[Regression of hypertrophy of the left ventricle in patients with hypertension after 6-month treatment with Fludex]. / Regression der Hypertrophie des linken Ventrikels bei Patienten mit Hypertonie nach 6monatiger Behandlung mit Fludex.

Indapamide (Fludex) administered in daily doses of 2.5 mg resulted in optimal improvement of the blood pressure in patients with mild or moderate hypertension. During the period of 6 months treatment that was tolerated well by the patients, no influence of indapamide on the levels of glucose, cholesterol, triglycerides, and creatinine in blood was observed. A mild decrease of serum potassium in blood was clinically not relevant. Using echocardiography and electrocardiography a regression of the hypertrophy of the left ventricle of the heart was observed.

Beta blockers induce different intrarenal effects in humans: demonstration by selective infusion of tertatolol and propranolol.

The effects of tertatolol and propranolol on renal circulation were studied in patients with normal renal function to test the hypothesis that various beta blockers may have different vasomotor effects within the renal vascular bed. Left renal blood flow was measured by the continuous thermodilution method before (t0), and 5 (t1), 10 (t2), 20 (t3), and 30 (t4) minutes after a selective infusion of tertatolol (0.25 mg, N = 4) or propranolol (2.5 mg, N = 4) into the left renal artery. Heart rate, cardiac output, aortic and right atrial pressures, and systemic vascular resistances did not significantly vary after either drug throughout the study. Plasma renin activity and plasma aldosterone in arterial and renal venous blood started to decrease at t1 after each drug. After propranolol, renal blood flow, renal vascular resistance and the renal arteriovenous oxygen difference were unchanged. Conversely, after tertatolol at t3, renal blood flow was increased (from 426 +/- 18 mL/min/1.73 m2 to 509 +/- 56 mL/min/1.73 m2, P = .03), renal vascular resistance and renal arteriovenous oxygen difference were decreased (P less than .001), and the renal blood flow/cardiac output ratio was increased (P = .03). The filtration fraction did not vary after either drug, as attested by the unchanged polyfructosan extraction coefficient. This clinical study shows that selective infusion of a single low dose of tertatolol into the renal artery results in a delayed intrarenal vasodilator effect, while at the dose tested propranolol does not modify renal hemodynamics.

Structure-activity relationships as a response to the pharmacological differences in beta-receptor ligands.

With a few notable exceptions, beta-receptor ligands (agonists and antagonists) belong to the aryl- or heteroaryl-ethanolamine series and to the aryl- or heteroaryl-oxypropanolamine series. Structure-activity relationships for beta-adrenergic agonists show that a secondary amine in the phenylethanolamine side chain ending is essential for receptor stimulation. The 3,4-dihydroxyphenyl groups may be replaced by "phenol equivalents" (-CH2OH, -NHCONH2, -CHOH, -NHSO2CH3). In contrast, substitution at carbon alpha of the phenyl-ethanolamine side chain decreases or suppresses beta-adrenergic activity. The general requirements for beta-adrenergic blocking activity in the aryl- or heteroaryl-oxypropanolamine are as follows: (1) the potency of beta-blockade is conferred by a branched alkyl group (isopropyl or tert-butyl) grafted on the terminal amino N, and by the nature and position of a substituent on the aromatic ring: ortho-substituted compounds (especially when they have an hetero-atom in alpha) are the most potent ones. (2) The cardioselectivity is improved by the attachment of 3,4-dimethoxyphenylethyl,4-amide-substituted phenoxyethyl or acylamino-alkyl moieties to the terminal amino N of the side chain. Para substitution on the aromatic ring (particularly 4-acylamido substitution) has also yielded cardioselective drugs. Finally, the beta 1-selectivity is strongly and negatively correlated with lipophilicity. (3) Intrinsic sympathomimetic activity can be modulated by aromatic nucleus variations, particularly by hydroxyl-equivalents (electron withdrawing groups) on meta- and para-positions (3,4-substitutions).

Tertatolol in hypertension. Long-term therapy in 2,338 patients.

Tertatolol has been studied in 2,338 patients with mild to moderate hypertension over a one year period. Tertatolol (T) was initiated alone (5 mg once daily) and if satisfactory control of blood pressure (BP) (diastolic BP less than 95 mm Hg) was not achieved, treatment was adapted at the third or sixth month either by increasing the dosage (heart rate greater than 70 beats/min), or by adding a potassium-sparing diuretic (heart rate less than or equal to 70 beats/min). Blood pressure normalization was achieved in 88.8% of the study population: 66.1% on single and 22.7% on dual therapy. The decrease of diastolic BP was 18.4 mm Hg (from 102.8 +/- 0.2 to 84.4 +/- 0.2 mm Hg, P less than .001). Tertatolol alone or associated with diuretic (T + D) induced a significant and continuous decrease in supine systolic and diastolic BP. Overall side effects were rare, leading in only 6.5% of the cases to the discontinuation of the drug. Plasma creatinine significantly decreased in the single therapy group only (from 92.2 +/- 0.5 to 90.1 +/- 0.5 mumol/L, P less than .01). In patients with initial plasma creatinine greater than or equal to 100 mumol/L (n = 661), plasma creatinine markedly decreased (-10%, from 114.6 +/- 0.7 to 103.4 +/- 0.8 mumol/L, P less than .01), and to the same extent with T or T + D. Thus, this large-scale study confirms that tertatolol is an efficient and well-tolerated antihypertensive drug, which improves renal function, especially when initially reduced.

Prolonged beta blockade due to tertatolol: a comparative study with propranolol and atenolol.

Submaximal exercise heart rate was measured after oral administration of placebo, tertatolol 5 mg, propranolol 80 mg, and atenolol 100 mg to 12 subjects in a double-blind cross-over study. The peaks of beta-blocking activity, observed at 2 hr, were of similar extent for the 3 drugs. The duration of activity of tertatolol, a beta blocker with a short elimination half-life, extended up to 24 hr as did that of atenolol, but was longer than that of propranolol which reached only 18 hr. These results support once-daily administration of tertatolol in therapy.