Research Article| Volume 7, ISSUE 3, P607-623, September 1987

Download started.


The Antihypertensive Agents: Clinical Pharmacology and Therapeutic Monitoring

  • William B. White
    Corresponding author: University of Connecticut Health Center, Hypertension Unit (L-2071A), Farmington, CT 06032
    Associate Professor of Medicine, University of Connecticut School of Medicine, and Director, Hypertension Unit, John Dempsey Hospital of the University of Connecticut Health Center, Farmington, Connecticut
    Search for articles by this author
  • Rashmikant S. Pandit
    Instructor in Medicine, General Medicine and Hypertension Units, University of Connecticut School of Medicine, Farmington, Connecticut
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      There are currently six major classes of antihypertensive drugs. This article focuses on those agents developed and marketed since 1980, paying particular attention to the pharmacokinetics and pharmacodynamics of the various compounds.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Abrahms J.H.
        • Schulman P.
        • White W.B.
        Successful treatment of a monoamine oxidase inhibitor-tyramine hypertensive emergency with intravenous labetalol.
        N Engl J Med. 1985; 313: 52
        • Anavekar S.N.
        • Christophidis N.
        • Louis W.J.
        • Doyle A.E.
        Verapamil in the treatment of hypertension.
        J Cardiovasc Pharmacol. 1981; 3: 287-297
        • Au W.Y.M.
        • Dring L.G.
        • Grahame-Smith D.G.
        • et al.
        The metabolism of 14C-labeled alpha-methyldopa in normal and hypertensive human subjects.
        Biochem J. 1972; 129: 1-10
        • Beerman B.
        • Groschinsky-Grind M.
        Clinical pharmacokinetics of diuretics.
        Clin Pharmacokinet. 1980; 5: 227-245
        • Beyer K.H.
        • Baer J.E.
        Physiologic basis for the action of newer diuretic agents.
        Pharmacol Rev. 1961; 13: 517-562
        • Brater D.C.
        Pharmacodynamic considerations in the use of diuretics.
        Annu Rev Pharmacol Toxicol. 1983; 23: 45-62
        • Corvol P.
        • Claire M.
        • Oblin M.E.
        • et al.
        Mechanism of the antimineralocorticoid effects of spironolactone.
        Kidney Int. 1981; 20: 1-6
        • Cruickshank J.M.
        The clinical importance of cardioselectivity and lipophilicity in beta blockers.
        Am Heart J. 1980; 100: 160-166
        • Davies R.O.
        • Irvin J.D.
        • Kramsch D.K.
        • et al.
        Enalapril: Worldwide experience.
        Am J Med. 1984; 77: 23-35
        • Day M.O.
        • Rand M.L.
        Some observations on the pharmacology of alpha-methyldopa.
        Br J Pharmacol. 1964; 22: 72-86
        • Dustan H.P.
        Pathophysiology of hypertension.
        in: Hurst J.W. The Heart. Edition 5. McGraw-Hill, New York1982: 1171-1181
        • Eichelbaum M.
        Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response.
        Br J Clin Pharmacol. 1980; 10: 527-529
        • Fagard I.
        • Amery A.
        • Lijnen P.
        • Reybrouck T.
        Hemodynamic effects of captopril in hypertensive patients: Comparison with saralasin.
        Clin Sci. 1979; 57: 131-134
        • Fleckenstein A.
        Fundamentale Herz- und Gefasswirkungen Ca++-antagonischer Koronartherapeutika.
        Med Klin. 1975; 70: 1665-1674
        • Franciosa J.A.
        • Wilen M.M.
        • Jordan R.A.
        Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure.
        J Am Coll Cardiol. 1985; 5: 101-107
        • Frishman W.H.
        Calcium-channel blockers for hypertensive emergencies.
        J Clin Hypertension. 1986; 3: 553-613
        • Frishman W.H.
        • Charlap S.
        • Goldberger J.
        • et al.
        Comparison of diltiazem and nifedipine for both angina pectoris and systemic hypertension.
        Am J Cardiol. 1985; 56: 41-46
        • Frishman W.H.
        • Kostis J.
        The significance of intrinsic sympathomimetic activity in beta-adrenoreceptor blocking drugs.
        Cardiovasc Rev Rep. 1982; 3: 503-510
        • Frishman W.H.
        • Silverman R.
        Clinical pharmacology of the new beta-adrenergic blocking drugs. 2. Physiologic and metabolic effects.
        Am Heart J. 1979; 97: 797-807
        • Hansen K.B.
        • Bender A.D.
        Changes in serum potassium levels occurring in patients treated with triamterene and triamterene-hydrochlorothiazide combination.
        Clin Pharmacol Ther. 1967; 8: 392-399
        • Hermann P.
        • Rodger S.D.
        • Remones G.
        • et al.
        Pharmacokinetics of diltiazem after intravenous and oral administration.
        Eur J Clin Pharmacol. 1983; 24: 349-352
        • Hollander W.
        • Wilkins R.
        Chlorothiazide: A new type of drug for the treatment of arterial hypertension.
        Boston Med Q. 1957; 8: 69-73
        • Hypertension Detection and Follow-up Program Cooperative Group
        The effect of treatment on mortality in ‘mild’ hypertension.
        N Engl J Med. 1983; 307: 976-980
        • Imai M.
        Effect of bumetanide and furosemide on the thick ascending limbs of Henle’s loop of rabbits and rats performed in vitro.
        Eur J Pharmacol. 1977; 41: 409-416
        • Jarrott B.
        • Drummer O.
        • Hooper R.
        • et al.
        Pharmacokinetic properties of captopril after acute and chronic administration to hypertensive subjects.
        Am J Cardiol. 1982; 49: 1547-1549
        • Katz A.M.
        Pharmacology and mechanisms of action of calcium-channel blockers.
        J Clin Hypertension. 1986; 3: 28S-37S
        • Klein H.O.
        • Lang R.
        • Weiss E.
        • et al.
        The influence of verapamil on serum digoxin concentration.
        Circulation. 1982; 65: 998-1003
        • Klein W.
        • Brandt D.
        • Vrecko K.
        • Harriger M.
        Role of calcium antagonists in the treatment of essential hypertension.
        Circ Res. 1983; 52: 174-181
        • Kripalani K.J.
        • McKinstry D.N.
        • Singhvi S.M.
        • et al.
        Disposition of captopril in normal subjects.
        Clin Pharmacol Ther. 1980; 27: 636-641
        • Lasseter K.C.
        • Shambler E.D.
        • Murdoch A.A.
        • et al.
        Steady-state pharmacokinetics of nitrendipine in hepatic insufficiency.
        J Cardiovasc Pharmacol. 1984; 6: S977-S981
        • Lowenthal D.T.
        • Affrine M.B.
        Pharmacology and pharmacokinetics of minoxidil.
        J Cardiovasc Pharmacol. 1980; 2: S93-S106
        • MacClean A.J.
        • DuSovich P.
        • Barron K.W.
        Interaction of hydralazine with tension development and mechanism of calcium accumulation in K+ stimulated aortic strips.
        J Pharmacol Exp Ther. 1978; 207: 40-48
        • Muller F.B.
        • Bolli P.
        • Erne P.
        • et al.
        Antihypertensive therapy with long-acting calcium antagonist nitrendipine.
        J Cardiovasc Pharmacol. 1984; 6: S1073-S1076
        • Mylecharane E.J.
        • Raper C.
        Beta-receptor blocking and cardiodepressant actions of 2-nitrilophenoxypropanolamine.
        Eur J Pharmacol. 1971; 16: 14-20
        • McCallister R.G.
        • Kirston E.B.
        The pharmacology of verapamil. IV. Kinetic and dynamic effects after single intravenous and oral doses.
        Clin Pharmacol Ther. 1982; 31: 418-426
        • McMahon F.G.
        • Ryan J.R.
        • Jain A.K.
        • et al.
        Guanabenz in essential hypertension.
        Clin Pharmacol Ther. 1977; 21: 272-277
        • O’Conner P.T.
        Response of the renal kallikrein-kinin system, intravascular volume, and renal hemodynamics to sodium restriction and diuretic therapy in essential hypertension.
        Hypertension. 1981; 4: 72-78
        • O’Malley K.
        • Segal J.L.
        • Israili Z.H.
        • et al.
        Duration of hydralazine action in hypertension.
        Clin Pharmacol Ther. 1975; 18: 581-586
        • Packer M.
        • Lee W.H.
        • Yushak M.
        • Medina N.
        Comparison of captopril and enalapril in patients with severe chronic heart failure.
        N Engl J Med. 1986; 315: 847-853
        • Raemsch K.
        • Sommer J.
        Pharmacokinetics and metabolism of nitrendipine.
        in: Scriabine A. Vanov S. Deck K. Nitrendipine. Urban & Schwarzenberg, Baltimore1984: 409-421
        • Reece P.A.
        • Cozamanis I.
        • Zacest R.
        Kinetics of hydralazine and its main metabolites in slow and fast acetylators.
        Clin Pharmacol Ther. 1980; 28: 769-778
        • Salvetti A.
        • Pedrinelli R.
        • Magagna A.
        • et al.
        Influence of food on acute and chronic effects of captopril in essential hypertensive patients.
        J Cardiovasc Pharmacol. 1985; 7: S25-S29
        • Shaw J.E.
        Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route.
        Am Heart J. 1984; 108: 217S-223S
        • Stanaszek W.F.
        • Kellerman K.
        • Brogden R.N.
        • Romankiewicz J.A.
        Prazosin update: A review of its pharmacologic properties and therapeutic uses in hypertension.
        Drugs. 1983; 25: 339-384
        • Sweet C.S.
        Pharmacologic properties of the converting enzyme inhibitor, enalapril maleate (MK-421).
        Fed Proc. 1983; 42: 167-170
      1. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.
        Arch Int Med. 1984; 144: 1045-1057
        • Van Breeman C.
        • Hwang O.
        • Meisheri K.D.
        The mechanisms of inhibiting action of diltiazem on vascular smooth muscle contractility.
        J Pharmacol Exp Ther. 1981; 218: 459-464
        • Veterans Administration Cooperative Study Group on Antihypertensive Agents.
        Effects of treatment on morbidity in hypertension: I. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg.
        JAMA. 1967; 202: 1028-1034
        • Veterans Administration Cooperative Study Group on Antihypertensive Agents.
        Effects of treatment on morbidity in hypertension: II. Results in patients with diastolic blood pressures averaging 90 through 114 mm Hg.
        JAMA. 1970; 213: 1143-1152
      2. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Low-dose captopril for the treatment of mild to moderate hypertension.
        Arch Intern Med. 1984; 144: 1947-1953
        • Warltier D.C.
        • Lamping K.A.
        • Zyvoloski M.G.
        • et al.
        The slow-channel calcium blocking agent, nitrendipine, and coronary blood flow.
        J Cardiovasc Pharmacol. 1983; 5: 277-281
        • Wong S.H.
        • Marzouk N.
        • White W.B.
        Measurement of calcium-channel blockers by HPLC. Procedure Manual on the Laboratory Diagnosis of Cardiovascular Disorders. Institute for Clinical Science, Philadelphia1985: 155-160
        • White W.B.
        Beta blockers with intrinsic sympathomimetic activity.
        Am Fam Phys. 1985; 31: 115-118
        • White W.B.
        Clinical evaluation of the new antihypertensive agents.
        Therapeutic Drug Monitoring Program, American Association for Clinical Chemistry. 1986; 7: 1-7
        • White W.B.
        The management of hypertension during lactation.
        Hypertension. 1984; 6: 297-300
        • White W.B.
        • Smith V.E.
        • McCabe E.J.
        • Meeran M.K.
        Effects of chronic nitrendipine on casual (office) and ambulatory blood pressure.
        Clin Pharmacol Ther. 1985; 38: 60-64
        • White W.B.
        • Viadero J.J.
        • Lane T.J.
        • Podesla S.
        Effects of combination therapy with captopril and nifedipine in severe or resistant hypertension.
        Clin Pharmacol Ther. 1986; 39: 43-48
        • Zusman R.M.
        Regulation of prostaglandin biosynthesis in cultured renal medullary interstitial cells.
        in: Dunn M.J. Patrono C. Cinotti G.A. Prostaglandins and the Kidney. Plenum Press, New York1983: 17-25
        • Zusman R.M.
        Renin and non-renin-mediated antihypertensive actions of converting enzyme inhibitors.
        Kidney Int. 1984; 25: 969-983