Abstract
An often-stated comment from researchers in aging is that the consistent hallmark of increasing age is increasing variability for measured parameters within a population. The various components of cardiovascular function in the aging human generally fit this maxim. Here an attempt will be made to characterize aspects of pharmacodynamic variability in aging and explore some of the various components of physiological variability that contribute to measurable pharmacodynamic endpoints. The approach will stress that useful cardiovascular pharmacodynamic endpoints (e. g., blood pressure, heart rate, cardiac output, etc.) are complex parameters derived from interacting components. Blood pressure, for example, characterized in terms of hemodynamics is a function of cardiac output, vascular compliance, and vascular resistance. Cardiac output is comprised of heart rate and contractility, while contractility may be usefully separated into systolic and diastolic components.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
R. J. Rodeheffer, G. Gerstenblith, L. C. Becker, J. L. Fleg, M. L. Weisfeldt, and E. G. Lakatta. Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for diminished heart rate. Circulation 69:203–213 (1984).
R. O. Bonow, S. L. Bacharach, M. V. Green, K. M. Kent, D. R. Rosing, L. C. Lipson, M. B. Leon, and S. E. Epstein. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation 64:315–323 (1981).
R. O. Bonow, D. F. Vitale, S. L. Bacharach, B. J. Maron, and M. V. Green. Effects of aging on asynchronous left ventricular regional function and global ventricular filling in normal human subjects. J. Am. Coll. Cardiol. 11:50–58 (1988).
A. P. Avolio, S. G. Chen, R. P. Wang, et al. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 68:50–58 (1983).
F. H. Messerli, K. Sundgaard-Riise, H. O. Ventura, F. G. Dunn, L. B. Glade, and E. D. Frolich. Essential hypertension in the elderly: hemodynamics, intravascular volume, plasma renin activity, and circulating catecholamine levels. Lancet 2:983–986 (1983).
R. E. Vestal, A. J. J. Wood, and D. G. Shand. Reduced beta-adrenoceptor sensitivity in the elderly. Clin. Pharmacol. Ther. 26:181–186 (1979).
H. Y. Pan, B. B. Hoffman, R. A. Pershe, and T. F. Blaschke. Decline in beta-adrenergic receptor-mediated vascular relaxation with aging in man. J. Pharmacol. Exp. Ther. 239:802–807 (1986).
J. H. Chin and B. B. Hoffman. Age-related deficit in beta receptor stimulation of cAMP binding in blood vessels. Mech. Ageing Dev. 53:111–125 (1990).
C. Klein, J. G. Gerber, N. A. Payne, and A. S. Nies. The effect of age on the sensitivity of the α-1-adrenoceptor to phenylephrine and prazosin. Clin. Pharmacol. Ther. 47:535–539 (1990).
P. J. W. Scott and J. C. Reid. The effect of age on the responses of human isolated arteries to noradrenaline. Brit. J. Clin. Pharmaco. 13:237–239 (1982).
V. J. Dzau. Multiple pathways of angiotensin production in the blood vessel wall: evidence, possibilities, and hypotheses. J. Hypertens. 7:933–936 (1989).
G. H. Williams. Converting-enzyme inhibitors in the treatment of hypertension. N. Engl. J. Med. 319:1517–1525 (1988).
R. H. Noth, M. N. Lassman, and S. V. Tan. Age and the renin-aldosterone system. Arch. Intern. Med. 137:1414–1420 (1977).
D. J. Webb, N. Benjamin, M. J. Allen, J. Brown, M. O’Flynn, and J. R. Cockroft. Vascular responses to local atrial natriuretic peptide infusion in man. Brit. J. Clin. Pharmaco. 26:245–251 (1988).
P. Vallance, J. Collier, and S. Moncada. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 2:997–1000 (1989).
J. G. Clarke, N. Benjamin, S. W. Larkin, D. J. Webb, G. J. Davies, and A. Maseri. Endothelin is a potent long-lasting vasoconstrictor in men. Am. J. Physiol. 257:H2033–H2035 (1989).
C. Garland, E. Barrett-Connor, L. Suarez, and M. H. Criqui. Isolated systolic hypertension and mortality after age 60 years, A prospective population-based study. Am. J. Epidemiol. 118:365–376 (1983).
S. C. Montamat and D. R. Abernethy. Calcium antagonists in geriatric patients: Diltiazem in elderly hypertensives. Clin. Pharmacol. Ther. 45:682–691 (1989).
D. R. Abernethy, J. Gutkowska, and L. M. Winterbottom. Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: Pharmacodynamics in relation to disposition. Clin. Pharmacol. Ther. 48:76–86 (1990).
J. Fraser, J. Nadeau, D. Robertson, and A. J. J. Wood. Regulation of human leukocyte beta receptors by endogenous catecholamines: relationship of leukocyte beta receptor density to the cardiac sensitivity to isoproterenol. J. Clin. Invest. 67:1777–1784 (1981).
I. M. Ramzan and G. Levy. Kinetics of drug action in disease states. XV: Effect of pregnancy on the convulsive activity of pentylenetetrazol in rats. J. Pharm. Sci. 74:1233–1235 (1985).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Abernethy, D.R. (1991). Variability in Human Cardiovascular Pharmacodynamics. In: D’Argenio, D.Z. (eds) Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9021-4_7
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9021-4_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9023-8
Online ISBN: 978-1-4757-9021-4
eBook Packages: Springer Book Archive