Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. 207 1

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.
 ...
PMID:Antihypertensive efficacy of ketanserin alone or in combination with a beta-blocker or a diuretic: the Swiss Ketanserin Study. 244 58

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.
 ...
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.
 ...
PMID:Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin. 280 91

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.
 ...
PMID:Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. 327 10