene (which does not raise serum urie acid concentration), should be tried, or the use of thiazides and probenecid or allopurinol may be necessary. Renal insufficiency-Hypertensive patients with azotemia also present special problems. Drugs that tend to decrease renal blood flow should be avoided in the se cases. Guanethidine has been implicated in this regard. Hydralazine and methyldopa are less likely to cause difficulty of this sort. We· do not hesitate to prescribe diuretics for such patients, however, because blood pressure in most hypertensive patients with renal failure is difficult to control without salt and water depletion. In sorne patients, because of renal damage, conventional diuretics are ineffective, and more potent agents, such as furosemide, are necessary to obtain natriuresis. Great care should be taken in the use of spironolactone or triamterene because of the possibility of induction of serious hyperkalemia. Depressive il/ness-Antihypertensive therapy should be particularly careful in the presence of depressive illness. That certain
antiadrenergic drugs may aggravate depression must be recognized. The most notorious of these is reserpine, which not infrequently initiales profound depression. However, methyldopa may cause si mil ar difficulty, and it is likely that propranolol occasionally causes minor trouble of this sort. 15 Certain drugs that are used to treat depression may interact unfavorably with agents prescribed for the control of hypertension. The major offenders are the tricyclic antidepressants, such as imipramine, which impair the antihypertensive action of guanethidine or clonidine by interfering with entry of the drug into adrenergic neurons. Also, there is reason to believe that patients receiving methyldopa should not be treated with amphetamines. Conclusion
A number of factors unique to individual patients must be considered in developing programs of therapy for hypertension, and each therapeutic program modified accordingly. We hope to have provided sorne useful guidelines in this regard. • Address reprint requests to Andrew J. Zweifler, MD, University Hospital, Ann Arbor, Ml 48104.
References 1. Gifford RW Jr: Hypertension therapy 1974: A standard approach to therapy. Postgrad Med 56(5):20, Oct 1974 2. Johnson RH, Smith AC, Spalding JM, et al: Effect of posture on blood pressure in elderly patients. Lancet 1:731, 1965 3. Zweifler AJ, Esler MD, Randall OS: Diuretic-induced impotence in hypertensive patients. (To be published) 4. Mi ali WE: Report on the British MRC. Trial on the effects of treatment in mild established essential hypertension. Presented at Symposium on Nature and Prevention of Hypertensive Vascular Disease, Liège, Belgium, May 1975 5. Levitt JI: Spironolactone therapy and amenorrhea. JAMA 211:2014, 1970 6. Boston Collaborative Drug Surveillance Program: Reserpine and breast cancer. Lancet 2:669, 1974 7. O'Fallon WM, Labarthe DR. Kurland LT: Rauwolfia derivatives and breast cancer. Lancet 2:291, 1975 8. Schoenberger JA, Stamler J, Shekelle RB, et al: Current
Vol. 60 • No. 1 • July 1976 • POSTGRADUATE MEDICINE
9.
10. Il. 12. 13. 14.
15.
status of hypertension control in an industrial population. JAMA 222:559, 1972 Hypertension-Stroke Cooperative Study Group: Effect of antihypertensive treatment on stroke recurrence. JAMA 229:409, 1974 Prichard BN, Gillam PM: Use of propranolol (lnderal) in treatment of hypertension. Br Med J 2:725, 1964 Kotler MN. Berrnan L. Rubenstein AH: Hypoglycaemia precipitated by propranolol. Lancet 2:1389, 1966 McMurtry RJ: Propranolol, hypoglycemia and hypertensive crisis. (Letter) Ann Intem Med 80:669, 1974 Hamilton M. Kopelman H: Treatment of severe hypertension with methyldopa. Br Med J 1:151, 1963 Tarazi RC. Frohlich ED, Dustan HP: Plasma volume changes with long-term beta-adrenergic blockade. Am Heart J 82:770, 1971 Zacharias FJ. Cowen KJ, Presti J, et al: Propranolol in hypertension: A study of Iong-term therapy. 1964-1970. Am Heart J 83:755, 1972
85
