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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonidine is a centrally active antihypertensive agent effective in the treatment of mild, moderate and severe hypertension, alone or in combination with other drugs. Use of oral clonidine has often been limited by side effects which include dry mouth and drowsiness. Transdermal clonidine was therefore developed as an alternative to oral therapy. Ideally, a drug administered at a constant rate into the systemic circulation should attain steady-state concentrations with less peak-to-trough fluctuation than that associated with intermittent oral dosing. In theory, transdermal administration should thus minimise the adverse effects associated with peak plasma drug concentration, while avoiding the potential for decreased efficacy associated with trough levels. Clonidine has been incorporated into a small, pliable adhesive cutaneous delivery device designed to provide therapeutically effective doses of drug at a constant rate for at least 7 days. The transdermal therapeutic system is a laminate consisting of an external film impermeable to moisture and to the drug, a thin layer of active drug dispersed within a highly drug-permeable matrix, a membrane with a controlled intrinsic permeability regulating the rate of delivery of drug to the skin, and an adhesive coating that attaches the system to the skin surface. The permeation of drug through the skin occurs primarily by diffusion. Application of the clonidine transdermal system to both normotensive and hypertensive subjects has consistently reduced systolic and diastolic blood pressures. Maximum reduction in blood pressure occurs 2 to 3 days after initial application, and is maintained for at least 7 days or until the system is removed. The rate at which clonidine is presented to the skin surface is controlled by the microporous membrane: this rate is the same for all strengths of transdermal clonidine, the amount of clonidine released being proportional to its surface area. Thus, the daily dose is regulated by the area of skin covered. Typically, steady-state plasma concentrations are reached on the fourth day after initial transdermal system application. The lack of dose dependency in half-life and renal clearance estimates emphasise that the transdermal absorption of clonidine is linear. The plasma clonidine concentration produced by a particular transdermal dose varies considerably between individuals as a result of interindividual variation in renal clearance. For this reason, it is recommended that dosages be titrated up from the smallest system (3.5 cm2) until the desired pharmacological effect has been obtained.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of clonidine. 329 68

In renal artery stenosis activation of the renin-angiotensin system elevates blood pressure by direct peripheral effects and probably through stimulation of sympathetic activity, which can be induced by angiotensin-II either centrally or peripherally. In animals specific brain lesions and afferent renal denervation can either attenuate or prevent renovascular hypertension. We investigated the neurogenic mechanisms responsible for hypertension in 21 patients with unilateral renal artery stenosis off drug therapy, by studying the cardiovascular and hormonal effects of Clonidine. The responses to Captopril served as an indicator of the peripheral effects of angiotensin-II. Both oral and intravenous Clonidine lowered blood pressure substantially and for a prolonged period even in patients who had been refractory to multiple antihypertensive drug therapy. Levels of plasma renin activity were unchanged after Clonidine. Plasma noradrenaline levels fell. Pressor responses to infused angiotensin-II were not reduced. These data suggest that Clonidine lowers blood pressure independently of hormonal and peripheral vascular interactions and is consistent with its predominantly central sympatholytic effects. Oral Captopril, unlike Clonidine, had variable hypotensive effects directly related to the basal level of plasma renin activity. The largest reductions were observed in those with the highest level of renin. Our studies indicate that neurogenic mechanisms, probably centrally mediated, have an important and often major role in maintaining hypertension in human renal artery stenosis. These may result from the central effects of angiotensin-II, and/or from increased afferent renal nerve activity, as demonstrated experimentally. The neurogenic components maintaining hypertension in renal artery stenosis are largely dependent on renal ischaemia as revascularisation (by surgery or angioplasty) or nephrectomy, either ameliorates or cures the hypertension in the majority of our patients.
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PMID:Neurogenic components of hypertension in human renal artery stenosis. 331 26

In a six-week multicenter, double-blind comparison study, moxonidine and clonidine HCl were tested in 122 and 30 outpatients, respectively, with mild to moderate hypertension (World Health Organization stage I and II; highest measured diastolic blood pressure, 90 to 115 mm Hg). Each agent reduced systolic and diastolic blood pressure to a similar significant extent: moxonidine, 25.4 and 12.4 mm Hg, respectively; clonidine, 25.3 and 10.0 mm Hg, respectively (P less than .001 vs baseline). The mean individually titrated dose of moxonidine and clonidine HCl was found to be 0.36 mg/d. Clonidine slightly reduced heart rate in patients assuming an upright position by 3 beats/min at the end of dose titration (P = .018), while moxonidine did not. Two patients receiving moxonidine and three patients taking clonidine HCl discontinued therapy because of side effects. However, patients administered clonidine experienced significantly more side effects (53%) compared with a 30% incidence of adverse effects associated with moxonidine (P = .031). The most frequent adverse effect of both agents was dryness of mouth, which was mentioned significantly more often with clonidine (47%) than with moxonidine (20%) (P = .005). Edemas were found in 0.8% and 17% of patients during six-week treatment with moxonidine and clonidine, respectively (P = .001). Accordingly, moxonidine was tolerated significantly better than clonidine (P less than .001) in this parallel comparison study. Moxonidine is as effective as clonidine in monotherapy of mild to moderate essential hypertension and, additionally, neither drug produces clinically important changes in biochemical parameters.
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PMID:Comparison of moxonidine and clonidine HCl in treating patients with hypertension. 331 4

A 74-year-old woman with essential hypertension underwent a course of electroconvulsive therapy (ECT) for the treatment of psychotic depression. Her treatments were associated with delayed and significant hypertension. Clonidine, which controlled her baseline blood pressure, was inadequate in treating her post-ECT hypertension. Acute treatment with hydralazine also failed. Labetalol, a short-acting beta-blocking agent with some alpha-1 blocking activity, worked well both acutely (intravenously) and orally to manage essential and ECT-induced hypertension.
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PMID:Delayed hypertension with electroconvulsive therapy. 337 1

1. In conscious rabbits, intravenous morphine (3 mg/kg) caused hypertension, bradycardia, hyperglycaemia and sedation. These changes were accompanied by large increases in plasma adrenaline and smaller increases in plasma noradrenaline. 2. These effects of morphine were prevented by intravenous naloxone, demonstrating their dependence on stimulation of opiate receptors. 3. Pretreatment with the antihistamines cimetidine and chlorpheniramine enhanced the morphine-induced rise in blood pressure, excluding a role for histamine release in the hypertensive action of morphine. 4. The centrally acting alpha 2-adrenergic agonist clonidine prevented the morphine-induced hypertension and rise in plasma catecholamines, suggesting that these effects are exerted via central pathways. Clonidine alone reduced blood pressure and heart rate and produced hyperglycaemia. 5. alpha-Adrenergic blockade with phenoxybenzamine reduced the increase in blood pressure after morphine, although the increase in plasma catecholamines was augmented. 6. Pentobarbitone anaesthesia prevented the morphine-induced cardiovascular changes, the increase in plasma catecholamines and the hyperglycaemia. 7. These findings indicate, that in conscious rabbits, morphine induces hypertension by stimulation of opiate receptors leading to increased sympatho-adrenal activity. The hyperglycaemia appears to be in response to secretion of adrenaline. These effects probably result from a central action of morphine.
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PMID:Intravenous morphine causes hypertension, hyperglycaemia and increases sympatho-adrenal outflow in conscious rabbits. 340 26

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.
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PMID:Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial. 353 14

The effectiveness of transdermally administered clonidine using Catapres-TTS patches applied once a week was assessed in the control of mild to moderate hypertension by 16 general practitioners in 135 subjects. Following two weeks on placebo patches, subjects with mean seated diastolic pressures 90 to 104 mmHg were titrated to one, two or three patches and blood pressure responses measured at monthly intervals for three months. Satisfactory response of blood pressure to 90 mmHg or lower was obtained in 85% of patients who completed the maintenance phase; in 20 patients whose blood pressure responses did not reach 90 mmHg, a significantly higher blood pressure (mean 158/103 mmHg) occurred at entry into the trial (145/96 mmHg). Withdrawal from the trial was mainly for reasons of inadequate blood pressure control (15%) or localised skin reactions (15%). Dryness of the mouth was the only systemic side effect encountered with significant frequency and resulted in the withdrawal of three patients. Localised skin reactions were encountered in 51% of subjects, in the majority these were mild and subjects elected to continue with transdermal clonidine because of the convenience of once a week administration. Severe or generalised skin reactions were not encountered. Serum biochemical measurements, including serum lipid levels, remained unaltered. Transdermal clonidine therapy provided satisfactory blood pressure control in the majority of subjects and apart from the localised skin reactions which were largely of nuisance value, proved safe and acceptable to patients.
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PMID:A community-based trial of transdermal antihypertensive therapy with clonidine (Catapres-TTS). 354 2

In conscious rats with normal arterial blood pressure or with spontaneous or DOC induced hypertension, effects of drugs increasing (cycloserine, ethanolamine-o-sulphate, piracetam, chlordesmethyldiazepam) or depressing (bicuculline, Ro 15-1788, PK 11195) GABAergic reactivity were evaluated on the arterial hypotension and sinus bradycardia induced by clonidine. Clonidine was administered orally by gastric gavage (0.1-1 mg/kg). Pretreatment with cycloserine, ethanolamine-o-sulphate, piracetam or chlordesmethyldiazepam increased the hypotension and sinus bradycardia induced by clonidine. On the contrary, pretreatment with bicuculline or Ro 15-1788 reduced the cardiovascular effects of clonidine. These results suggest that the GABAergic system is involved in cardiovascular effects of clonidine in normotensive and hypertensive rats.
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PMID:Participation of GABAergic mechanisms in the hypotensive and bradycardic effects of clonidine: experimental study in conscious normotensive and hypertensive rats. 368 66

We have studied the efficacy of clonidine hydrochloride administered transdermally once a week for 9 to 15 weeks in 12 patients with mild to moderate hypertension. Clonidine reduced both supine and standing blood pressures on average, but only 8 subjects were responders, i.e. had a decrease in supine diastolic blood pressure to below 90 mm Hg or more than 10% from baseline. Supine heart rate was unchanged, but in the responders the orthostatic increase in heart rate was reduced by clonidine from baseline (p less than 0.05). Moreover, in all the patients the change in the orthostatic increase in heart rate was correlated with the change in supine diastolic pressure (p less than 0.05). Brachial artery blood flow, forearm arterial compliance, vascular resistance, and venous tone were not affected by clonidine. Thus, transdermal clonidine reduced blood pressure, probably by a baroreflex-mediated effect, but did not affect the vasculature of the forearm.
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PMID:The efficacy of a transdermal formulation of clonidine in mild to moderate hypertension and its effects on the arterial and venous vasculature of the forearm. 369 4

The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus 51Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 micrograms) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79 +/- 13/8 to 104/68 +/- 9/7 mmHg (p less than 0.01), urinary albumin excretion rate from 68 (31-369) to 46 (6-200) micrograms/min (median and range) (p less than 0.01), and fractional clearance of albumin in all patients (median 29%) (p less than 0.01). Glomerular filtration rate was 110 +/- 11 before and 106 +/- 13 ml/min/1.73 m2 after clonidine injection. The blood glucose concentration was 15 +/- 4 mmol/l before and 14 +/- 5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.
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PMID:Acute reduction of arterial blood pressure reduces urinary albumin excretion in type 1 (insulin-dependent) diabetic patients with incipient nephropathy. 371 12


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