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Hemodynamic and metabolic effects of intravenous clentiazem in hypertensive patients
E D Frohlich1, M McLoughlin, R Ketelhut
1Department of Internal Medicine, Ochsner Clinic, New Orleans, Louisiana.
Insights
Clentiazem, a calcium antagonist, lowered blood pressure by reducing peripheral resistance in hypertensive patients. It also altered hormone levels, including reduced aldosterone and increased epinephrine, highlighting the diverse effects of this drug class.
Area of Science:
- Cardiovascular Pharmacology
- Endocrinology
Background:
- Essential hypertension remains a significant global health concern.
- Calcium antagonists are a key therapeutic class for managing hypertension.
- Diltiazem congeners are explored for their unique pharmacological profiles.
Purpose of the Study:
- To investigate the hemodynamic and metabolic effects of clentiazem in patients with essential hypertension.
- To compare the effects of clentiazem with previously observed effects of diltiazem.
Main Methods:
- Intravenous administration of clentiazem to 10 untreated essential hypertensive patients in 3 successive doses (1.0 mg/kg total).
- Monitoring of hemodynamic parameters: mean arterial pressure, total peripheral resistance, heart rate, and cardiac output.
- Measurement of plasma and serum levels: aldosterone, potassium, calcium, norepinephrine, and epinephrine.
Main Results:
- Clentiazem significantly reduced mean arterial pressure and total peripheral resistance, while heart rate remained unchanged.
- Cardiac output increased due to augmented cardiopulmonary volume, linked to peripheral venoconstriction and norepinephrine release.
- Unexpectedly, clentiazem caused a reduction in plasma aldosterone, serum potassium, and serum calcium, alongside an increase in plasma epinephrine.
Conclusions:
- Clentiazem effectively lowers blood pressure by decreasing total peripheral resistance.
- The observed hormonal changes (epinephrine increase, aldosterone decrease) are distinct from those seen with diltiazem.
- These findings emphasize the heterogeneity among calcium channel blockers regarding their antihypertensive mechanisms and metabolic effects.
Abstract:
To determine the hemodynamic and certain metabolic effects of clentiazem, a diltiazem congener, 10 untreated essential hypertensive patients were given the calcium antagonist in 3 successive doses totaling 1.0 mg/kg intravenously. Mean arterial pressure and total peripheral resistance progressively declined from 121 +/- 3 mm Hg and 47 +/- 2 U (mean) to 110 +/- 3 mm Hg and 33 +/- 1 U, respectively (p less than 0.05); heart rate remained unchanged. Cardiac output increased as a result of augmented cardiopulmonary volume (p less than 0.05) produced by peripheral venoconstriction and norepinephrine release (from 258 +/- 41 to 319 +/- 42 pg/ml; p less than 0.01). Surprisingly, there was an immediate reduction in plasma aldosterone (10.4 +/- 1.2 to 6.5 +/- 1.0 ng/dl; p less than 0.01), serum potassium (4.3 +/- 0.1 to 3.6 +/- 0.1 mEq/dl; p less than 0.001) and calcium (9.5 +/- 0.1 to 8.8 +/- 0.1 mg/dl; p less than 0.001) concentrations, whereas epinephrine increased (21.2 +/- 3.3 to 45.8 +/- 5.9 pg/ml; p less than 0.002). Previous studies with diltiazem, conducted similarly, did not show these changes. Therefore, clentiazem reduced mean arterial pressure through a decrease in total peripheral resistance, and released epinephrine was associated with intracellular potassium influx (urinary potassium did not change). The inhibited aldosterone release was not compensated by altered renal blood flow, glomerular filtration or increased plasma renin activity. These findings underscore the concept that calcium antagonists are a remarkably heterogeneous antihypertensive group.