Acute effects of clonidine on central and peripheral haemodynamics and plasma renin activity

Brod, J; Horbach, L; Just, H; Rosenthal, J.; Nicolescu, Ramona

doi:10.1007/bf00562506

Cited by 36 publications

(13 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the dosage interval used clonidine produced a dose dependent decrease in blood pressure and the response after the 275 jg dose is in agreement with published findings (Brod, Horback, Just, Rosental & Nicolescu, 1972). No blood pressure increase was observed in our study.…”

Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients.

Frisk-Holmberg¹,

Edlund²,

Paalzow³

1978

Brit J Clinical Pharma

View full text Add to dashboard Cite

1The kinetics of clonidine and its relation to the blood pressure response after single intravenous doses of 75 jtg-275 tig in hypertensive patients were determined. 2 Clonidine disposition could be described by a two compartment open model and pharmacokinetic parameters show a rapid distribution phase of 20-30 min and a mean plasma clearance of 4.6 ml min-' kg-' (75-200 gg). The half-life of the fl-phase was found to be in the range of 7.4-11.4 h.Indications ofdose dependent kinetics were obtained. 3 A dose-dependent decrease in blood pressure was obtained. 4 The maximal reduction in MAP (mean arterial blood pressure) was significantly (P < 0.01) related to plasma concentrations of clonidine. SThe reduction in MAP was always related to plasma concentrations of clonidine (r= 0.88, P< 0.01) when pseudoequilibrium ofdistribution ofthe drug was achieved.

show abstract

Section: Discussionsupporting

confidence: 93%

Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients.

Frisk-Holmberg¹,

Edlund²,

Paalzow³

1978

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Cardiac output is intimately related to venous return, and this emphasizes the need to analyse more closely the effects of clonidine on venous dynamics. Earlier work by Nayler et al (1968) has shown that clonidine does produce venodilatation in dogs, and it has also been shown, in man, to increase venous capacity in the leg, and decrease central venous pressure (Ehringer, 1966;Barnett & Cantor, 1968;Brod et al, 1972). The object of the present study was to investigate the effects of clonidine on the venous return from the hindquarters of cats and dogs in which the input of blood to this region was under the control of the perfusion pump, and was thus independent of drug-induced changes in cardiac output.…”

Section: Introductionmentioning

confidence: 95%

The effect of clonidine on venous haemodynamics in cats and dogs

Bentley

Cullen

Reynoldson

et al. 1986

British J Pharmacology

View full text Add to dashboard Cite

Experiments were undertaken to investigate a possible action of clonidine on venous haemodynamics, using cats and dogs with autoperfused hindquarters. This provided an arterial input to the region independent of cardiac output. Venous capacitance in the hindquarters was indicated by blood flow in the abdominal vena cava, as measured by an electromagnetic flow probe around this vessel. It was found that in both cats and dogs, clonidine given intravenously (5 μg kg−1 i.v.) or into the cisterna magna (1 μg kg−1 i.c.m.) reduced mean arterial pressure and heart rate, but did not decrease hindquarter perfusion pressure. With the exception of dogs given i.v. clonidine, this drug caused a decrease in inferior vena cava (IVC) blood flow and this closely paralleled the hypotensive effect. However, when clonidine was given i.v. to dogs, the decrease in IVC blood flow preceded the hypotension. At the doses used, the reduction in IVC blood flow was larger following i.v. than i.c.m. clonidine in both species, and in all cases, it remained below control levels for at least 30 min, in spite of the constant arterial input to the region. In cats, dose‐response curves were constructed to noradrenaline and adrenaline given into the perfusion circuit (i.a.) before and after clonidine. Following i.v. and i.c.m. clonidine, there was a selective depression of the venoconstrictor actions of the catecholamines, but no change in the arterial pressor action. Radiographic and latex studies in the dog and cat respectively were performed in order to visualize collateral blood flow that could account for the persistent decreases in IVC blood flow. In both species, intraspinal collateral flows were demonstrated which returned blood to the heart after ligation of the inferior vena cava below the renal veins. However, it was not possible to demonstrate radiographically any changes produced by clonidine in the collateral flow because of technical difficulties. These results suggest that clonidine causes a selective reduction in sympathetic tone to the veins that is mediated at least partly by a central action, as well as an expansion of the collateral venous routes. This, together with the selective impairment of venoconstrictor responses to both noradrenaline and adrenaline, may account for the decrease in cardiac output that is most often reported following clonidine.

show abstract

“…Clonidine tends to lower blood pressure by reducing cardiac output and has little or no effect on TPR. 26 '" In contrast, acute therapeutic doses of a-methyldopa that are administered orally, as in the present study, or intravenously, 28 and chronic, oral doses 29 lower blood pressure by reducing peripheral resistance. We did not investigate whether higher oral doses also reduced cardiac output.…”

Section: Discussionmentioning

confidence: 57%

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

Bobik

Jennings²,

Jackman³

et al. 1986

Hypertension

View full text Add to dashboard Cite

SUMMARY We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of a-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after a-methyldopa administration and remained so for the ensuing 7 hours of the study (p < 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p < 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 fimol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by a-methyldopa, and the catecholamine metabolites of a-methyldopa, a-methy lnorepinephrine and a-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of a-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 //.mol to 22.7 fimol (24.7 fimol excreted after placebo). Adding benserazide to the a-methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of a-methyldopa caused little, if any, further antagonism. Our results suggest that short-term oral administration of amethyldopa inhibits norepinephrine release from sympathetic nerves by central mechanisms, and the responses in mean arterial pressure, although small, are consistent with this hypothesis. The reductions in total peripheral resistance also appear to be centrally mediated. pa's action in humans. 6 ' 7 Since a-methyldopa must be metabolized to active metabolites within the central nervous system to exert centrally mediated hypotensive effects, 4 these studies have concentrated on comparing the hypotensive effects of a-methyldopa before and after inhibition of central or peripheral dopa decarboxylase, or both. In general, these methods have not been able to attenuate the cardiovascular effects. Thus, the question of whether the central or the peripheral action of a-methyldopa is the more important in humans is still unanswered.Recently, Zavisca and Wurtman 8 reported that a cocktail of large, neutral amino acids administered intraperitoneally to spontaneously hypertensive rats could partially attenuate the fall in blood pressure produced by a-methyldopa. This effect appeared to be due to a reduction in the amount of a-methyldopa entering the brain.

show abstract

Acute effects of clonidine on central and peripheral haemodynamics and plasma renin activity

Cited by 36 publications

References 11 publications

Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients.

Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients.

The effect of clonidine on venous haemodynamics in cats and dogs

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

Contact Info

Product

Resources

About