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Biomedical subjects

G Leonetti

Publications and source records attributed to G Leonetti.

At least 199 records · Page 11Linked to original sources
PubMed1976

Control of renin release: a review of experimental evidence and clinical implications.

Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment.

Adrenergic beta-Antagonists↗
PubMed1976

Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment.

Propranolol blood and plasma levels were measured after a single oral dose of 40 mg in patients with chronic renal failure, in patients undergoing regular dialysis treatment, and in healthy volunteers. Peak levels were observed in all cases within 1.5 to 3 hours. However, peak blood and plasma concentrations of propranolol in the chronic renal failure group were 2- to 3-fold higher (161 +/- 41 ng/ml) than those observed in the dialysis patients (47 +/- 9 ng/ml) and in the healthy volunteers (26 +/- 1 ng/ml). The apparent plasma clearance was also significantly reduced in the patients with chronic renal failure. The data suggest a reduced hepatic extraction in chronic renal failure patients. A significant increase in the fraction of the dose available to the systemic circulation was also found, together with a modification of apparent plasma half-life and volume of distribution in regular dialysis patients during the dialysis day as compared with the after-dialysis day. No extraction of propranolol by the dialyzer was noticed. Marked fluctuations in propranolol blood concentrations were also observed in patients on regular dialysis following continuous propranolol treatment. The suppressive effect of propranolol on plasma renin activity did not fully correlate with the hypotensive effect of the drug. On the basis of the reported data, propranolol should be used with great caution and at low doses in chronic renal failure.

Adult↗
PubMed1976

The use of drug concentration measurements in studies of the therapeutic response to propranolol.

The dose of propranolol which produces the optimal therapeutic effect in patients with angina pectoris has been found to vary widely among patients. Because the plasma concentration of propranolol also differs markedly due to interpatient variability in absorption it seemed possible that this might be the reason for the wide range of effective doses in angina and that plasma propranolol might provide a useful guide to therapeutic response. To examine this possibility we selected ten patients with coronary artery disease complicated by angina and studied them at varying propranolol doses to a maximum of 320 mg/day. Exercise capacity was tested on a treadmill and plasma propranolol concentration was measured by gas liquid chromatography. In seven normal subjects beta-blockade was quantified precisely as inhibition of exercise tachycardia and was related to plasma propranolol levels at various doses. Maximal beta-blockade occurred at 100 ng/ml of plasma propranolol, but the dose response curve of blockade was relatively flat and the ED50 of plasma propranolol was 8+/-1 ng/ml. In the patients maximal therapeutic benefit from propranolol occurred at 30+/-7 ng/ml and at a dose of 144 mg/day. This resulted in an increase in exercise capacity from an estimated 12-7+/-0-8 ml/kg/min of oxygen consumption during control to 17-2+/-1-1 ml/kg/min on the drug. Thus, there was a wide variation of both dose and concentration among these patients at the maximum therapeutic response. However, when plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 and 98% of total blockade. These studies indicated the extent of beta-blockade necessary to produce an effective therapeutic response in angina, but demonstrate that plasma drug levels provide no practical guide to therapy in patients with angina pectoris. A further study was conducted measuring plasma propranolol in twenty hypertensive patients to investigate the fall in blood pressure in relations to the change in plasma renin activity and the inhibition of cardiac adrenergic receptors. The inhibition of plasma renin closely resemble the response seen in heart rate inhibition in that the maximum response is seen at 100 ng/ml and the ED50 was 11 ng/ml. In contrast propranolol is shown only to begin to have a significant effect on blood pressure at a plasma level of 30 ng/ml and the effect becomes progressively greater as the plasma level increases. This suggests that the hypotensive effect of propranolol may be dissociated from the beta-blocking effects of cardiac and renin releasing receptors.

Angina Pectoris↗
PubMed1975

Hypotensive and renin-suppressing activities of propranolol in hypertensive patients.

1. In patients with mild or moderate essential hypertension, oral propranolol, given in incremental doses, produced a moderate but significant lowering of blood pressure which was correlated with the concentration of propranolol in plasma. 2. Propranolol also reduced plasma renin activity (PRA) in the supine posture, on standing and after intravenous frusemide. However, 'supine' and 'frusemide' PRA values were markedly reduced at a plasma concentration of propranolol that had little effect on blood pressure. 3. On administration of propranolol there was little correlation between blood pressure decrease and PRA suppression, and even less between pretreatment PRA values and hypotensive response. 4. It is concluded that in patients with mild and moderate hypertension and low or normal plasma renin activity, suppression of PRA is not an important determinant of the hypotensive response to propranolol.

Administration, Oral↗
PubMed1975

Studies of the absorption and removal of propranolol in hypertensive patients during therapy.

The variability of plasma propranolol concentrations has been determined in a large group of patients being treated with the drug. Although the average patient achieved a therapeutic plasma level with 160 mg/day, there was marked interpatient variation. This was found to be primarily the result of differences in effective absorption of the drug, which averaged 46% of the oral dose but ranged from 20 to 80%. Propranolol disappeared from plasma with a half-life of 4.7 hours and its removal appeared to follow dose independent kinetics with no evidence of saturation of hepatic metabolism. The derived pharmacokinetic values of volume of distribution and clearance rate have been used to provide guidelines for initiating propranolol therapy intravenously, and the schedule of 8 mg as a loading dose and 0.02 mg/min as a sustaining dose has been suggested.

Administration, Oral↗