Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521.

Millar, J. A.; Derkx, F. H. M.; McLean, Kathleen; Reid, JL

doi:10.1111/j.1365-2125.1982.tb01990.x

Cited by 121 publications

(62 citation statements)

References 29 publications

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“…The early blood pressure fall may be related to inhibition of plasma converting enzyme, while the later maximum fall was associated with additional tissue ACE inhibition. The fall in blood pressure in both groups on both treatments was not associated with impaired orthostatic tolerance or significant increases in heart rate, consistent with our previous experience (Millar et al, 1982;Ajayi et al, 1985a).…”

Section: Discussionsupporting

confidence: 91%

Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Aa¹,

Hockings²,

Reid³

1986

Brit J Clinical Pharma

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The effect of age on the pharmacodynamic responses to converting enzyme inhibitors, enalapril and enalaprilat was investigated in nine young (22‐30 years) and nine sex‐matched elderly (65‐73 years), healthy volunteers. The groups differed in baseline blood pressure, young 121/64 mmHg, elderly 142/75 mmHg (P less than 0.01), but not in sodium intake or body weight. Both enalapril and enalprilat produced significant falls in blood pressure in both groups but no increase in heart rate in the supine or erect posture. The blood pressure fall was significantly greater in the elderly on both treatments and in both erect and supine posture. The greater fall in blood pressure in the elderly was associated with a more prolonged inhibition of plasma angiotensin converting enzyme activity. The apparent age‐related difference in response appears to be due to the difference in baseline blood pressures between the groups. Further study of the usefulness of chronic dosing with angiotensin converting enzyme inhibitors in hypertension in the elderly is indicated.

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Section: Discussionsupporting

confidence: 91%

Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Aa¹,

Hockings²,

Reid³

1986

Brit J Clinical Pharma

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“…Previous studies in subjects on free dietary intake Millar et al, 1982b) have suggested a natriuresis following a single dose of both MK421 and MK521. The present study, in which the sodium intake was fixed, confirms a significant natriuresis.…”

Section: Side Effectsmentioning

confidence: 94%

Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin‐angiotensin system and sodium excretion in normal man.

Hodsman¹,

Zabludowski²,

Zoccali³

et al. 1984

Brit J Clinical Pharma

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The immediate and long‐term effects of enalapril (MK421) and its lysine analogue (MK521) in once‐daily dosage, were compared in a study of 12 normal subjects. Both compounds lowered blood pressure equally throughout 24 h without causing tachycardia. The biochemical changes with MK521 were more sustained than with MK421, but this did not affect the magnitude of blood pressure reduction. Twenty‐four hours after the previous dose, with both active drugs, plasma renin concentration was significantly higher on day 8 than on day 1, though angiotensin I did not increase in proportion; this probably reflects a fall in renin‐ substrate with prolonged converting enzyme inhibition. There was an early natriuresis with each compound but this effect was no longer apparent after 8 days of continuous therapy. Both MK421 and MK521 were well tolerated with no serious side effects.

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“…We would like to report on an extension to the analysis of similar data which have been previously described (Millar et al, 1982 The Hill function probably represents a more physiological relationship between plasma drug concentration and plasma converting enzyme inhibition than the log concentration relationship, and also models the fact that there is an upper limit to the pharmacological effect. It would be interesting to analyse the more extensive data for each subject in the study of Biollaz et al (1982) as outlined above.…”

Section: Concentration Effect Modelling With Converting Enzyme Inhibimentioning

confidence: 99%

Concentration effect modelling with converting enzyme inhibitors in man [letter]

Kelman¹,

Reid²,

Millar³

1983

Brit J Clinical Pharma

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Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521.

Cited by 121 publications

References 29 publications

Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Enalapril (MK421) and its lysine analogue (MK521): a comparison of acute and chronic effects on blood pressure, renin‐angiotensin system and sodium excretion in normal man.

Concentration effect modelling with converting enzyme inhibitors in man [letter]

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