The effects of ketanserin on ventricular ectopic activity in humans

Summary Ketanserin is a serotonin S₂-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42–73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, cross-over comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p<0.001) and corrected QT interval (+20 ms; p<0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p<0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients. It would seem that the implications of ketanserin treatment for cardiac rhythm depend on the electrolyte environment. The drug appears to be potentially beneficial at normal potassium concentrations, but may carry the possibility of precipitating ventricular arrhythmias in the face of hypokalemia.     

Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin

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.     

Oral dosing with ketanserin to control high blood pressure in the elderly

Summary Ketanserin is the prototype of a new class of antihypertensive drugs based on a selective blockade of serotonin S₂ receptors. A number of controlled trials have indicated that ketanserin is more effective in older than in younger subjects and that, in the elderly, ketanserin may be even more effective than other antihypertensive drugs. We set up a large multicenter trial to compare the two most common dosages of ketanserin (20 mg and 40 mg twice daily) in patients of 60 years of age and over. In these patients, blood pressures were elevated systolically (SBP160 mmHg), diastolically (DBP95 mmHg), or both, and any existing antihypertensive medication was continued at a constant dosage. The total duration of the trial was 3 months and monthly control visits were held. Throughout the Netherlands, 252 general practitioners participated in the trial, which included 462 evaluable patients. After 1 month of open treatment with 20 mg ketanserin twice daily, blood pressure was found to be fully normalized in 18% of patients, while the proportion of patients with both systolic and diastolic hypertension was reduced from 89% to 50%. In three out of four patients, an adequate and maximal fall in blood pressure was reached only after 2–3 months of treatment. In such patients, raising the ketanserin dose from 20 mg to 40 mg twice daily did not result in any faster or improved antihypertensive response. A number of symptoms related to peripheral circulatory disturbances, or possibly to hypertension itself, markedly improved during oral treatment with ketanserin.     

Platelet deactivation by 5HT2-receptor blockade parallels the antihypertensive response to ketanserin

Serotonin (5HT) has been implicated in thromboembolic complications and blood pressure elevation and both may be reduced with the 5HT2-receptor blocker ketanserin. In 17 patients with essential hypertension (WHO I and II, diastolic pressure V greater than or equal to 100 mmHg) blood pressure, platelet 5HT uptake, content and release as well as 5HT-induced shape change and aggregation were measured before and immediately after 8 weeks oral ketanserin at 20-40 mg twice daily. During ketanserin therapy, platelet 5HT release, shape change reaction and aggregation to 5HT were significantly reduced by more than 50%. These platelet effects were more pronounced in patients responsive to ketanserin (greater than or equal to 10% decrease of diastolic pretreatment pressure) and the fall in diastolic pressure correlated with the inhibition of 5HT-induced aggregation as well as the change in 5-hydroxy-indoleacetic acid (5HIAA) in platelet-rich plasma (PRP; P less than 0.05). Serotonin-receptor-independent platelet events were not affected by ketanserin. Ketanserin corrects 5HT2-receptor-mediated platelet function along with the reduction of blood pressure.     

Ketanserin and captopril interaction in the treatment of essential hypertensives

Summary The aim of the study was to evaluate whether the combination of ketanserin with captopril exerts an additive antihypertensive effect, as compared with single drug treatment. Twelve patients with uncomplicated moderate essential hypertension received, according to a randomized, double-blind, crossover design, ketanserin (40 mg twice daily), captopril (50 mg twice daily), the combination of the two drugs at these dosages, and the corresponding placebo, each treatment being given for 1 month. Both ketanserin and captopril as monotherapy similarly and significantly reduced blood pressure as compared with placebo (p<0.001). The combination treatment of ketanserin plus captopril further and significantly reduced blood pressure when compared with single drug treatment (p<0.001). Moreover, the percentage of responders and patients whose blood pressure was normalized were significantly greater under the combined treatment than under ketanserin or captopril monotherpy (p<0.001). These data indicate that the combination of ketanserin plus captopril exerts a clear additive antihypertensive effect when compared with each treatment as monotherapy, a finding that suggests this combination can be usefully employed in the treatment of hpertensive patients.     

Hemodynamic and neurohumoral effects of ketanserin, a 5-HT2 receptor antagonist in patients with congestive heart failure

Ketanserin, a recently developed 5-HT2 receptor antagonist, competitively and selectively blocks the vasoconstrictor activity of 5-hydroxytryptamine (serotonin). We explored a possible contribution of serotonin to augmented vascular tone in patients with severe heart failure, using intravenous and oral formulations of ketanserin. When administered intravenously (10 mg bolus, 4 mg/hr infusion for +/- 40 min) to 10 patients with congestive heart failure (NYHA III or IV) secondary to congestive cardiomyopathy (n = 8) or ischemic heart disease (n = 2), the drug produced a significant increase in cardiac output (rest 24%, p less than 0.001; exercise 19%, p less than 0.01) which was accompanied by a fall in systemic arterial pressure (rest 7%, p less than 0.001; exercise 10%, p less than 0.05) and pulmonary wedge (rest 17%, p less than 0.05; exercise 23%, p less than 0.001) pressure. Calculated systemic vascular resistance (SVR, rest 27%, p less than 0.001; exercise 23%, p less than 0.05) decreased significantly. No significant hemodynamic changes were observed when 40 mg of ketanserin was administered orally to the same group of patients. Plasma catecholamines (norepinephrine, NEP:epinephrine, EP:dopamine) were measured before and after ketanserin at rest and during exercise. Baseline NEP levels were markedly elevated at rest and during exercise in all patients (rest: 878 +/- 381 ng/mL, exercise: 1453 +/- 697 ng/mL). Baseline EP levels were within normal limits. Ketanserin did not produce any change in catecholamine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin

Efficacy and safety of ketanserin were studied prospectively in a randomized, double-blind trial involving 221 patients treated for hypertension or coronary artery disease, or both. Since ketanserin has been suggested to cause QTc prolongation, the incidence and severity of this effect were investigated, as was the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in period, all patients were examined: blood pressure was measured and electrocardiograms and 24-hour Holter electrocardiograms were obtained. Two thirds of the patients (n = 147) were then randomized to receive ketanserin for 1 week (20 mg twice daily) followed by 3 weeks of 40 mg twice daily; one third of the patients (n = 74) received placebo (twice daily) for 4 weeks. After 4 weeks of treatment, blood pressure, electrocardiograms and 24-hour Holter electrocardiograms were repeated. In hypertensive patients, ketanserin significantly reduced systolic (mean reduction 17 +/- 2 mm Hg, p less than 0.0001) and diastolic blood pressure (12 +/- 1 mm Hg, p less than 0.0001) compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean 400 to 418 ms, p less than 0.01) but not with placebo (399 vs 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of nitrendipine and verapamil on plasma levels,urinary excretion,and beta-blocking effect of metoprolol

Summary Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its -hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.     

Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension

The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.     

A double-blind study of the blood pressure lowering effect of a thiazide diuretic in hypertensive patients already on nifedipine and a beta-blocker

Twelve hypertensive patients who were already on treatment with atenolol (100 mg once daily) and nifedipine as tablets (20 mg twice daily) were entered into a double-blind, randomized crossover study of the addition of 1 month's treatment with either bendrofluazide (5 mg once daily) or a matching placebo. The addition of bendrofluazide to the combination of atenolol and nifedipine did not cause any statistically significant fall in the blood pressure 2 h after the last dose of nifedipine compared to treatment with placebo [bendrofluazide: 135.2 +/- 5.1/89.8 +/- 2.5 (mean +/- s.e.), versus placebo: 132.1 +/- 4.6/89.9 +/- 3.1 mmHg; P = NS]. However, 12 hours after the last dose of nifedipine blood pressure tended to be lower whilst on bendrofluazide compared with placebo. Plasma urate levels were significantly higher on the diuretic compared to placebo (461 +/- 27 versus 396 +/- 21 mumol P less than 0.001). Plasma potassium was lower on the diuretic compared to placebo (3.59 +/- 0.12 vs 3.76 +/- 0.10) but this difference just failed to reach statistical significance. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on treatment with atenolol and nifedipine, particularly when nifedipine is maximally effective. However, the addition of a diuretic does have potentially deleterious metabolic effects.     

Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.     

Influence of long-term treatment with ketanserin on blood pressure,pulmonary artery pressure,and cardiac output in patients with heart failure

Summary Ketanserin is a selective serotonin₂-receptor blocker and by this mechanism decreases peripheral resistance and blood pressure in hyertensives. We examined the hemodynamic effects of ketanserin during long-term treatment in patients with heart failure. Five male patients with coronary artery disease and heart failure (NYHA classes II–III) were treated with ketanserin (80 mg daily) for 12 months. Before treatment, after 4 weeks, and after 12 months treatment, a Swan-Ganz catheter was placed into the pulmonary artery and pulmonary wedge pressure, cardiac output, mean arterial pressure, and heart rate were measured at rest and on exertion. The pulmonary wedge pressure at rest decreased from 8 mmHg before to 6 mmHg after 4 weeks and 12 months treatment; on exertion, it decreased from 31 mmHg before treatment to 24 mmHg after 4 weeks treatment and to 21 mmHg after 12 months treatment. The mean arterial pressure also decreased at rest and on exertion after 4 weeks treatment as well as after 12 months treatment. Cardiac output increased slightly and heart rate was unaltered. No serious side effects occurred. Ketanserin could become an alternative vasodilator drug in the treatment of patients with heart failure.     

The antihypertensive efficacy of ketanserin in the elderly evaluated by ambulatory blood pressure measurement

To assess the role of the serotonin antagonist ketanserin in the management of hypertension in the elderly, 12 patients with a mean age of 68 years (range 60-79 years) were treated with ketanserin in a randomised double-blind placebo-controlled cross-over trial. Clinic BP, ambulatory BP, renal function, and pharmacokinetics were assessed. The doses of ketanserin used were 40 mg (ten patients) and 20 mg (two patients) twice daily for 8 weeks. Mean clinic sitting BP was reduced from 169 +/- 5/98 +/- 2 on placebo to 155 +/- 5/88 +/- 3 mmHg (NS/P less than 0.05/P less than 0.05) and standing pressure from 168 +/- 6/100 +/- 3 to 157 +/- 5/91 +/- 3 mmHg (NS/P less than 0.01). Mean ambulatory systolic BP was unaffected by active treatment (167 +/- 7 vs 164 +/- 5) while diastolic pressure was lowered from 99 +/- 2 to 94 +/- 2 mmHg (P less than 0.05). This effect appeared to be mainly confined to the first two hours after drug administration. Renal blood flow was unaltered by treatment. The mean plasma half-life of ketanserin was 20.9 +/- 5.5 hours. Side effects were minimal. In conclusion, while ketanserin may be effective as assessed in the clinic, its efficacy on ambulatory monitoring is substantially less impressive.     

Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide.

OBJECTIVES: To compare quality of life with the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide in patients with mild to moderate hypertension. DESIGN AND SETTING: Multi centric, randomised, double-blind, two-way crossover study carried out at six general practice centres. SUBJECTS: Eighty-one patients with newly diagnosed or previously treated hypertension, who had a mean diastolic blood pressure (BP) of 95-120 mm Hg after receiving placebo for 4-6 weeks.Interventions: In random order, patients received bisoprolol (5 mg once daily) or bendrofluazide (2. 5 mg once daily) for 8 weeks. MAIN OUTCOME MEASURES: Quality of life and antihypertensive effect.Results: Decrease in systolic/diastolic BP did not differ between bisoprolol (10 +/- 2/13 +/- 1 mm Hg) and bendrofluazide (9 +/- 2/11 +/- 1 mm Hg). Between bisoprolol and bendrofluazide neither in the intention-to-treat nor in the efficacy analysis any difference was found in quality of life variables, such as Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms and hostility score. Compared to baseline the Health Status Index improved (P < 0.05) during bisoprolol. None of the other investigated quality of life variables changed compared to baseline. No patients dropped out during bisoprolol or bendrofluazide treatment. Although, the total number of reported adverse events appeared lower during bendrofluazide than during bisoprolol treatment, it is unclear whether drug related adverse events also differ between the two drugs. CONCLUSIONS: At equipotent antihypertensive dosages, the effect of an 8-week treatment on quality of life does not differ between the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide.     

Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies

If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.     

Ketanserin in the Treatment of Hypertension: A Multicentre Dose-Finding Study in China

The effect of ketanserin at 5 mg, 10 mg and 20 mg twice daily for 3 months was studied in Chinese patients with hypertension. Both 10 mg and 20 mg doses twice daily effectively reduced systolic and diastolic pressures, while 5 mg twice daily was not effective. The 20 mg regimen was more effective than 10 mg in reducing diastolic, but not systolic pressures. Blood pressure reduction was progressive up to 1 month of treatment but not thereafter. Neither first-dose hypotension nor postural hypotension were seen. There were no effects on body weight or heart rate. A nominally significant 6 msec increase in QTc was seen with 10 mg, but not with 5 or 20 mg twice daily; this could be a chance finding. The side-effect burden was light, and decreased with time.     

Effects of ketanserin on intraocular pressure

Summary There is evidence that some antihypertensive drugs, such as beta blockers, are effective in reducing intraocular pressure (IOP) and are commonly used in the medical treatment of glaucoma. The aim of this study was to evaluate the effects of the anti-serotonergic agent ketanserin, which has associated alpha₁-blocking properties, on IOP in normotensive and hypertensive eyes. The first part of the study was performed in six arterial hypertensive patients (mean ± SD blood pressure 156/102 ± 10/6 mmHg) with a pretreatment IOP in the normal range (15.7 ±1mmHg). Both blood pressure and IOP were measured at baseline and at 1 hour intervals up to 3 hours following the oral administration of ketanserin 20 mg or placebo, given in a randomized manner. Three hours after ketanserin treatment, mean systolic and diastolic blood pressures dropped by 10/5 mmHg and mean IOP was reduced by 2.7 mmHg; after placebo, no change was observed in these variables. Thereafter, four normotensive patients with chronic open-angle glaucoma (IOP=22.8 mmHg) were given 20 mg ketanserin orally. Three hours after administration, a 22% reduction in mean IOP occurred (-5.8 mmHg), with a concomitant reduction in mean systolic blood pressure of 13.0 mmHg. These results indicate that ketanserin treatment reduces IOP and systemic blood pressure. Further, long-term studies are needed in order to confirm the efficacy of ketanserin in the medical treatment of ocular hypertension.     

Experience With Ketanserin,A Serotonin (S2) Antagonist,in Longterm Treatment of Essential Hypertension

Ketanserin is a quinazoline derivative which acts selectively on serotonin (S₂) receptors. The compound has been shown to possess antihypertensive properties. BP and HR were measured blindly on 14 patients with essential hypertension during one year. Ketanserin 40 mg, once or twice daily, reduced BP (and HR to a slight extent) largely unchanged from 14 days after initiation of therapy. Response rate varied from 57–77% at the regular control visits. During the one year follow up period the reduction in supine SBP was 9±3% (p < 0.001) and DBP was 12±1% (p < 0.001) The only side effect was a slight sedation that passed with time.

It is concluded that ketanserin is effective in the chronic treatment of hypertension and may offer a new alternative to existing pharmacotherapy.     

Antihypertensive and metabolic effects of ketanserin in diabetic patients with mild hypertension

Ketanserin is a serotonin S2 receptor antagonist with antihypertensive activity. Its effects on blood pressure, glucose metabolism and serum lipids were assessed in 24 patients with diabetes mellitus and mild arterial hypertension in a double blind, placebo-controlled trial. Ketanserin in doses up to 80 mg daily caused a slight decrease of supine BP (from 159/97 +/- 19/11 to 153/90 +/- 20/9 mm Hg; NS/P less than 0.01) and upright BP (from 160/102 +/- 18/13 to 151/93 +/- 12/12 mm Hg; P less than 0.05/NS). However, these pressures did not differ significantly from the levels observed in the placebo group. Supine and upright heart rate, body weight, plasma sodium and potassium, serum creatinine, glucose, C-peptide, glycosylated haemoglobin, serum cholesterol and triglycerides, their lipoprotein fractions, apolipoprotein A1, A2 and B concentrations and the responses of serum glucose and insulin to a standard oral glucose loading test did not change. These findings indicate that the selective S2 receptor antagonist ketanserin did not unfavourably influence glucose and lipid metabolism in diabetic patients with arterial hypertension.     

Treating hypertension in non-insulin-dependent diabetes: a comparison of atenolol, nifedipine, and captopril combined with bendrofluazide

Twenty-five of thirty NIDDS who remained hypertensive (diastolic greater than 95 mmHg supine) after 4 weeks on bendrofluazide 2.5 mg daily (B), completed a single-blind, observer-blind randomized crossover study, in which the additional use of atenolol (50 mg daily) (A), slow-release nifedipine (20 mg twice daily) (N), and captopril (25 mg twice daily) (C) was compared. Patients took each drug for 8 weeks with dose doubling at 4 weeks if supine diastolic remained greater than 90 mmHg. All three combinations were more effective than bendrofluazide alone (p less than 0.01). In nine patients studied 2 h after tablets at the end of each treatment period nifedipine was more effective than the other two drugs (B:174/104 mmHg, A:162/95 mmHg, -8%, N:141/88 mmHg, -17%, C:157/94 mmHg, -10%, supine), whereas in 16 patients studied 15 h after their evening dose there was no significant difference. Fasting insulin and HbA1 levels were not significantly different between groups. No drug had a significant adverse effect on creatinine, glomerular filtration rate, overnight urinary albumin excretion or foot transcutaneous oxygen levels (43 degrees C). All three drugs studied were effective without deleterious effects on renal function or peripheral blood flow.