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

The clinical pharmacology of clonidine has been studied using a sensitive specific method of drug analysis and quantitative measures of cardiovascular and other drug effects. The plasma concentration effect relationship for dry mouth and sedation is log linear until a maximum effect is achieved. The relationship of plasma level to hypotensive effect in man and animals shows a positive correlation over a narrow concentration range up to 1.5--2.0 ng/ml. At higher plasma levels a reversal of hypotension occurs with hypertension at concentrations over 10 ng/ml. This "therapeutic window" may reflect actions of clonidine on alpha receptors in the brain stem which lower blood pressure counteracted by peripheral effects of vascular alpha receptors which causes hypertension. Information on the pharmacokinetics and dynamics of clonidine can assist in optimising this form of antihypertensive therapy.
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PMID:The clinical pharmacology of clonidine: relationship between plasma concentration and pharmacological effect in animals and man. 741 73

A 12-week crossover study was carried out in 24 patients with chronic hypertension to compare the effect of clonidine given in a sustained-release form with that of a standard tablet. A long-term study (48 weeks) was performed immediately afterwards in the same patients to determine the effectiveness and acceptability of the sustained-release form in maintenance therapy. Using approximately the same dose of clonidine (300 or 450 micrograms/day for the standard tablet, 250 or 500 micrograms/day for the sustained-release form), no significant difference in hypotensive effect was found between the two forms of administration. The sustained-release form, however, was preferred by all patients because of lesser side-effects. During the long-term follow-up, the hypotensive effect was fully maintained in all patients. Side-effects which occasionally occurred at the start of the study, in particular dry mouth and a slight sensation of dizziness, subsided in the course of therapy. Laboratory investigations and clinical findings gave no indication of any chronic toxic changes.
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PMID:Treatment of hypertensive out-patients with a sustained-release dosage form of clonidine: a comparison with standard tablet therapy and long-term follow-up study. 742 5

Although essential hypertension is usually defined as a hemodynamic disorder, it is expressed differently among individuals and varies during progression of the disease state. Therefore, various types of treatment can be envisioned. The use of selective I1-imidazoline-receptor agonists to modulate I1-imidazoline receptors involved in the central regulation of blood pressure has led to the introduction of a novel class of centrally acting antihypertensive drugs. Moxonidine, a representative molecule of this class, dissociates between a 10% alpha 2-adrenoceptor-agonist action linked with side effects such as fatigue or dry mouth, and a 90% specific antihypertensive action resulting from its selective agonistic action at I1-imidazoline receptors. Clinical experience is based on more than 2,000 patients and volunteers, and long-term efficacy has been demonstrated in about 500 patients who received a daily dose of moxonidine 0.2-0.4 mg. Moxonidine produces a pronounced reduction in peripheral vascular resistance without reflex tachycardia, accompanied by reduced plasma norepinephrine concentration and plasma-renin activity. Cardiovascular responses to exercise and standing remain nearly normal, and serious or life-threatening side effects, particularly the sympathetic overactivity that can occur on sudden withdrawal of other centrally acting agents, are never observed. In addition, moxonidine behaves neutrally with respect to plasma levels of cholesterol, potassium and glucose, glucose and lipid metabolism, and renal function, and can be administered without complication to patients with asthma or certain other diseases. Studies with magnetic resonance imaging have shown that moxonidine significantly reduces left ventricular mass, an indicator of left ventricular hypertrophy (LVH), within a 6-month treatment period, an effect that coincided with decreased plasma concentrations of catecholamines and renin. Comparisons between moxonidine and other well-established antihypertensive drugs such as nifedipine, atenolol, or angiotensin-converting enzyme inhibitors showed equal effectiveness in lowering blood pressure, whereas the adverse events profile always favored moxonidine. Considering its efficacy, safety, and specific effects (e.g., its ability to reduce LVH), moxonidine meets the criteria satisfied by other currently prescribed antihypertensive drugs. Because of its especially favorable benefit-to-risk ratio, moxonidine should be recommended as first-line treatment of hypertension and may also be useful in treating related problems such as LVH, coronary artery disease, and ventricular premature beats.
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PMID:I1-imidazoline-receptor agonists in the treatment of hypertension: an appraisal of clinical experience. 753 26

The influence of the sympathetic nervous system on blood pressure control was impressively demonstrated in 1940 by bilateral excision of sympathetic nerve fibers. Thereafter, the first generation of drugs lowering blood pressure by central modulation of the sympathetic outflow through alpha 2-adrenoceptor for stimulation, such as alpha-methyldopa, guanabenz, clonidine, and guanfacine, were marketed. However, these compounds were often tolerated poorly, because they caused orthostatic hypotension, sedation, tachycardia or bradycardia, dry mouth, and reduced cardiac output. The mode of action of the second generation centrally acting antihypertensive drugs moxonidine and rilmenidine is different from that of the first generation compounds (e.g., clonidine). Contrary to clonidine, the newer drugs bind more selectively to I1-imidazoline receptors rather than to alpha 2-adrenoceptors where first-generation drugs act. The high affinity and selectivity of these two drugs for this recently discovered new receptor class make it possible to discriminate between I1-imidazoline receptor-mediated blood pressure lowering, on the one hand, and alpha 2-adrenoceptor-mediated side effects, on the other. Discrimination of the two effects was substantiated either by studies using moxonidine alone or in interaction experiments with I1-imidazoline receptor or alpha 2-adrenoceptor antagonists. The high selectivity of moxonidine at the I1-imidazoline receptor allows discrimination between alpha 2-adrenoceptors and I1-imidazoline receptors and is reflected in man by the relatively low incidence of adverse drug events during moxonidine treatment. Concentration of endazoline, a specific mediator of I1-imidazoline receptors, is elevated in some patients with essential hypertension. Modulation of I1-imidazoline receptors by moxonidine could be interpreted as antagonism with regard to the endogenous agonistic effect of the endogenous "transmitter" endazoline. On the other hand, moxonidine acted directly as an agonist at the putative I1-imidazoline receptor. Therefore, to clear the ground, characterization as well as physiological function of the mediator for imidazoline receptors seems essential. The therapeutic relevance of using drugs selective for I1-imidazoline receptors for blood pressure reduction in hypertensive patients is substantiated by the finding that in human rostral ventrolateral medulla (RVLM), which is essential in central blood pressure regulation, the relation between alpha 2-adrenoceptors and I1-imidazoline receptors is about one to ten (1:10). Reduction of a long-lasting sympathetic overdrive may avoid the deteriorating effects on the heart and peripheral circulation. These recent findings give a rational explanation for the very low incidence of sedation and the absence of respiratory depression, orthostatic hypotension, and rebound hypertension that banned the former central acting antihypertensive drugs from first-line treatment despite the advantages of central mediated blood pressure control.
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PMID:Why imidazoline receptor modulator in the treatment of hypertension? 767 85

Centrally acting antihypertensive drugs are recognized to be safe and effective treatment for high blood pressure. Centrally mediated side effects, such as sedation, are commonly dose- and treatment-limiting events. Imidazoline-preferring receptors, while functionally similar to alpha 2 adrenoceptors, are distinguishable not only on the basis of in vitro radioligand binding but also in vivo in terms of side effects. Drugs with an imidazoline structure lower blood pressure but are less likely to impair psychomotor function. A placebo-controlled study compared moxonidine 0.1 mg with clonidine 0.1 mg orally in nine normal subjects. Both active drugs lowered blood pressure compared to placebo (clonidine more than moxonidine). However, psychomotor function and self-scored sedation and dry mouth were significantly affected only by clonidine. In a long-term (4 weeks) double-blind cross-over study in essential hypertension, rilmenidine was well tolerated and had similar effects to those of atenolol on erect and supine blood pressure. Rilmenidine had no effect on a wide range of autonomic and psychomotor tests or on responses to mental or physical stress. Atenolol, by contrast, had the predicted effects of a beta adrenoceptor antagonist on heart rate during exercise and the Valsalva maneuver. Imidazoline-preferring drugs offer a new and realistic approach to antihypertensive therapy with blood pressure reduction not limited by marked sedation within the therapeutic dose range.
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PMID:Clinical pharmacology of drugs acting on imidazoline and adrenergic receptors. Studies with clonidine, moxonidine, rilmenidine, and atenolol. 767 87

The impact of antihypertensive medications on the quality of life of elderly hypertensive women has rarely been systematically evaluated in large clinical trials using drugs from the new generations of pharmaceutic preparations. We carried out a multicenter, randomized double-blind clinical trial with 309 hypertensive women aged 60 to 80 years to assess effects of atenolol, enalapril, and isradipine on measures of quality of life over a 22-week period. The patients had mild to moderate hypertension. Hydrochlorothiazide was added to treatment if monotherapy was inadequate in lowering blood pressure. At the conclusion of the trial the three drug groups did not differ in degree of reduction of diastolic blood pressure or in supplementation with hydrochlorothiazide. Over the 22-week trial, linear trend analysis showed no differences between the treatment groups in change from baseline on quality of life measures of well-being, physical status, emotional status, cognitive functioning, and social role participation. Regarding each of 33 physical side effects over the 22 weeks, we found no general difference between atenolol, enalapril, and isradipine groups on measures of change in distress over symptoms except for enalapril patients who worsened in distress over cough (P = .001) and atenolol patients who worsened in distress over dry mouth (P = .014). Centering on three medications that are relatively new additions to the armamentarium for blood pressure control, the findings underline the increasing opportunities for the physician to select drugs that can control blood pressure while maintaining the quality of life of elderly hypertensive women.
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PMID:Effects of antihypertensive medications on quality of life in elderly hypertensive women. 803 48

The long-term safety and efficacy of transdermal clonidine (C-TTS) was evaluated in 102 patients with mild to moderate hypertension over a mean treatment period of 4.9 +/- 1.4 years. C-TTS size 1 was used by 29.4%, C-TTS size 2 by 35.3%; in 35.3% of the patients a diuretic agent was given in addition. The baseline blood pressure of 168/100 mmHg was reduced to 150/85 mmHg at the end of titration and remained stable during long-term treatment. After 5 years seated blood pressure was 147/83 mmHg. Systemic side-effects, e.g. 4.9% dry mouth, were reported mainly during the first month. Transient local side-effects occurred mainly between weeks 4-26, thereafter the incidence clearly diminished and did not cause any withdrawal due to skin reactions from 1 year up to 6.5 years. Overall the long-term transdermal clonidine treatment was highly accepted by the patients, was effective and was well tolerated.
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PMID:Long-term (5 year) experience with transdermal clonidine in the treatment of mild to moderate hypertension. 819 26

Cardiovascular diseases are the leading causes of death in the United States, with hypertension being amongst the most prevalent of the cardiovascular risk factors. Improvement of hypertension management has, in consequence, received much attention. Extensive pre- and post-marketing experience with the transdermal formulation of clonidine marketed in the USA in the mid-1980s has now been accumulated. Transdermal clonidine is effective as monotherapy in mild-moderate hypertension, and in combination with diuretics, calcium antagonists and ACE inhibitors in more resistant cases. It controls blood pressure throughout the 24-h circadian cycle. It is effective and generally well-tolerated in adolescents, the elderly, blacks, diabetics, and subjects with chronic renal insufficiency. It has been used perioperatively and for suppression of adrenergic symptoms in subjects withdrawing from addicting substances. In comparison with oral clonidine, transdermal clonidine reduces the incidence and severity of such symptomatic side-effects as dry mouth, drowsiness, and sexual dysfunction. Minor skin reactions occur at the site of application of the transdermal patch with moderate frequency. Adherence to transdermal clonidine therapy is high, and patients commonly prefer it to oral therapy. Transdermal administration of clonidine is a useful therapeutic advance in the long-term management of hypertension.
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PMID:The USA experience with the clonidine transdermal therapeutic system. 819 27

Large fluctuations of blood pressure are commonly experienced by hypertensive, chronic hemodialysis patients. Many patients hold anti-hypertensive medication immediately prior to dialysis to prevent intradialytic hypotension. Weekly dosing of continuously released antihypertensive agents may result in better blood pressure control than conventional daily dosing. To evaluate the effect of weekly transdermal clonidine on this problem, we compared intra- and interdialytic blood pressure control and side effects during six weeks of transdermal clonidine monotherapy and six weeks of conventional oral antihypertensive treatment in nine stable chronic hemodialysis patients. Since transdermal clonidine is recommended for mild to moderately severe hypertension and since clonidine is excreted by the kidneys and removed by hemodialysis, we also evaluated blood pressure control and clonidine levels while utilizing high-dose transdermal clonidine, up to 0.12 mg per week. Intradialytic blood pressure was monitored twice weekly during the weeks 3-6 of transdermal clonidine and conventional therapy. Twenty-four hour blood pressure was monitored weeks 3 and 6 of each study phase. Plasma clonidine levels were measured by HPLC in 11 patients. Transdermal clonidine monotherapy failed to adequately control blood pressure in 6 of 21 chronic dialysis patients with moderate to severe hypertension. No significant difference in intra- or interdialytic blood pressure control or side effects (including dry mouth or thirst) was found comparing conventional to transdermal clonidine therapy. While not statistically different, heart rate was lower during transdermal clonidine therapy compared to conventional therapy, especially at very high doses. Despite a mean hemodialysis clearance of clonidine of 59.2 +/- 7.8 ml/min, clonidine levels remained therapeutic beyond one week.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Use of transdermal clonidine in chronic hemodialysis patients. 842 5

Fifty patients suffering from depression were treated wigh mianserin in monotherapy. ICD-9 and DSM-III criteria for depression were used. Patients were divided into four groups--with monopolar depression (28 patients), bipolar depression (8 patients), organic depression (10 patients), neurotic depression (4 patients). The intensity of psychopathological symptoms of depression was established using the Hamilton Depression Rating Scale (HDS) on the 7th, 14th and 28th day of the treatment. The antidepressant action of mainserin was evident already on the 14th day of treatment. Mianserin proved to be most effective in endogenous bipolar depression group and neurotic depression group (70% reduction in the score obtained on the HDRS). Mianserin was well tolerated by most patients. Most frequent side effects observed were: hypertension (8 patients), feeling of anxiety (10 patients), constipation (8 patients), tachycardia (6 patients), dry mouth (3 patients).
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PMID:[Mianserin efficacy in the treatment of depression]. 872 45


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