Cristiano Barbieri

Metabolic effects of prazosin

The effects of oral administration of 2 mg prazosin on several metabolic and endocrine variables were evaluated in 12 patients with hypertension (6 with normal and 6 with abnormal glucose tolerance). Prazosin was followed by a rise in plasma glucose and serum free fatty acids (FFA) in both normal and diabetic subjects; there was a trend upward in serum insulin (IRI), but growth hormone (GH), prolactin (PRL), and gastrin did not change. Although these results are in general agreement with metabolic effects of other alpha adrenergic blockers already reported, the rise in plasma glucose is at variance with studies performed with phentolamine.

PROLACTIN RELEASE BY INTRAVENOUS CIMETIDINE IN MAN: EVIDENCE FOR A SUPRAPITUITARY LOCUS OF ACTION

In an attempt to identify the sites at which cimetidine stimulates prolactin release, the drug was administered intravenously (6 mg/kg body weight) to healthy subjects under basal conditions, during dopamine infusion (1/μg/Kg‐min for 120 min) and after pretreatment with L‐dopa plus carbidopa (250 plus 25 mg every 6 h for 1 day). The serum prolactin response to cimetidine was abolished by dopamine infusion and almost completely suppressed by L‐dopa plus carbidopa administration. These findings suggest that the drug acts on the central nervous system to stimulate prolactin release. Although the mechanism of this action is unclear, it does not seem to depend on an antidopaminergic effect and may be related to blockade of brain H2 histamine receptors.

Endocrine and metabolic effects of labetalol in man.

The effects of intravenous infusion of the α- and β-adrenoceptor blocking drug labetalol (100 mg over 10 min) on heart rate, blood pressure, and several endocrine and metabolic variables have been evaluated in 12 hypertensive patients (6 men and 6 women). Drug administration was associated with significant lowering of heart rate and systolic and diastolic blood pressure in comparison with a control study performed with saline infusion. Plasma glucose was significantly increased, while no changes were observed in serum-free fatty acids, insulin, C-peptide, and growth hormone levels. Serum prolactin concentration was significantly increased in the whole group, a marked rise occurred in females, while only a trend upward was observed in males. The acute lowering of blood pressure suggests a predominant activity on α-adrenoceptors following intravenous labetalol infusion, although the reduction in heart rate is consistent with the β-adrenoceptor blocking effect of the drug. Although the reason for the increase in plasma glucose is not apparent, it might depend on the rise in norepinephrine levels observed after labetalol. Stimulation of prolactin release by intravenous labetalol is not easily attributable to interference with adrenergic receptors. The mechanism of this action of the drug is presently obscure, although a possible antidopaminergic activity of labetalol might be involved.

Effects of Chronic Prazosin Treatment on the Renin—Angiotensin—Aldosterone System in Man

Abstract: The effects of chronic prazosin treatment (3 mg/day for three weeks) on plasma renin activity (PRA) and plasma aldosterone (PA) levels were evaluated in 12 hypertensive patients, under conditions of metabolic balance. After three weeks of drug administration no significant change occurred in PRA as well as PA levels, with respect to pretreatment values, both in basal conditions and following 2 hours of ambulation. No change was observed in heart rate, while a fall in both systolic (P < 0.02) and diastolic (P < 0.05) blood pressure occurred in supine as well as in deambulation‐stimulated condition. A mild increase in body weight (P < 0.05) and a decrease in serum sodium (P < 0.05) was induced by prazosin treatment. These findings are in keeping with the pharmacologic properties of prazosin, which is a selective blocker of postsynaptic alpha adrenoreceptors and therefore lowers vascular resistance without reflex sympathetic overactivity. The moderate volume expansion after prazosin does not appear to be aldosterone mediated.

Oral glucose tolerance and insulin response after one week's clonidine treatment in hypertensive patients

SummaryAcute clonidine administration is known to induce a significant rise in plasma glucose in man. In order to evaluate the possible effect of prolonged drug treatment on glucose metabolism, paired OGTTs were performed in 12 hypertensive patients (6 with normal and 6 with abnormal glucose tolerance) in basal conditions and following 1-weeks administration of clonidine (0.15 mg every 8 h). Basal plasma glucose and serum insulin concentration as well as glucose tolerance and insulin response to oral glucose did not change in either group after treatment. Although the mechanism(s) mediating the transient hyperglycemic action of clonidine are not fully understood, the present findings indicate that this drug does not exert diabetogenic effects during chronic treatment, and suggest that homeostatic mechanisms may counteract the acute effect of clonidine on glucose metabolism.

Effects of ibopamine on serum prolactin and growth hormone levels in hyperprolactinemic and acromegalic subjects

The effects of oral doses (100, 200, and 400 mg) of a dopamine derivative, ibopamine, on serum prolactin (PRL) and growth hormone (GH) levels were evaluated in hyperprolactinemic patients, some of whom also were acromegalic. There was dose‐related lowering of PRL levels. The highest dose was as effective as 500 mg L‐dopa, although the duration of action was shorter, with a decrease to below 50% of basal PRL values in all patients. Serum GH did not rise in nonacromegalic subjects, but it fell after 400 mg ibopamine in the L‐dopa‐sensitive acromegalic patients. These data suggest, but do not prove, that ibopamine is able to directly stimulate pituitary dopamine receptors.

CLONIDINE AND GROWTH-HORMONE SECRETION

There was no relationship between bone aluminium content, osteoclast number, and marrow fibrosis, in accord with Alfrey and al. who found no correlation between bone aluminium and plasma parathyroid hormone levels. Bone aluminium content was also unrelated to osteoblast number or mineralisation front but, in contrast, it correlated with osteoid volume (see figure). Our observation supports the hypothesis suggested by Parkinson et al .2 and Ward et aU of a relation between osteomalacic bone-disease of dialysis patients and aluminium intoxication. The mechanism(s) by which aluminium accumulation in bone interferes with normal mineralisation are unknown.