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1.
Eur J Obstet Gynecol Reprod Biol ; 189: 106-11, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25892082

RESUMO

OBJECTIVE: Determine the definitive position of ketanserin and dihydralazine for treatment of severe hypertension in pregnancy. STUDY DESIGN: A single centre double blind randomized controlled trial was performed at the obstetrical tertiary high care unit of the University Medical Centre in Rotterdam, the Netherlands. Women with severe hypertension in pregnancy (diastolic blood pressure (DBP)≥110mmHg), and significant proteinuria (≥300mg/24h), and gestational age≤32 weeks were eligible for the study. All patients (n=30) received two infusions (double dummy technique): one contained the active ingredient (ketanserin or dihydralazine), the other was used for placebo. Nicardipine was used as rescue medication. The main outcome measures were persistent severe hypertension (DBP>100mmHg>120min) despite maximum dosage of study medication and prolongation of pregnancy. RESULTS: Dihydralazine was significantly more effective in lowering blood pressure than ketanserin. No significant difference in prolongation of pregnancy was seen between the two groups. After 30 inclusions, the study was stopped because of the high rate of persistent hypertension using ketanserin and the high rate of maternal side effects using dihydralazine and the apparent succesful use of the rescue drug nicardipine. CONCLUSIONS: Our results do not support the use of either dihydralazine or ketanserin for the treatment of severe hypertension in pregnancy. Future research is needed to compare nicardipine with other antihypertensive drugs currently in use for treatment of severe hypertension in pregnancy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidralazina/uso terapêutico , Hipertensão/tratamento farmacológico , Ketanserina/uso terapêutico , Pré-Eclâmpsia/fisiopatologia , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Adulto , Di-Hidralazina/efeitos adversos , Método Duplo-Cego , Feminino , Idade Gestacional , Hospitais Universitários , Humanos , Hipertensão/complicações , Ketanserina/efeitos adversos , Países Baixos , Nicardipino/uso terapêutico , Gravidez
3.
Arq. bras. med. vet. zootec ; 61(1): 144-148, fev. 2009. ilus, tab
Artigo em Português | LILACS | ID: lil-513035

RESUMO

Estudou-se a eficácia do uso tópico de ketanserina como promotor da cicatrização de feridas cutâneas induzidas em equinos. As feridas foram produzidas em ambos os metâmeros na região da garupa de oito cavalos adultos, em formato quadrangular, medindo cinco centímetros de lado. Aleatoriamente um dos metâmeros foi escolhido como tratado, permanecendo o contralateral como controle. As lesões do grupocontrole foram lavadas somente com água e detergente neutro e no grupo tratado foi realizado o mesmo procedimento seguido de aplicação tópica de ketanserina. A evolução macroscópica e microscópica do processo cicatricial foi avaliada e a área de cada ferida determinada no decorrer do período experimental. Não foram verificadas diferenças significativas entre as feridas do grupo-controle e do grupo tratado com ketanserina durante 56 dias de avaliação.


The efficiency of topical use of kentaserin on healing evolution of induced skin wounds in horses was studied. The experimental surgical wounds were made in both sides of the croup of eight adult horses. The wounds were square-shaped measuring 5cm of each side. One side was considered control and the opposite one treated. Both control and treated animals were rinsed with water and neutral soap. Additionally, the wound on the treated horses received the topical treatment with ketanserin. Macroscopic and microscopic healing evolution of the wounds was evaluated and their areas were determined during the experimental period. The use of topical ketanserin showed no difference between the control and the treated wounds during a period of 56 days.


Assuntos
Animais , Cicatrização , Equidae , Ketanserina/administração & dosagem , Ketanserina/efeitos adversos , Pele
4.
Br J Pharmacol ; 155(3): 365-73, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18574455

RESUMO

BACKGROUND AND PURPOSE: Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiac ether-à-go-go-related gene (hERG) potassium channels. EXPERIMENTAL APPROACH: Whole-cell patch voltage-clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes. KEY RESULTS: Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 microM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 microM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 microM (7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2-59 fold) by ketanserin. CONCLUSIONS AND IMPLICATIONS: These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.


Assuntos
Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Ketanserina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Antagonistas da Serotonina/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Eletrocardiografia , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Concentração Inibidora 50 , Ketanserina/administração & dosagem , Ketanserina/efeitos adversos , Técnicas de Patch-Clamp , Potássio/metabolismo , Bloqueadores dos Canais de Potássio/administração & dosagem , Bloqueadores dos Canais de Potássio/efeitos adversos , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/efeitos adversos
5.
Eur J Obstet Gynecol Reprod Biol ; 95(1): 22-36, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11267716

RESUMO

Hypertensive disorders of pregnancy are the leading cause of maternal and perinatal mortality and morbidity in developing and developed countries. The etiology of preeclampsia is still unknown. Delivering the baby is the only definite treatment. The benefits of acute pharmacological control of severe hypertension prior to and/or post-delivery are generally accepted. Most drugs commonly used in the management of severe hypertension in pregnancy have significant maternal and/or neonatal adverse side effects. Furthermore, some are not effective to acutely lower the blood pressure in patients with a hypertensive crisis. Until recently not one of the commonly used antihypertensive drugs has been tailored to the pathophysiology of severe preeclampsia, being a clinical syndrome characterized by endothelial cell dysfunction, vasospasm and platelet aggregation. Ketanserin, a serotonin(2)-receptor blocker, is a drug that appears to be tailored for treating this pregnancy-associated enthothelial cell dysfunction. The results of several prospective trials show that there is a definite place for serotonin(2)-receptor blockers in the treatment of pregnancy-induced hypertensive disorders. This review provides a summary on the more established drugs as well as on some of the newer antihypertensive drugs used in pregnancy with emphasis on the existing experience with ketanserin.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Humanos , Ketanserina/efeitos adversos , Ketanserina/uso terapêutico , Labetalol/uso terapêutico , Metildopa/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Gravidez
6.
J Perinat Med ; 29(1): 14-22, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11234612

RESUMO

OBJECTIVE: To compare maternal and perinatal outcome with the use of either intravenous ketanserin or dihydralazine in treatment of women with preeclampsia. METHODS: The records from January 1989 to January 1997 of all patients receiving intravenous ketanserin or dihydralazine as first line antihypertensive therapy were reviewed and standardized data forms were completed. 315 charts of patients were identified and evaluated for effects on blood pressure, laboratory parameters, maternal and perinatal outcome. RESULTS: During the study interval 169 patients received ketanserin and 146 dihydralazine. Significantly fewer antepartum (27% versus 38%, p = 0.04) and postpartum (25% versus 39%, p = 0.01) maternal complications were noted in patients receiving ketanserin. Occurrence of HELLP syndrome was significantly lower among patients who received ketanserin (20%) than among those who received dihydralazine (40%, p = 0.0001). Side-effects were reported with significantly higher frequency in patients receiving dihydralazine (60%) as compared to those receiving ketanserin (17%, p < 0.0001). Perinatal outcome was comparable, however, umbilical cord arterial pH values (mean +/- SD) were higher with ketanserin compared to dihydralazine (7.25 +/- 0.07 vs 7.23 +/- 0.09, p = 0.038). The incidence of placental abruption was higher in patients receiving dihydralazine (5.5%) versus those receiving ketanserin (0.6%, p = 0.014). CONCLUSION: Ketanserin appears to be a better option than dihydralazine for treatment of severe preeclampsia since fewer maternal complications and side-effects were observed in patients receiving ketanserin.


Assuntos
Anti-Hipertensivos/uso terapêutico , Ketanserina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Aspartato Aminotransferases/sangue , Parto Obstétrico , Di-Hidralazina/efeitos adversos , Di-Hidralazina/uso terapêutico , Feminino , Idade Gestacional , Síndrome HELLP/epidemiologia , Hemólise , Humanos , Ketanserina/efeitos adversos , L-Lactato Desidrogenase/sangue , Fígado/enzimologia , Modelos Logísticos , Países Baixos/epidemiologia , Contagem de Plaquetas , Pré-Eclâmpsia/epidemiologia , Gravidez , Edema Pulmonar/epidemiologia
7.
Obstet Gynecol Surv ; 55(9): 582-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10975485

RESUMO

UNLABELLED: Most agree that antihypertensive medication should be used to treat severe hypertension during pregnancy, but its role in patients with mild to moderate disease is debated. None of the regularly used drugs is completely safe for mother and fetus. Ketanserin decreases systolic and diastolic blood pressure in nonpregnant patients with acute and chronic hypertension. Its selective serotonin S2-receptor antagonist activity encouraged investigations into a possible role in pregnant women. These reports can be divided into four groups. Several studies confirmed that intravenous ketanserin decreases blood pressure significantly in patients with severe preeclampsia. There are indications that it may be at least as effective as dihydralazine, possibly with fewer side effects. Its role in chronic hypertension has not been studied adequately, but one randomized, controlled trial indicated efficacy comparable with that of alpha-methyldopa. Thirdly, it was concluded in a single descriptive study that the administration of ketanserin to patients with HELLP syndrome allowed delivery to be postponed for 5.3 days. Lastly, in a randomized, placebo-controlled trial, the addition of ketanserin to aspirin in patients with mild to moderate midtrimester hypertension was associated with a significant decrease in the number of cases of preeclampsia and severe hypertension, as well as a trend to less perinatal mortality, lower rates of abruptio placentae, and early-onset preeclampsia. Additional studies are needed to adequately assess a possible role for ketanserin with acute hypertension or moderate chronic hypertension. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to list the various drugs and their associated side effects that are used to treat hypertensive disorders during pregnancy; to describe the various effects of serotonin on the cardiovascular system; to summarize the literature concerning the use of ketanserin during pregnancy; and to list the potential uses of ketanserin in this setting.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Ketanserina/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Antagonistas da Serotonina/uso terapêutico , Adulto , Anti-Hipertensivos/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Ketanserina/efeitos adversos , Pré-Eclâmpsia/prevenção & controle , Gravidez , Antagonistas da Serotonina/efeitos adversos
8.
Pituitary ; 3(2): 55-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11141696

RESUMO

Central serotonergic regulation could have a role in the course of pituitary-dependent Cushing's disease. We studied the effects of ritanserin and ketanserin, two related selective 5HT2 receptor antagonists, in 11 patients with Cushing's disease. Treatment lasted from 1 month to 1 year (up to 4 years in one patient). Daily doses were 10-15 mg for ritanserin, and 40-80 mg for ketanserin. Since the two drugs share the same mechanism of action and no qualitative or quantitative differences in response to their administration were observed, the results were pooled together. Patients were assessed by clinical and hormonal evaluation. Urinary cortisol and ACTH were considered the parameters of interest. Short-term response: after 1 month, there was a significant decrease of urinary cortisol from 781 (160) to 331 (215) nmol/d (P < 0.02) while ACTH was 9.8 (1.5) pmol/L baseline and again 8.8 (2.2) pmol/L at 1 month (P = NS). For 9 patients, hormonal parameters were available after 1 week of treatment. In this case, also ACTH levels were significantly decreased (from 9.6 (1.7) to 5.2 (1.3) pmol/L; P < 0.01) together with urinary cortisol (from 781 (194) to 372 (165) nmol/d; P < 0.01). Long-term response: in 3 patients, hormonal parameters failed to respond to serotonin receptor antagonists, which were thus discontinued. An improvement was recorded in the remaining 8 patients, that was prolonged in 3, and transient in 5. In 3 of these latter patients, a marked increase of ACTH was observed before treatment discontinuation. Ketanserin was given to 2 patients with Nelson's syndrome, with only transient ACTH decrease in one, and no changes in ACTH response to CRH after 1 month treatment in both cases. An inhibitory effect of ritanserin and ketanserin on ACTH and cortisol production in Cushing's disease appeared to be limited both in terms of duration of response and number of patients with a satisfactory outcome. However, the results may provide a better understanding of serotonergic modulation in Cushing's disease and lead to therapeutic developments.


Assuntos
Síndrome de Cushing/tratamento farmacológico , Ketanserina/uso terapêutico , Ritanserina/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Adolescente , Hormônio Adrenocorticotrópico/urina , Adulto , Feminino , Hormônios/sangue , Hormônios/urina , Humanos , Hidrocortisona/urina , Ketanserina/efeitos adversos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Síndrome de Nelson/tratamento farmacológico , Ritanserina/efeitos adversos , Antagonistas da Serotonina/efeitos adversos
9.
Am J Obstet Gynecol ; 180(2 Pt 1): 371-7, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9988803

RESUMO

OBJECTIVE: An open, randomized, prospective, multicenter trial was conducted to compare the efficacy and safety of intravenous ketanserin, a selective serotonin 2 receptor blocker, with that of intravenous dihydralazine in the management of severe early-onset (<32 weeks' gestation) preeclampsia. End points of this study were blood pressure control and maternal outcome. STUDY DESIGN: Patients with a diastolic blood pressure >110 mm Hg were randomly assigned to receive either ketanserin (n = 22) or dihydralazine (n = 22) as initial therapy. Plasma volume expansion preceded antihypertensive treatment, which was administered according to a fixed schedule. RESULTS: The reductions in blood pressure with the 2 drugs were similar; however, adequate blood pressure control was reached significantly earlier with ketanserin (84 +/_ 63 vs 171 +/- 142 minutes, P = .017). Occurrence of maternal complications was significantly lower among patients who received ketanserin than among patients who received dihydralazine (n = 6 vs n = 18, P =.0007). A significant difference in favor of ketanserin was noted in daily fluid balance. CONCLUSION: Antihypertensive efficacies of ketanserin and dihydralazine were comparable, but significantly fewer maternal complications were noted among the patients receiving ketanserin. Ketanserin is an attractive alternative in the management of severe early-onset preeclampsia.


Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidralazina/uso terapêutico , Ketanserina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Resultado da Gravidez , Adulto , Pressão Sanguínea , Di-Hidralazina/efeitos adversos , Feminino , Síndrome HELLP/complicações , Humanos , Ketanserina/efeitos adversos , Oligúria/complicações , Volume Plasmático , Pré-Eclâmpsia/complicações , Pré-Eclâmpsia/fisiopatologia , Gravidez , Estudos Prospectivos , Transtornos Puerperais/complicações , Equilíbrio Hidroeletrolítico
10.
J Cardiothorac Vasc Anesth ; 11(6): 729-36, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9327314

RESUMO

OBJECTIVES: To compare the hemodynamic responses, safety, and efficacy of urapidil and ketanserin in hypertensive patients after coronary artery surgery. DESIGN: Randomized double-blind study. SETTING: Multi-institutional. PARTICIPANTS: One hundred twenty-two patients undergoing elective coronary artery surgery. INTERVENTIONS: When hypertension (defined as mean arterial pressure > 85 mmHg) developed within the first 2 hours after arrival in the intensive care unit, patients received urapidil (n = 62) or ketanserin (n = 60) to reach a mean arterial pressure between 65 and 75 mmHg. Urapidil was administered by repeated bolus injections (25 to 125 mg) followed by a continuous infusion of maximally 50 micrograms/kg/min. Ketanserin was administered by repeated bolus injections (10 to 50 mg) followed by a continuous infusion of maximally 4.0 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was determined at baseline and at 30 and 60 minutes after start of study medication. In the urapidil group, mean arterial pressure (+/-SD) decreased significantly from 100.6 +/- 12.4 mmHg at baseline to 74.6 +/- 12.1 mmHg at 30 minutes and 73.5 +/- 13.8 mmHg at 60 minutes. In the ketanserin group, mean arterial pressure decreased significantly from 98.7 +/- 10.7 mmHg at baseline to 83.5 +/- 16.8 mmHg at 30 minutes and 83.1 +/- 15.3 mmHg at 60 minutes. Between the groups, there was a significant difference in the degree of lowering mean arterial pressure at 30 and 60 minutes. Heart rate increased significantly by 5.8 +/- 12.7 (30 minutes) and 8.6 +/- 16.5 (60 minutes) beats/min in the ketanserin group. In the urapidil group, no changes in heart rate occurred. Cardiac output increased to the same extent (0.7 L/min) in both groups. Within and between the groups, there were no relevant changes in pulmonary filling pressures. The number of patients not responding adequately to the study medication (mean arterial pressure > 85 mmHg after 30 minutes despite the maximum doses of study medication) was comparable in both groups (9 [U] v 13 [K]). Adverse events attributable to the study medication occurred to a similar degree in both groups. In the patients treated with urapidil, a significantly higher incidence (32.3%) of hypotension (mean arterial pressure < or = 65 mmHg for more than 10 minutes) occurred after 60 minutes of continuous infusion. CONCLUSIONS: In contrast to ketanserin, urapidil did not increase heart rate. Urapidil was more effective in lowering arterial blood pressure than ketanserin. However, one third of the patients treated with urapidil developed hypotension after 60 minutes of continuous infusion.


Assuntos
Anti-Hipertensivos/uso terapêutico , Vasos Coronários/cirurgia , Hipertensão/tratamento farmacológico , Ketanserina/uso terapêutico , Piperazinas/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Método Duplo-Cego , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Ketanserina/efeitos adversos , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Respiração/efeitos dos fármacos
11.
Eur J Obstet Gynecol Reprod Biol ; 75(2): 155-9, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9447368

RESUMO

OBJECTIVE: To compare the efficacy and safety of intravenous dihydralazine with ketanserin in the management of severe hypertension in the third trimester. STUDY DESIGN: A double blind randomised controlled trial, comparing 5 mg dihydralazine with 10 mg ketanserin after an intravenous infusion of 500 ml of a crystalloid solution. Medication was repeated every 20 min till the therapeutic goal of 90 mm Hg was reached, to a maximum of 4 dosages. Main outcome measures were treatment failures and emergency deliveries for fetal distress. RESULTS: The therapeutic goal was met more often in patients receiving dihydralazine (36/38 compared to 27/42; P < 0.01). The need for delivery for fetal distress did not differ (3 after dihydralazine, 1 after ketanserin, P = 0.29) No therapy related perinatal loss occurred, but one mother with an undiagnosed phaechromocytoma died 24 h after receiving dihydralazine. CONCLUSION: Ketanserin in this dosage is less effective to lower diastolic blood pressure. The place of a fluid load prior to dihydralazine needs to be further investigated, as fetal heart rate decelerations were less common than previously reported.


Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidralazina/uso terapêutico , Hipertensão/tratamento farmacológico , Ketanserina/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Adulto , Pressão Sanguínea , Di-Hidralazina/administração & dosagem , Di-Hidralazina/efeitos adversos , Método Duplo-Cego , Feminino , Morte Fetal/induzido quimicamente , Sofrimento Fetal/induzido quimicamente , Frequência Cardíaca Fetal , Humanos , Infusões Intravenosas , Ketanserina/administração & dosagem , Ketanserina/efeitos adversos , Gravidez
12.
Schweiz Med Wochenschr ; 122(45): 1723-7, 1992 Nov 07.
Artigo em Alemão | MEDLINE | ID: mdl-1279788

RESUMO

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.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Hipertensão/tratamento farmacológico , Ketanserina/efeitos adversos , Nifedipino/efeitos adversos , Idoso , Pressão Sanguínea/efeitos dos fármacos , Complexos Cardíacos Prematuros/induzido quimicamente , Interações Medicamentosas , Quimioterapia Combinada , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ketanserina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem
13.
Jpn Heart J ; 32(3): 307-14, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-1920817

RESUMO

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.


Assuntos
Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Ketanserina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/uso terapêutico , Hipertensão/fisiopatologia , Ketanserina/efeitos adversos , Ketanserina/uso terapêutico , Masculino , Pessoa de Meia-Idade
14.
Exp Eye Res ; 52(5): 507-10, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2065721

RESUMO

We evaluated the effect of the antihypertensive drug ketanserin, a 5-HT antagonist, on intraocular pressure (IOP) in 20 patients with ocular hypertension. IOP, pupil diameter, systolic arterial pressure (SBP), diastolic arterial pressure (DBP) and heart rate (HR) were recorded at baseline and at 1-hr intervals for 3 hr after oral administration of 20 mg ketanserin or placebo, given in a randomized, double masked, cross-over fashion. The alternative treatment was given a week later. In all patients, ketanserin significantly lowered IOP and SBP, while no variations in pupil diameter, DBP and HR were found. Moreover, after drug administration, total outflow facility, measured by conventional tonography, increased significantly. These findings indicate that oral ketanserin could represent a new antiglaucomatous drug.


Assuntos
Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Ketanserina/uso terapêutico , Administração Oral , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Ketanserina/administração & dosagem , Ketanserina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pupila/efeitos dos fármacos
16.
Clin Exp Hypertens A ; 13(4): 541-55, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1934538

RESUMO

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.


Assuntos
Hipertensão/tratamento farmacológico , Ketanserina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ketanserina/efeitos adversos , Ketanserina/uso terapêutico , Masculino
17.
Life Sci ; 48(19): 1809-12, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-2041454

RESUMO

Ketanserin, as a 5HT2 selective antagonist, was evaluated for its tocolytic effects in pregnant Charles River (CR) rats, at total doses of 1.5 and 3.5 mg/kg IU from day 22 to day 25 of pregnancy. After 18 hours of ethenyl estradiol induction, tocolytic evaluation was carried out by recording uterine activity. When compared to the control group, the administration of Ketanserin resulted in an apparent, nondose dependent suppression of uterine contractility.


Assuntos
Ketanserina/farmacologia , Prenhez/efeitos dos fármacos , Tocolíticos/farmacologia , Animais , Bradicardia/induzido quimicamente , Feminino , Ketanserina/efeitos adversos , Gravidez , Ratos , Antagonistas da Serotonina/farmacologia
18.
Ann Ital Med Int ; 5(4 Pt 2): 469-76, 1990.
Artigo em Italiano | MEDLINE | ID: mdl-2102134

RESUMO

The antihypertensive efficacy of a receptor antagonist of serotonin was compared with a widely known antihypertensive drug, metoprolol, and their effects on cardiac and forearm hemodynamics were studied using echocardiography and flowmetry with pulsed bidimensional Doppler. Twenty patients with hypertension completed a randomized double-blind crossover study, using ketanserin and metoprolol. Two periods of 5 weeks with ketanserin or metoprolol were preceded by a placebo period the total duration of the study was 15 weeks. Although comparable efficacy in reducing systolic and diastolic pressure, (by about 10% of base-values), was observed, the two drugs showed quite different effects on forearm hemodynamics. Ketanserin increased blood flow to the forearm and induced a significant decrease in the vascular resistances of the forearm (from 141 +/- 16 to 75 +/- 11 mmHg/mL/s; p less than 0.01). Moreover, this treatment was able to improve the compliance of the brachial artery (from 1.89 +/- 0.3 to 3.2 +/- 0.3 cm4/dyn 10(-10); p less than 0.01). On the contrary, metoprolol did not modify forearm hemodynamics. Neither drug modified cardiac performance, as assessed by the circumferential shortening of the fibers of the left ventricle. Cardiac output was increased by ketanserin (from 5.9 +/- 0.3 to 6.6 +/- 0.5 L/min; p less than 0.05) and reduced during treatment with metoprolol (from 5.9 +/- 0.4 to 4.9 +/- 0.3 L/min; p less than 0.01). Thus the two drugs reduced arterial pressure by different hemodynamic mechanisms and the effects of ketanserin on systemic and peripheral circulation seem more favourable.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/efeitos dos fármacos , Antebraço/irrigação sanguínea , Hipertensão/tratamento farmacológico , Ketanserina/farmacologia , Metoprolol/farmacologia , Adulto , Complacência (Medida de Distensibilidade) , Método Duplo-Cego , Ecocardiografia , Feminino , Frequência Cardíaca , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Ketanserina/efeitos adversos , Ketanserina/uso terapêutico , Masculino , Metoprolol/efeitos adversos , Metoprolol/uso terapêutico , Ultrassom
19.
Ann Ital Med Int ; 5(4 Pt 2): 433-50, 1990.
Artigo em Italiano | MEDLINE | ID: mdl-2102130

RESUMO

Ketanserin is a specific antagonist of the 5-HT2 serotoninergic receptors; it is located on the smooth muscle cells of the vessel wall, and its stimulation causes vasoconstriction. The aim of this study is to evaluate the antihypertensive effect of ketanserin in patients with essential and secondary hypertension. Both systolic and diastolic blood pressure significantly decreased, in 18 patients, after chronic treatment with oral therapy (40-80 mg/day), and in 37 patients, after acute administration of sublingual (20 mg) and intravenous (10 mg) ketanserin. Acute administration of ketanserin was less effective than nifedipine (10 mg) in severe hypertension. Ketanserin, compared to placebo, permitted the normalization of blood pressure in 6/10 patients. Cardiovascular effects of ketanserin were studied with the ECOCG method in 8 patients with hypertension: peripheral resistances decreased, but left ventricular function and structure did not change. The effect of ketanserin on Na transmembrane transport systems in erythrocytes was studied both in vivo and in vitro, in order to evaluate the ketanserin action mechanism. The Na/K pump decreased and Na/Li countertransport increased, while different concentrations of serotonin did not change the transmembrane transport systems. In conclusion, ketanserin has a direct effect on transmembrane transport systems, not mediated by the serotonin receptors. This effect, with an antagonist of 5-HT2 serotoninergic and alpha 1 adrenergic receptor action, can cause a hypotensive effect.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Ketanserina/farmacologia , Adulto , Idoso , Fenômenos Bioquímicos , Bioquímica , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/sangue , Ketanserina/efeitos adversos , Ketanserina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nifedipino/farmacologia , Nifedipino/uso terapêutico , Potássio/sangue , Renina/sangue , Sódio/sangue
20.
G Ital Cardiol ; 20(9): 869-72, 1990 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-2079190

RESUMO

The authors report the case of an 84-year-old man with mild aortic valvular disease and arterial hypertension who developed marked QT interval prolongation and several lipotimic and syncopal attacks after 3 months of treatment with ketanserin (40 mg/day). The correlation between ketanserin, QT prolongation and symptoms was assessed by withdrawal and subsequent re-administration of the drug. Continuous ECG monitoring revealed the occurrence of QT prolongation and symptomatic runs of torsade de pointes ventricular tachycardia. The Authors suggest that treatment with ketanserin needs careful patients selection and follow-up.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Ketanserina/efeitos adversos , Torsades de Pointes/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/tratamento farmacológico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Síncope/induzido quimicamente , Síncope/fisiopatologia , Torsades de Pointes/fisiopatologia
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