Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Swiss Ketanserin Study the antihypertensive efficacy and tolerability of ketanserin (given in 20 or 40 mg doses twice daily) was investigated, after a placebo run-in phase, as monotherapy (n = 68) as well as in combination with either atenolol (100 mg/day) (n = 30) or the potassium-sparing diuretic hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day) (n = 26) in 124 patients with essential hypertension, aged 41 to 82 years. With the addition of ketanserin, diastolic blood pressure fell by 8 +/- 8, 8 +/- 8, and 7 +/- 9 (+/- SD) mm Hg, respectively (p less than 0.05 for all) in the three treatment groups; heart rate remained unchanged or fell slightly. Ketanserin had no effect on body weight, or biochemical variables, including total serum cholesterol and triglycerides, with the exception of a minor increase in apolipoprotein B. Using a patient self-assessment questionnaire (30 items), the addition of ketanserin was associated with a reduction of most of the symptoms encountered in the placebo phase, including sleep disturbances, general feeling of weakness, headaches, nervousness, and fatigue, but there was a tendency toward increases in stuffy nose and dry mouth. In patients older than 60 years, the antihypertensive efficacy of ketanserin was greater, with 59% achieving a diastolic pressure less than or equal to 95 mm Hg versus 45% in the younger patients. This age trend also emerged when ketanserin was combined with either atenolol or the diuretic.
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PMID:Antihypertensive efficacy of ketanserin alone or in combination with a beta-blocker or a diuretic: the Swiss Ketanserin Study. 244 58

We have treated 128 patients aged 40 +/- 9 years (60 males and 68 females), all with essential hypertension (W.H.O. I and II), over a period of 10 yr. The treatment was performed with clonidine at a dose that ranged from 0.150 to 1,200 mg (twice daily). Forty-two patients also received a diuretic (HCTZ 25 mg daily). Mean blood pressure decreased significantly from 169 +/- 10 mm Hg systolic, 107 +/- 3 diastolic to 145 +/- 6 mm Hg (p less than 0.001) 90 +/- 3 mm Hg diastolic (p less than 0.001). Side effects occurred during the first month. These were drowsiness 28%, dry mouth 35%, constipation 13%, dizziness 9%, postural hypotension 2%, and male impotence 3.3% (2/60). Side effects still present after 120 months of treatment were drowsiness 11.7%, dry mouth 26.6%, constipation 14.1%, dizziness 4.7%, and male impotence 1.7% (1/59). The number of patients who discontinued treatment resulting from side effects were 3.34%, all of them within the first 6 months. There were no changes in renal or liver function or in serum electrolytes or lipids. Retinopathy improved in most patients. Electrocardiogram (ECG) improved in 45 patients with LVH. It is concluded that clonidine provided sustained blood pressure control with minimum side effects during 10-year therapy for hypertension.
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PMID:Safety aspects of long-term antihypertensive therapy (10 years) with clonidine. 245 59

The antihypertensive efficacy and tolerability of the 5HT2-receptor antagonist ketanserin was investigated in 188 patients aged 41 to 82 years with mild to moderate essential hypertension. Ketanserin was given as monotherapy (n = 107) as well as in combination with either the diuretic hydrochlorothiazide/amiloride (n = 42) or the betablocker atenolol (n = 39) for 12 weeks. Compared to placebo, ketanserin lowered systolic blood pressure by 11 +/- 16 (SD), 9 +/- 13 and 9 +/- 11 mm Hg (p less than 0.01 for all) and diastolic blood pressure by 9 +/- 10, 10 +/- 9 and 7 +/- 9 mm Hg (p less than 0.001 for all), in the three treatment groups; body weight, serum sodium, potassium, uric acid, cholesterol and triglycerides remained unchanged. The incidence of withdrawals due to unwanted effects was 4% on ketanserin monotherapy, and 12% and 10% on the diuretic/ketanserin and the betablocker/ketanserin combination respectively. Well-being during ketanserin therapy was improved in the older patients in particular; sleep disturbances, daytime fatigue and overall weakness decreased. Ketanserin was well tolerated in combination with the diuretic, whereas in combination with the betablocker the occurrence of dry mouth and stuffy nose was slightly higher. - Ketanserin proved to be an effective antihypertensive drug comparable to other blood pressure lowering agents. It can be combined advantageously with a potassium sparing diuretic or a betablocker. The greater efficacy and tolerability in patients greater than or equal to 60 years qualify ketanserin primarily as an antihypertensive agent for older patients.
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PMID:[Blood pressure lowering action and tolerance of ketanserin in mono- or combination therapy]. 271 Nov 55

The effects of ketanserin on blood pressure and well-being were investigated in 188 patients, aged 41-82 years, with mild to moderate essential hypertension. At entry, 107 were untreated, 42 were taking the diuretic combination hydrochlorothiazide (50 mg/day) plus amiloride (5 mg/day) and another 39 were taking the beta-blocker atenolol (100 mg/day). A single-blind, 4-week placebo run-in period was followed by 12 weeks' oral ketanserin treatment at 20 or 40 mg twice a day. This regimen significantly reduced systolic and diastolic blood pressures in each group. Response rates were greater in patients aged over 60 years. Compared with placebo, sleep disturbances, daytime fatigue and overall weakness decreased during ketanserin treatment (P less than 0.05 for all), but the incidence of dry mouth and stuffy nose increased. In patients older than 60 years there was a greater reduction of complaints than in younger patients. Ketanserin proved effective and well tolerated, improving peripheral circulatory symptomatology, particularly in older patients and those with a good blood pressure response.
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PMID:Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin. 280 91

The serotonin (S2) antagonist, ketanserin was given to 16 patients with essential hypertension on a single-blind basis. Ten patients were treated for 3 years with ketanserin 40-80 mg daily on a once or twice daily regimen. In this group supine blood pressure fell from 164 +/- 4/101 +/- 2 mmHg on placebo to 152 +/- 5/91 +/- 3 mmHg (NS/P less than 0.01) after 3 years of therapy. During treatment, total serum cholesterol remained essentially unchanged while serum triglycerides were significantly reduced. No side-effects were seen except for dry mouth or slight nasal congestion reported by two patients. In six patients regional haemodynamics were assessed by forearm plethysmography. After 3 months of ketanserin, resting vascular resistance was significantly reduced from 58.3 +/- 12 units on single-blind placebo to 47.0 +/- 12 units (P less than 0.005) on single-blind ketanserin, 40 mg twice daily. We conclude that ketanserin is an effective antihypertensive agent during long-term therapy with some beneficial effects on serum lipids. The antihypertensive effect seems to be mediated chiefly by a decrease in vascular resistance.
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PMID:Regional haemodynamics and antihypertensive effects during long-term ketanserin treatment. 293 23

Doxazosin is a new quinazoline derivative that, like prazosin, has selectivity for alpha 1-receptors. A three-way crossover, randomized, open study in 18 patients with essential hypertension was conducted to investigate the clinical pharmacokinetics of 2, 4, and 8 mg doxazosin at steady state. The pharmacokinetics of the initial 2 mg dose was also studied. Doxazosin showed linear pharmacokinetics. Increases in doses from 2 to 8 mg (steady state) produced proportional increases in doxazosin serum levels (maximum plasma drug concentration [Cmax] minimum plasma drug concentration [C min], and O-24-hour area under the curve [AUC(p-24)], whereas half-life (t1/2) (19.4, 18.7, and 19.7 hours, respectively), volume of distribution (3.4, 3.4, and 3.6 L/kg, respectively), clearance from serum (2.2, 2.2, and 2.1 ml/min/kg, respectively), and degree of protein binding (1.2%, 1.0%, and 1.0% unbound, respectively) were dose independent. Similar t1/2 and time to reach peak concentration (tmax) were obtained with 2 mg initial dose and 2 mg steady state. alpha 1-Acid glycoprotein levels were unchanged during doxazosin treatment. Doxazosin lowered supine and standing systolic and diastolic blood pressure. The blood pressure reduction was associated with an increase in heart rate. Peak hypotensive and tachycardic effects occurred 5.7 +/- 0.1 hours after administration, whereas Cmax was achieved at 2.4 +/- 0.7 hours (tmax). Greater decreases in systolic blood pressure and increases in heart rate were seen in standing than in supine position. The reduction in standing systolic and diastolic blood pressure with 8 mg was greater than with 2 mg (P less than 0.05); however, the increases in heart rate were not different. Dizziness, headaches, and dry mouth were the most frequent side effects. This study indicates that doxazosin shows linear pharmacokinetics between 2 and 8 mg and that because of its long t1/2, once-a-day administration should be adequate for the treatment of hypertension.
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PMID:Clinical pharmacology of doxazosin in patients with essential hypertension. 295 Oct 51

More than 5,000 primary-care physicians enrolled more than 22,000 patients with mild to moderate hypertension in a postmarketing study in which guanfacine hydrochloride, a centrally acting antihypertensive agent, was given for 28 days. The objectives of the evaluation were: (1) to obtain broad experience with guanfacine for the management of essential hypertension in a clinical practice setting; (2) to obtain information on patient acceptance of guanfacine, 1 mg HS, for the control of essential hypertension; and (3) to obtain more information on the drug's safety in clinical practice. Patients had to be at least 21 years of age, to be receiving a thiazide-type diuretic, and to have a sitting diastolic blood pressure of 95 to 114 mmHg. Women who were pregnant or lactating or planning to become pregnant during the evaluation were excluded. Blood pressure and heart rate were measured before guanfacine was started and at the completion of the study. Adverse on-therapy events were reported at the return visit. The average blood pressure in the general patient population decreased by 17/12 mmHg, that is, from 164/100 to 147/88 mmHg in four weeks. The magnitude of the reduction was not significantly influenced by age, race, sex, duration of hypertension, or the use of concomitant antihypertensive therapy. Adding guanfacine to another antihypertensive regimen resulted in mean reductions of 11 to 15 mmHg diastolic pressure, and the substitution of guanfacine for another antihypertensive agent resulted in mean reductions of 10 to 11 mmHg diastolic pressure. The most common side effect reported was dry mouth in 6% of patients, followed by dizziness, somnolence, fatigue, headache, and nausea, each reported in fewer than 3% of patients. More than 80% of the participants continued to receive guanfacine after the study. Of the total patient population, 7% discontinued guanfacine because of lack of efficacy, 10% because of side effects, and 3% for other reasons. The results of this large postmarketing study confirmed the results of controlled clinical trials conducted prior to marketing.
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PMID:A postmarketing evaluation of guanfacine hydrochloride in mild to moderate hypertension. 306 7

Guanfacine, an alpha 2-adrenoceptor agonist, was compared with clonidine as step-2 therapy of mild to moderate essential hypertension in a 24-week, double-blind, randomized, parallel evaluation to determine efficacy, safety and occurrence of withdrawal syndrome. During a 5-week period, patients were weaned from current antihypertensives, if any, and stabilized on step-1 therapy with 25 mg of chlorthalidone once a day. Those with a diastolic blood pressure (BP) from 95 to 114 mm Hg while taking chlorthalidone were randomized to treatment. The 2 agents had equal efficacy; 149 of 270 patients treated with guanfacine (55%) and 164 of 276 treated with clonidine (59%) achieved goal diastolic BP of less than or equal to 90 mm Hg. Terminations because of adverse effects were relatively low. Dry mouth (30% of guanfacine and 37% of clonidine groups) and somnolence (21% of guanfacine and 35% of clonidine groups, p less than 0.05) were reported most frequently. Nonsyncopal dizziness was reported in 11% of guanfacine-treated and 8% of clonidine-treated patients. This difference was not statistically significant. To evaluate the occurrence of a withdrawal syndrome in 316 outpatients and 156 inpatients, vital signs were monitored at least twice a day for up to 7 days after the end of therapy. Segmented 24-hour urine studies were performed on inpatients. Abrupt withdrawal of clonidine produced a rapid increase in diastolic and, especially, systolic BP, whereas guanfacine withdrawal produced more gradual increases. The differences were significant over the first 3 withdrawal days. It is concluded that guanfacine is a safe, effective, second-generation alpha 2-adrenoceptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of guanfacine versus clonidine for efficacy, safety and occurrence of withdrawal syndrome in step-2 treatment of mild to moderate essential hypertension. 351 30

Guanfacine, a phenylacetyl-guanidine derivative, is a centrally acting alpha-adrenoceptor agonist, with a mechanism of antihypertensive action similar to that of clonidine. It reduces blood pressure in patients with essential hypertension at least as effectively as clonidine or methyldopa. Like lower doses of clonidine, guanfacine can be given once daily due to its relatively long elimination half-life. Although dry mouth and sedation occur frequently with higher doses of guanfacine, their incidence is lower than with other centrally acting antihypertensives; in addition, other troublesome side effects such as orthostatic hypotension or sexual dysfunction also occur much less with guanfacine than with other centrally acting antihypertensive agents. While a withdrawal syndrome may occur on abruptly discontinuing guanfacine administration, the symptoms are generally mild, and the incidence of withdrawal symptoms appears lower than occurs with abrupt withdrawal of clonidine. Thus, guanfacine is an effective and well tolerated alternative to other centrally acting antihypertensive drugs. Whether its final place in therapy will be as an alternative 'second-line' drug, or as initial monotherapy in patients with mild to moderate hypertension, remains to be clarified in comparative studies with diuretics, calcium antagonists, and beta-adrenoceptor blocking drugs.
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PMID:Guanfacine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. 351 77

This study assessed the antihypertensive efficacy and side effects of clonidine administered transdermally. Twenty-five patients with mild to moderate essential hypertension (seated diastolic blood pressure 95-120 mm Hg with diuretic therapy alone) controlled with oral diuretic plus oral clonidine were enrolled. Transdermal clonidine was substituted for oral clonidine and titrated until adequate blood pressure control (seated diastolic blood pressure less than 90 mm Hg) was attained. At the end of titration, seated morning blood pressure averaged 129/90 +/- 15/5 mm Hg (mean +/- standard deviation) compared to 136/96 +/- 13/7 mm Hg (p less than 0.01/0.001) during oral clonidine administration. Standing morning blood pressure was also lower during transdermal than oral therapy (131/94 +/- 16/5 vs 136/99 +/- 14/7, p less than 0.05/0.001). Afternoon blood pressures (at peak effect of oral dose) were virtually identical during oral and transdermal therapy in both seated and standing positions. Typical side effects of oral clonidine, including dry mouth, drowsiness, and sexual dysfunction, were reduced during transdermal therapy. There was less morning-to-afternoon variability of blood pressure control and plasma clonidine concentrations during transdermal than during oral therapy. One patient left the study because of drowsiness and two because of skin reactions to the transdermal skin patch. Mild transient local skin irritation occurred frequently. Transdermal clonidine plus a diuretic is an effective treatment for mild to moderate essential hypertension, improves compliance and reduces side effects of therapy.
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PMID:Transdermal administration of clonidine: a new approach to antihypertensive therapy. 395 4


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