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1.
Int J Clin Pharmacol Ther ; 37(7): 323-31, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10442506

ABSTRACT

OBJECTIVE: The aim of this study was to compare the effect of amlodipine and enalapril on platelet aggregation, and platelet production of malondialdehyde in patients with mild to moderate arterial hypertension. PATIENTS AND METHODS: A parallel, double-blind, placebo-controlled study was carried out in 24 patients (2 groups of 12 patients each). Initially all patients received placebo for four weeks; then amlodipine, 5 mg daily or enalapril 20 mg daily taken once a day at 7 am. Dosage was doubled after 4 weeks when diastolic blood pressure was > 90 mmHg in sitting position, the treatment was continued for 12 weeks. At the end of placebo and active phases a platelet aggregation test, using adenosine diphosphate, collagen and adrenaline, and a platelet malondialdehyde production test, either in basal conditions (MDA-basal) and after the stimulation of arachidonic acid pathway by adding ethylmaleimide (MDA-activated) were carried out. RESULTS: Blood pressure was reduced by both agents, enalapril and amlodipine. Enalapril controlled 58.3% of hypertensive patients with an average dosage of 31.7 mg/daily. Amlodipine controlled 75% of patients with a dosage of 7.1 mg/daily. Platelet aggregation was reduced by amlodipine in 15.9% for ADP (10 microM); 17.4% for collagen (2 microg/ml) and 19.9% for adrenaline (2 microM) (p < 0.025). Meanwhile enalapril slightly increased platelet aggregation by 6.7%, 1.3% and 5.6% for the three agents, respectively (p > 0.05, ns). Malondialdehyde was reduced by amlodipine in 45.33% (p < 0.05) for MDA-basal; 3.76% (p > 0.05) for MDA-activated; and the ratio MDA-basal:MDA-activated in 36.79% (p < 0.005). Meanwhile enalapril increased MDA-basal in 2.89%; MDA-activated in 3.58% and reduced the ratio MDA-basal:MDA-activated, in 10.34% (p > 0.05). CONCLUSION: Both agents, enalapril and amlodipine, reduced blood pressure, but only amlodipine reduced platelet aggregation and platelet production of malondialdehyde, indicating its action on the arachidonic acid metabolic pathway.


Subject(s)
Amlodipine/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Enalapril/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation/drug effects , Amlodipine/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Calcium Channel Blockers/pharmacology , Double-Blind Method , Enalapril/pharmacology , Female , Humans , Hypertension/drug therapy , Male , Malondialdehyde/metabolism , Middle Aged , Platelet Aggregation Inhibitors/pharmacology , Platelet Function Tests
2.
Invest Clin ; 38 Suppl 2: 41-6, 1997 Nov.
Article in Spanish | MEDLINE | ID: mdl-9471230

ABSTRACT

Hypertension is a major risk factor for stroke/myocardial infarction as expression of the atherogenic process. Platelets play a fundamental role in all these disease processes. In physiological conditions there is an equilibrium between pro aggregating and anti aggregating factors. In pathological situations this equilibrium is broken and pro aggregating factors are predominant . Patients with hypertension have an state of hyper-aggregation and dysequilibrium in the production of eicosanoids. Some antihypertensive drugs tend to not only reduce blood pressure to control levels but to reduce platelet aggregation and re-establish the broken equilibrium in eicosanoid production.


Subject(s)
Hypertension/blood , Platelet Aggregation , Adult , Aged , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Apyrase/metabolism , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/etiology , Eicosanoids/metabolism , Endothelium, Vascular/embryology , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Nitric Oxide/metabolism , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Risk Factors , Vasodilation/physiology , Venezuela/epidemiology
3.
Rev. argent. cardiol ; 64(supl. 4): 65-73, 1996. ilus, tab, graf
Article in Spanish | BINACIS | ID: bin-20924

ABSTRACT

El cumplimiento en el tratamiento antihipertensivo es muy importante para proteger al paciente de las complicaciones cardíacas y cerebrovasculares de la hipertensión. Con el régimen de dos veces al día, el 50 por ciento toman la medicación prescripta el 90 por ciento de los días de observación, comparado con el 70 por ciento cuando los pacientes cumplen la medicación una vez al día. la acción antihipertensiva de la amlodipina y el enalapril ha sido publicada recientemente por nuestro grupo de investigación, en un estudio controlado, paralelo, doble ciego y al azar. Después de cuatro semanas de recibir placebo en forma ciego-simple, los pacientes fueron asignados a recibir 20 mg de enalapril (15 pacientes) o 5 mg de amlodipina (15 pacientes) una vez al día. En la cuarta semana de medicación activa la dosis fue duplicada, en caso que la presión arterial diastólica en posición sentada fuera superior a 90 mmHg. Un monitoreo ambulatorio de presión arterial fue realizado al final de la etapa placebo por un período de 24 horas y al final de la semana 12 de tratamiento activo por un período de 48 horas. Las reducciones en la presión arterial fueron mayores en el grupo amlodipina (AU)


Subject(s)
Humans , Hypertension/drug therapy , Hypertension/therapy , Hypertension/complications , Amlodipine/administration & dosage , Amlodipine/pharmacology , Amlodipine/therapeutic use , Enalapril/administration & dosage , Enalapril/pharmacology , Enalapril/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Blood Pressure Monitoring, Ambulatory , Venezuela
4.
Rev. argent. cardiol ; 64(supl. 4): 65-73, 1996. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-194142

ABSTRACT

El cumplimiento en el tratamiento antihipertensivo es muy importante para proteger al paciente de las complicaciones cardíacas y cerebrovasculares de la hipertensión. Con el régimen de dos veces al día, el 50 por ciento toman la medicación prescripta el 90 por ciento de los días de observación, comparado con el 70 por ciento cuando los pacientes cumplen la medicación una vez al día. la acción antihipertensiva de la amlodipina y el enalapril ha sido publicada recientemente por nuestro grupo de investigación, en un estudio controlado, paralelo, doble ciego y al azar. Después de cuatro semanas de recibir placebo en forma ciego-simple, los pacientes fueron asignados a recibir 20 mg de enalapril (15 pacientes) o 5 mg de amlodipina (15 pacientes) una vez al día. En la cuarta semana de medicación activa la dosis fue duplicada, en caso que la presión arterial diastólica en posición sentada fuera superior a 90 mmHg. Un monitoreo ambulatorio de presión arterial fue realizado al final de la etapa placebo por un período de 24 horas y al final de la semana 12 de tratamiento activo por un período de 48 horas. Las reducciones en la presión arterial fueron mayores en el grupo amlodipina


Subject(s)
Humans , Amlodipine/administration & dosage , Amlodipine/pharmacology , Amlodipine/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Enalapril/administration & dosage , Enalapril/pharmacology , Enalapril/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Hypertension/therapy , Blood Pressure Monitoring, Ambulatory , Venezuela
5.
Clin Ther ; 15(2): 304-13, 1993.
Article in English | MEDLINE | ID: mdl-8519039

ABSTRACT

Ten patients (mean age, 46 years) with mild to moderate hypertension received 5 mg of amlodipine daily for 12 weeks. The amlodipine dose was increased to 10 mg daily in 4 patients whose blood pressure remained > or = 90 mmHg during the first 8 weeks. After 8 and 12 weeks of treatment, mean blood pressures in the supine, sitting, and standing positions and after exercise were reduced significantly. Heart rate did not change significantly from before to after treatment. Six hours after amlodipine administration, however, slight but significant increases in heart rate were noted at rest and after exercise. Platelet aggregation induced by adenosine diphosphate or collagen was significantly reduced 6 hours after amlodipine. One patient reported headache after the 10-mg dose of amlodipine. No other side effects were noted. It is concluded that 10 mg of amlodipine once daily is safe and effective in the treatment of mild to moderate hypertension.


Subject(s)
Amlodipine/pharmacology , Blood Pressure/drug effects , Hypertension/physiopathology , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Adult , Aged , Amlodipine/therapeutic use , Exercise , Female , Heart Rate/drug effects , Humans , Hypertension/drug therapy , Male , Middle Aged , Posture , Rest , Single-Blind Method
6.
Am Heart J ; 121(1 Pt 2): 389-94, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1824665

ABSTRACT

An in vitro assay was used to investigate the effects of doxazosin on the platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate. Platelet-rich plasma from normotensive subjects and patients with hypertension was compared. Doxazosin produced a concentration-dependent inhibition of platelet aggregation in both groups, but significantly lower concentrations were required to inhibit platelet aggregation in plasma taken from patients with hypertension. The concentrations of doxazosin that inhibited platelet aggregation in vitro were similar to those that are used clinically to control blood pressure in patients with hypertension.


Subject(s)
Antihypertensive Agents/pharmacology , Hypertension/blood , Platelet Aggregation Inhibitors , Platelet Aggregation/drug effects , Prazosin/analogs & derivatives , Adult , Blood Platelets/drug effects , Dose-Response Relationship, Drug , Doxazosin , Female , Humans , In Vitro Techniques , Male , Middle Aged , Prazosin/pharmacology
7.
Am Heart J ; 121(1 Pt 2): 395-401, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1824666

ABSTRACT

Eighteen patients with a mean age of 54.7 years were included in the study. All patients had a diagnosis of mild or moderate essential hypertension (sitting diastolic blood pressure of 96 to 114 mm Hg). The study design was single blind and in two phases: phase I, placebo (4 weeks), and phase II, the active treatment (8 weeks) with increasing doses, if needed, of doxazosin every 2 weeks (1, 2, 4, and 8 mg/day). Results show that doxazosin has an antihypertensive effect that is dose dependent. Systolic, diastolic, and mean blood pressures were decreased significantly, and no effect on heart rate was observed. Doxazosin significantly inhibited the platelet aggregation induced by epinephrine, adenosine diphosphate, and collagen in a dose-dependent manner. In addition, treatment with doxazosin lowered total serum cholesterol and triglyceride levels, without changing other standard biochemical parameters. This indicates that doxazosin could offer a distinct therapeutic advantage in the modulation of atherogenic and thromboembolic factors associated with coronary heart disease.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Platelet Aggregation Inhibitors , Platelet Aggregation/drug effects , Prazosin/analogs & derivatives , Antihypertensive Agents/administration & dosage , Cholesterol/blood , Coronary Disease/epidemiology , Dose-Response Relationship, Drug , Doxazosin , Female , Humans , Hypertension/blood , Male , Middle Aged , Prazosin/administration & dosage , Prazosin/therapeutic use , Risk Factors , Single-Blind Method , Thromboembolism/epidemiology
8.
Postgrad Med J ; 67 Suppl 5: S38-40, 1991.
Article in English | MEDLINE | ID: mdl-1839438

ABSTRACT

This study examined the antihypertensive efficacy of open-label amlodipine in once-daily doses of 5-10 mg for 12 weeks. Efficacy was assessed by measurement of blood pressure and heart rate in the supine, seated and standing positions and after exercise periodically during the study. Blood pressure was significantly reduced throughout the study with no change in heart rate. During a placebo-washout phase after the 12-week active treatment phase of the study, blood pressure returned to baseline values. After the 4-week placebo-washout phase some patients received a single 10-mg dose of amlodipine followed by an exercise test 6 h later, which showed that amlodipine lowered blood pressure without blunting the normal physiological response to exercise. In these patients amlodipine also significantly reduced ex vivo platelet aggregation induced by collagen or ADP.


Subject(s)
Calcium Channel Blockers/pharmacology , Hypertension/drug therapy , Nifedipine/analogs & derivatives , Platelet Aggregation/drug effects , Amlodipine , Calcium Channel Blockers/administration & dosage , Drug Administration Schedule , Exercise Test , Female , Heart Rate/drug effects , Humans , Hypertension/physiopathology , Male , Middle Aged , Nifedipine/administration & dosage , Nifedipine/pharmacology , Platelet Aggregation Inhibitors/pharmacology
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