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

Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients.
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PMID:[Cardiac interactions between ketanserin and the calcium antagonist nifedipine]. 127 88

The cardiovascular responses induced by intracerebroventricular or intravenous administration of ketanserin in normotensive rats were evaluated. Ketanserin, which is an antagonist at 5-HT2 receptors, when microinfused into the third cerebral ventricle, did not induce significant cardiovascular effects, except for a slight and transitory hypotensive response after the microinfusion of the highest dose (200 micrograms). However, at doses which were unable to affect directly blood pressure or heart rate, ketanserin, microinfused into the same site, antagonized the pressor response induced by peripheral administration of methoxamine, an alpha 1-adrenoceptor agonist. Furthermore, peripheral administration of ketanserin produced dose-dependent hypotension and bradycardia and antagonized the pressor effect of an intravenous bolus injection of methoxamine. In conclusion, the present experiments confirmed the ability of ketanserin to produce cardiovascular effects when administered peripherally and provides evidence for an involvement of ketanserin-sensitive receptors in the brain in the regulation of phasic responses during experimentally induced hypertension.
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PMID:Inhibition by intraventricular microinfusion of ketanserin of the cardiovascular responses to peripheral administration of methoxamine in rats. 165 88

Ketanserin, an antagonist of 5-HT2-serotonergic and alpha 1-adrenergic receptors, has come into use for the therapy of mild to moderate arterial hypertension. Quite recent observations have shown changes in transmembrane sodium (Na) transport after the acute administration of high doses of this drug to normal subjects. It is well known that some of these transport systems have an altered activity in essential hypertension. We evaluated the effects of long-term (3 months) administration of ketanserin (40-80 mg/day) on Na and potassium (K) intracellular concentrations and transmembrane fluxes in red blood cells (RBCs) from 12 essential hypertensive patients. In addition the present study describes the in vitro effects of two different concentrations of the drug (5 x 10(-8) and 5 x 10(-7) M) on erythrocytes in normal subjects. In the first study, both systolic and diastolic blood pressure were significantly lowered by the treatment with ketanserin (from 165/103 to 143/89; p less than 0.001). Na and K intraerythrocyte concentrations fell markedly during ketanserin administration (both p less than 0.001). A marked decrease in Na,K-pump activity (p less than 0.001) and an increase in Na,lithium(Li)-countertransport function (p less than 0.001) were observed. Na outward cotransport, Na leak, and K leak were not modified by the therapy. Direct correlation was found between the fall in mean blood pressure and in Na and K intraerythrocyte concentration (respectively, p less than 0.01 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ketanserin on transmembrane sodium transport in erythrocytes. 168 23

Ketanserin, an S2 antagonist, has been shown to be an effective antihypertensive drug. Carefully controlled clinical trials have demonstrated that ketanserin is as effective as both metoprolol and thiaside diuretics in reducing blood pressure. However, unlike the beta-blocking drug metoprolol and the diuretics, the response rate to ketanserin is significantly greater in older patients, reflecting perhaps the greater vasoconstrictor effects of 5-hydroxytryptamine in patients with atherosclerotic disease. This enhanced vasoconstrictor response to serotonin in elderly patients may be matched by an increased effect on platelet aggregation, which is also blocked by ketanserin. There is very suggestive evidence from the PACK study that ketanserin may reduce vascular thrombotic episodes in patients with extensive atherosclerosis. This unique characteristic, combined with effectiveness as an antihypertensive agent, makes ketanserin a particularly useful drug in the treatment of elderly patients with hypertension and vascular disease.
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PMID:Age-related effects of 5-HT2 antagonists. 171 70

The haemodynamic effects of ketanserin were studied consecutively in seventeen patients in the intensive care unit following coronary artery bypass grafting. Hypertensive patients (Group 1, systolic blood pressure (SBP) greater than or equal to 150 mmHg following discontinuation of nitroprusside, n = 10) received intravenous ketanserin 10 mg and infusion of 0.1 mg.kg-1.hr-1 with additional boluses as required to maintain SBP less than or equal to 130 mmHg for one hour. Non-hypertensive patients (Group 2, SBP less than 150 mmHg, n = 7) received a 5 mg bolus and the same infusion. Ketanserin significantly decreased arterial blood pressure (P less than 0.001) in all patients in Group 1. Heart rate was decreased but not significantly. Cardiac index, systemic and pulmonary vascular resistance and pulmonary shunt fraction were not significantly altered from pre-ketanserin values when blood pressure was controlled with nitroprusside. Normotensive patients in Group 2 did not show any undesirable hypotension or significant haemodynamic changes. Mean nitroprusside dose requirements following ketanserin therapy were significantly reduced by 91.6% in Group 1 and 78.4% in Group 2 (P less than 0.05). Ketanserin is effective in treating hypertension following coronary artery bypass grafting with an advantage of lack of reflex tachycardia.
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PMID:Haemodynamic effects of ketanserin following coronary artery bypass grafting. 176 2

The chronic antihypertensive effect of the combination of ketanserin (KET) 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg was evaluated in 20 patients with arterial hypertension of mild to moderate degree. After a 2-week wash-out period, patients were prescribed a single oral dose of KET 40 mg or HCTZ 25 mg in a randomized order at 2-day intervals and blood pressure and heart rate were measured during the following 24 hrs by an automatic recorder. Thereafter patients were given the combination of KET 40 mg + HCTZ 12.5 mg for 6 weeks and 24 hrs blood pressure was recorded after the first dose of the combination and at the end of treatment. Ketanserin induced a significant fall in systolic and diastolic pressures for up to 8 hrs; thiazide did not induce any change in these parameters. The combination of KET + HCTZ in the acute study reduced significantly systolic (SBP) and diastolic (DBP) blood pressures for up to 10 hrs. After 6 weeks of treatment with KET + HCTZ, blood pressure showed a further fall at each time period and was normalized (BP greater than 160/80 mmHg) for 8 hrs after dosing. The results of this study indicate that once daily oral administration of the combination of KET 40 mg + HCTZ 12.5 mg in mild to moderate primary hypertensives significantly reduces blood pressure over 24 hrs. Fairly good control of BP, i.e. BP less than 160/90 mmHg, was, however, achieved only up to 8 hrs after drug administration, indicating that this combination given once daily is not able to normalize BP over the following 24 hrs.
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PMID:Ketanserin and hydrochlorothiazide in the treatment of arterial hypertension. 192 Aug 17

In this report the Authors have verified the effects of Ketanserin on glycaemic metabolism of type II diabetic subjects with a moderately high blood pressure. They think that a therapeutic dose of drug is not able to considerably inhibit insulin production. The Authors can assert that the Ketanserin does not influence the glycaemic regulation by therapeutic dose, neither does it increase the diabetic disease, nor disturb the oral hypoglycaemic therapy though it normalizes high blood pressure.
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PMID:[Effects of ketanserin on glucose metabolism in hypertensive diabetic subjects]. 196 64

Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S2-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was greater than or equal to 95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p less than 0.05) and concentration (p less than 0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p less than 0.05). Ketanserin treatment reduced the incidence of nightmares (p less than 0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin antagonism reduces the adverse symptoms of beta blockade. 198 Oct 22

Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Plasma concentrations of ketanserin (and some metabolites) can be measured with high performance liquid chromatography using ultraviolet or fluorescence detection, or by radioimmunoassay. The methods are sensitive, accurate and specific. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. It is subject to considerable extraction and metabolism in the liver (first-pass effect) and the absolute bioavailability is around 50%. The compound is extensively distributed to tissues and the volume of distribution is in the order of 3 to 6 L/kg. In plasma ketanserin binds avidly to plasma proteins, mainly albumin, and the free fraction is around 5%. Ketanserin is extensively metabolised and less than 2% is excreted as the parent compound. The major metabolic pathway is by ketone reduction leading to formation of ketanserin-ol which is mainly excreted in the urine. Ketanserin-ol, which by itself does not contribute to the overall pharmacological effect, is partly reoxidised into ketanserin, and it is likely that the terminal half-life of the parent compound is related to the slow ketanserin regeneration from the metabolite. Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3 h. The terminal half-life is similar after oral administration. Following long term oral dosing (20 or 40 mg twice daily) the pharmacokinetics remain linear and steady-state concentrations, which can be predicted from single-dose kinetics, are reached within 4 days. During long term treatment with the common dosage of 40 mg twice daily, steady-state concentrations fluctuate between 40 micrograms/L (trough) and 100 to 140 micrograms/L (peak). The pharmacokinetic properties of ketanserin are predictable in a wide group of patients and there is no influence from the duration of treatment, age and sex of the patient or concomitant treatment with beta-blockers or diuretics. There is no direct relationship between plasma concentrations of ketanserin and the antihypertensive effect in a group of patients. Side effects, including prolongation of the Q-T interval, are dose-dependent and, at least in the individual patient, related to peak plasma concentrations. In separate studies the pharmacokinetics of ketanserin were investigated in special patient groups, namely the elderly and patients with hepatic and renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of ketanserin. 203 47

Ketanserin is a 5-HT2 receptor antagonist without partial agonist properties which also possesses weak alpha 1-adrenoceptor antagonistic activity, which may explain its antihypertensive mechanism of action in patients with essential hypertension. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. The antihypertensive effect of oral ketanserin 40 mg twice daily is comparable with that of total daily doses of metoprolol 200 mg, propranolol 160 mg, captopril 100 mg, enalapril 20 mg, hydrochlorothiazide 50 mg, or alpha-methyldopa 1000 mg and is achieved without adverse effect on plasma lipoproteins or carbohydrate metabolism in patients with concomitant diabetes mellitus. Evidence from prospective studies suggests a greater antihypertensive efficacy in the elderly than in younger patients. In patients with intermittent claudication, results have been inconsistent in small studies, while a large study showed no improvement in pain-free walking distance but fewer amputations compared to placebo. In Raynaud's phenomenon symptomatic improvement relative to placebo was achieved in larger trials. Its role in preventing atherosclerotic complications requires further investigation. Ketanserin is reasonably well tolerated, the frequency of adverse effects being comparable with that of other antihypertensive drugs in controlled trials. Dizziness, tiredness, oedema, dry mouth and weight gain are the most commonly reported effects. Ketanserin prolongs QT interval in a dose-related manner, and when given in certain predisposing circumstances ventricular arrhythmias and syncope may occur. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload. Although the arrhythmogenic potential of ketanserin in patients receiving potassium-depleting diuretics requires suitable precautions, it appears that its antihypertensive activity is suited to the elderly provided plasma potassium concentrations are normal at the start of treatment and are maintained within the normal range.
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PMID:Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. 207 1


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