Search PubMed⌕ Search

Biomedical subjects

M D Coleman

Publications and source records attributed to M D Coleman.

68 records · Page 4Linked to original sources
PubMed1984

Effect of antihypertensive therapy on sympathetic nervous system activity in patients with essential hypertension.

The sympathetic nervous system (SNS) plays a major role in blood pressure regulation. Although the exact relationship of the SNS to the etiology of hypertension remains undetermined, many of the agents used to treat hypertension interfere with this system. Clonidine, methyldopa, guanethidine, and reserpine decrease SNS tone whereas hydralazine, minoxidil, and hydrochlorothiazide increase it. Most evidence suggests that beta-adrenergic blocking agents decrease SNS activity. The effect of prazosin and captopril on the SNS requires further study. The appropriate use of these antihypertensive agents requires a knowledge of their sites of action and the physiological reflexes they induce. Efficacy, toxicity, and effective drug combinations can be predicted based on their mechanism of action and effect on SNS activity.

Antihypertensive Agents↗
PubMed1983

Fenfluramine lowers plasma norepinephrine in overweight subjects.

The effect of fenfluramine on sympathetic nervous system activity was determined in 12 normotensive, obese men. Supine plasma norepinephrine (NE) concentrations decreased (p less than 0.001) from pretherapy levels (298 +/- 39 pg/ml) after one (166 +/- 30 pg/ml) and four weeks (171 +/- 28 pg/ml) of fenfluramine (60 mg daily). Fenfluramine did not alter the sympathetic nervous system responses to orthostasis or exercise. Fenfluramine-induced decreases in heart rate (72 +/- 3 to 67 +/- 4 beats/min, p less than 0.01) and mean arterial blood pressure (90 +/- 2 to 81 +/- 2 mmHg; p less than 0.005) were observed after only one week of therapy despite no significant change in body weight. We conclude that fenfluramine may be a useful agent in the treatment of patients with sympathetic hyperactivity. The effects of fenfluramine on given subsets of patients and control subjects are also defined.

Adult↗
PubMed1983

Effect of clonidine on sympathetic nervous system activity in patients with essential hypertension.

This study analysed the effects of both seven and 30 days of treatment with clonidine on heart rate, blood pressure (BP), plasma norepinephrine (NE) levels and dopamine-beta-hydroxylase (DBH) activity at rest and after standing in seven patients with essential hypertension. The patients and 10 age-matched normotensive control subjects were evaluated under medication-free baseline conditions; the hypertensive patients were then given clonidine 0.1 mg twice daily. Baseline plasma NE and DBH levels were similar between the groups. Seven and 30 days of clonidine therapy reduced blood pressure (p less than 0.001) and NE concentrations (p less than 0.05) significantly. Clonidine did not effect the percent increase in NE induced by standing and was not associated with orthostatic hypotension. The blood pressure lowering effects of clonidine appear related to the centrally mediated and/or direct suppression of peripheral noradrenergic activity, indicating the utility of clonidine in cases of hypertension were the sympathetic nervous system (SNS) is hyperactive. Clonidine may also prove especially useful in cases where the initial pharmacotherapy (such as a diuretic) causes activation of the SNS.

Adult↗
PubMed1980

Fenfluramine potentiation of antihypertensive effects of thiazides.

Hydrochlorothiazide, a drug which is often initially prescribed for mild to moderate hypertension, failed to lower blood pressures in 9 of 43 patients but concomitantly elevated plasma norepinephrine (NE) levels in all patients with hypertension. The 9 obese hydrochlorothiazide-resistant patients were then given fenfluramine, an anorectic, in addition to the thiazide. They were reevaluated after 2 and 5 wk, at which times there were reductions in blood pressures and marked reductions in the plasma NE levels which had been elevated by the hydrochlorothiazide. Since iatrogenic sympathetic activation seems undesirable in treating hypertension, fenfluramine may be useful in obese thiazide-resistant hypertensive patients when used in combination with a thiazide diuretic.

Antihypertensive Agents↗
PubMed1979

Hydrochlorothiazide-induced sympathetic hyperactivity in hypertensive patients.

Hydrochlorothiazide-induced diuresis and natriuresis is considered to be responsible for the antihypertensive effect of this drug. After short-term treatment there is decreased cardiac output and increased peripheral resistance which we have found to be attended by increased plasma norepinephrine (NE) levels. After longer treatment cardiac output returns to normal and peripheral resistance declines. At this time, plasma NE levels remain elevated, indicating that peripheral resistance reduction is not a consequence of a reduction of the elevated level of sympathetic activity. These results provide a rationale for the combined use of diuretics and drugs which diminish noradrenergic activity in the treatment of hypertension.

Adult↗
PubMedDate not supplied

The disposition of pyrimethamine base and pyrimethamine pamoate in the mouse: effect of route of administration.

We have investigated the plasma pharmacokinetics and mass fate in mice, of pyrimethamine administered as either the base or as the poorly soluble pamoate salt, in each case by the intraperitoneal (i.p.) and subcutaneous (s.c.) routes. Following the administration of pyrimethamine base (i.p. and s.c.) and pyrimethamine pamoate (i.p.), maximum measured plasma levels of pyrimethamine were attained within 1 h, before declining monoexponentially. There was no significant difference between these three groups in the clearance (0.29 +/- 0.05, 0.30 +/- 0.03, 0.26 +/- 0.05 ml min-1), elimination half-life (4.5 +/- 0.5, 4.8 +/- 0.8, 4.9 +/- 0.5 h) and AUC (19.4 +/- 4.4, 17.3 +/- 2.2, 21.1 +/- 4.4 micrograms.h ml-1). By contrast, after s.c. dosage of pyrimethamine pamoate, drug absorption was significantly delayed, maximum plasma levels being reached after 4 h, these levels being approximately one-third of those in the other three groups. Absorption was however complete, as the values for AUC and clearance were not significantly different from the other groups. The pattern of faecal and urinary elimination of 14C radioactivity was unaffected by either dose site or formulation of pyrimethamine. The majority of the dose (44.5-64.2 per cent) was eliminated in the faeces suggesting extensive biliary excretion. Localization of 14C radioactivity in the major organs was negligible in all groups. Following each dose, between 85 and 98 per cent of the dose was accounted for. These studies indicate that of the four treatment groups only pyrimethamine pamoate on s.c. administration demonstrates a sustained release action from the dose site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Primaquine disposition in the isolated perfused rat liver: effect of mefloquine induced bile flow reduction.

The disposition of primaquine (0.75 mg, 5 microCi) has been investigated in the isolated perfused rat liver (IPRL) preparation alone and concurrently with mefloquine. In both groups, primaquine concentrations declined exponentially. There were no significant differences between the respective groups in the half-lives (2.5 +/- 1.5, 2.2 +/- 1.1 h), AUCs (0.43 +/- 0.14, 0.372 +/- 0.096 microgram.h ml-1), clearances (19.0 +/- 5.4, 21.1 +/- 4.2 ml h-1), and apparent volume of distribution (78.9 +/- 28.1, 76.2 +/- 31.7 ml). In the presence of mefloquine, total bile production was significantly reduced (1244.5 +/- 317.1 microliters) compared with primaquine alone (1621.5 +/- 174.2 microliters). Hence, although significantly less radioactivity ([3H]) was eliminated in bile in the presence of mefloquine (30.0 +/- 7.9 per cent versus 39.9 +/- 3.6 per cent) there was no significant difference between the groups in [3H]/microliters bile eliminated. Significantly more [3H] was recovered from the livers of the mefloquine/primaquine group. This was underlined by the significantly greater proportions of [3H] recovered from the 10,000 g pellet, 10,000 g supernatant and 105,000 g supernatant in the presence of mefloquine compared with primaquine alone. Hence, it appears mefloquine had little or no direct action or primaquine metabolism, but significantly reduced bile production.

Animals↗
PubMedDate not supplied

1H nuclear magnetic resonance study of metronidazole metabolism by perfused rat liver.

High-resolution 1H nuclear magnetic resonance (NMR) spectroscopy at 300 MHz has been used to monitor the metabolism of metronidazole by the perfused rat liver. Samples of perfusate removed at various times during the perfusion show resonances from metronidazole and its major metabolites, as well as those from organic metabolites released from the liver. The major metabolite of metronidazole is shown to be its glucuronide conjugate. Metronidazole metabolism and glucuronide production are both stimulated in livers from rats pretreated with phenobarbitone.

Animals↗
PubMedDate not supplied

Age-dependence of hypertensive-normotensive differences in plasma norepinephrine.

We compared venous plasma norepinephrine (NE) concentrations in 191 resting, supine patients with essential hypertension and 129 normotensive controls. Among normotensives, plasma NE increased significantly with age, but among hypertensives, no age-related increase occurred, due to relatively high NE values among young hypertensives. When patients and controls less than 40 years old were considered, hypertensives showed significantly higher plasma NE than the controls (317 vs 245 pg/ml, t = 3.15, p less than 0.01); but above the age of 40 years, no significant hypertensive-normotensive difference was obtained. These results, predicted by recent literature reviews, help to resolve the persistent controversy about sympathetic neural activity in essential hypertension, since such activity appears to be abnormal mainly in young patients. The data are consistent with increased sympathetic nervous system activity in the early stages of essential hypertension.

Adult↗
PubMedDate not supplied

Prestructural determinants in a case of phobia.

Questions of genesis, dynamics, and treatment techniques, in what is hypothesized as the first developmental layer of agoraphobic or pan-anxious symptoms, are considered. In the patient described it was concluded that this layer of anxiety came from many inadequate ego functions brought about by a mother who could not (for reasons speculated about in her history) tolerate autonomous functioning in this child. This mother-child reality shaped the course of the patient's first four years of therapy. During this period of treatment there was more material that lent itself to reconstruction of her real world as perceived by the developing ego, while there was a paucity of fantasy material available. It is suggested that the symptom state called agoraphobia resulted from continuous stimulation since infancy from a mother making dyadic functioning appear imperative for the patient's emotional equilibrium. In similar cases, the initial phase of therapy should focus on reconstructions and clarifications of past and present dyadic relationships. This, as well as other technical interventions to aid development of attenuated ego functions, appears to be necessary as the initial and crucial aspect of therapy.

Adult↗