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

Prazosin kinetics were studied after single doses (intravenous and oral, 0.5 mg) and after increasing multiple doses (0.5 to 5 mg three times daily) in eight patients with hypertension. After intravenous administration the kinetics could be described by a linear two-compartment open model. Terminal half-life (t1/2 beta) was about 3 hr and apparent volume of distribution (Vd beta) about 0.6 l/kg. After oral doses bioavailability ranged between 55% and 82%. Since total plasma clearance was low (0.14 l/kg x hr) incomplete bioavailability was the result of incomplete absorption rather than of first-pass liver metabolism. The estimated extraction ratio was about 14%. Renal clearance was negligible; only 1% to 2% of the dose was recovered unchanged in urine. Binding to plasma proteins to both albumin and alpha 1-acid glycoprotein was substantial (97%), with albumin being most important. Increasing multiple doses showed that prazosin followed first-order kinetics with a linear correlation between dose and steady-state plasma concentration (P less than 0.001). There were substantial variations in plasma concentrations between patients and there were also day-to-day variations in concentration within the same patient.
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PMID:Prazosin kinetics in hypertension. 728 77

Although the relationship between blood pressure and cardiac performance has been widely recognized, there are few published clinical observations concerning the effect of blood pressure control on cardiac function. We evaluated the effect of prazosin, an antihypertensive agent which also improves hemodynamic measurements in normotensive patients with heart failure, in 16 patients with moderate hypertension and reduced ejection fractions. Therapy with digoxin and diuretics was continued throughout the study, but other antihypertensive agents were withdrawn at least one week prior to the initiation of the study. Measurements of ejection fraction, cardiothoracic ratio and the duration of maximal treadmill exercise were made before and after two months of antihypertensive therapy with prazosin. On prazosin, blood pressure fell from a mean of 169/103 to 141/84. Excellent control was achieved in 13/16 patients and significant reductions were noted in the remaining three. Concomitantly, ejection fraction rose from .38 +/- .02 (SEM) to .43 +/- .03 (P less than .02), cardiothoracic ratio decreased from .55 +/- .02 to .53 +/- .02 (P less than .05) and exercise capacity increased from 9.2 +/- 0.9 to 11.9 +/- 1.1 minutes (P less than .005). Prazosin was well tolerated except in one patient who experienced worsening angina. These findings emphasize the importance of rigorous blood pressure control in hypertensive patients with left ventricular dysfunction and indicate that prazosin is effective in this setting.
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PMID:Antihypertensive therapy with prazosin in patients with left ventricular dysfunction. Improvement in cardiac performance and exercise tolerance. 730 90

Prazosin, an antihypertensive agent that reduces blood pressure (BP) mainly through a blockade of alpha-adrenergic receptors, may, in theory, affect sympathetic control of circulation to an extent that impairs circulatory hemeostasis. This possibility was studied in subjects with essential hypertension by examining the cardiovascular effects of several stimuli that induce a powerful and diversified activation of the sympathetic noradrenergic activity (dynamic and isometric exercise, cold exposure) and of stimuli that exert a powerful inhibitory influence upon the sympathetic nervous system (carotid baroreceptor reflex). Before and after 15 days of continuous administration of prazosin (2-5 mg), 3 times a day, measurements were made of BP (intraarterial catheter), heart rate, cardiac output (thermodilution), and peripheral resistance. Prazosin reduced mean arterial pressure (10%) and peripheral resistance (9%) at rest, and it did not affect heart rate and cardiac output. Neurally mediated changes in arterial pressure, cardiac output, and peripheral resistance during dynamic or isometric exercise and cold exposure were unaffected by the drug; also unaffected were the cardiovascular responses to increase and decrease in carotid baroreceptor activity obtained by varying carotid transmural pressure through a variable neck pressure chamber device. Thus, the hypotensive and vasodilating effect of prazosin in essential hypertension is not accompanied by an impaired response to neural excitation influences upon the cardiovascular system. Also, the inhibitory influences originating from the carotid baroreflex are unchanged. These data indicate that circulatory homeostasis is largely preserved during administration of prazosin at clinically effective doses.
Hypertension
PMID:Effects of prazosin on autonomic control of circulation in essential hypertension. 741 71

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.
Hypertension 1995 Apr
PMID:Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors. 772 91

The present study investigates sympathetic cotransmission and its alpha-adrenoceptor-mediated modulation in kidneys of spontaneously hypertensive rats (SHR, 12 to 14 weeks) and age-matched normotensive Wistar-Kyoto rats (WKY). In the presence of cocaine and corticosterone, renal nerve stimulation at 1 Hz (30 seconds) induced a greater outflow of norepinephrine in SHR (4.2 +/- 0.2 pmol/g kidney) than in WKY (3.0 +/- 0.2 pmol/g kidney). The alpha 2-adrenoceptor antagonist rauwolscine (0.01 to 1 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in SHR than in WKY. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.03 to 3 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in WKY than in SHR. This difference was not observed in the presence of the P1-purinoceptor antagonist 8-(p-sulfophenyl)theophylline (100 mumol/L). Stimulation at 4 Hz (30 seconds) induced an outflow of ATP (SHR, 12.7 +/- 3.3 pmol/g kidney; WKY, 16.7 +/- 2.1 pmol/g kidney; perfusion solution without cocaine and corticosterone). Prazosin (0.03 mumol/L) markedly reduced pressor responses to stimulation and inhibited the induced ATP outflow by 60% to 70%. When prazosin (0.03 mumol/L) was present, rauwolscine (0.1 mumol/L) increased the induced outflow of norepinephrine and ATP and markedly enhanced prazosin-resistant pressor responses. These pressor responses were abolished by the P2-purinoceptor antagonist suramin (300 mumol/L). The results demonstrate an increased alpha 2-adrenoceptor-mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Jun
PMID:Alpha-adrenoceptor modulation of norepinephrine and ATP release in isolated kidneys of spontaneously hypertensive rats. 776 66

Our aim was to assess clinically whether there was any benefit in adding a single dose of sublingual nifedipine (a slow calcium channel blocker) to prazosin in the management of the cardiovascular manifestations of envenoming by the Indian red scorpion (Mesobuthus tamulus). A total of 163 patients stung by this species was admitted to hospital at Mahad between January 1991 and October 1993. Cardiovascular abnormalities were hypertension (59), of whom 42 had bradycardia and 17 had tachycardia; pulmonary oedema (14), of whom eight had hypertension and six hypotension; supraventricular tachycardia (eight), of whom three had hypotension and one died. Of the remaining patients, 78 demonstrated severe excruciating local pain at the site of sting but had no systemic involvement. Nineteen patients with hypertension and tachycardia were given a single dose of sublingual nifedipine plus prazosin on admission, then prazosin alone repeated 6 hourly. Five patients with massive life-threatening pulmonary oedema recovered after being given intravenous sodium nitroprusside. Prazosin alone helped to alleviate cardiovascular manifestations in the remaining 52 victims. One patient was admitted in a deep coma, 12 hr after the sting, and died. Eight victims whose blood pressure had been controlled in hospital by nifedipine plus prazosin developed acute pulmonary oedema necessitating additional doses of prazosin for recovery. Fifty-two victims treated with prazosin alone did not develop pulmonary oedema and the drug appeared to hasten the recovery. In the presence of high blood pressure, tachycardia, a murmur and impending myocardial failure, nifedipine appeared to contribute to cardiopulmonary instability and to augment myocardial oxygen consumption. In this situation calcium channel blockers should probably be avoided.
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PMID:Vasodilators: scorpion envenoming and the heart (an Indian experience). 780 38

This review summarizes the current approach to antihypertensive therapy in children. It focuses on newer drugs, taking into account changes in clinical practice that have occurred since publication of the second Task Force report. Non-pharmacological therapy, including weight reduction, exercise, and dietary intervention, has great potential for the effective reduction of blood pressure. It should be introduced not only in patients with "significant" hypertension, but also in the care of patients with high normal blood pressure and to complement drug therapy for patients with "severe" hypertension. The goal of antihypertensive drug therapy is reduction of blood pressure to a level below the 95th percentile for age and sex. Attempts to rapidly achieve normal blood pressure immediately after starting therapy are contraindicated. The objective of emergency treatment is prevention of hypertension-related adverse events, and this usually requires only a modest reduction in blood pressure. Nifedipine has become the most commonly used drug for emergency treatment of asymptomatic children. Exceptionally severe elevations of blood pressure or the presence of symptoms should be treated with more potent intravenous drugs. The converting enzyme inhibitors and calcium channel blockers currently are the primary agents for chronic treatment of hypertension in children. Diuretics are usually reserved for hypertensive patients with renal disease. beta-Adrenergic blocking drugs also are effective but have a number of potential adverse effects. Prazosin generally is used as a second-line agent, if the above-noted drugs are ineffective. Although minoxidil is still one of the most effective antihypertensive agents, its associated adverse effects have limited its usefulness.
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PMID:Treatment of hypertension in children. 781 13

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.
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PMID:Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats. 789 82

Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adverse effects of alpha 1-adrenergic blocking drugs. 791 78

Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured in 53 hypertensive patients (26 renally impaired, 27 with normal renal function) before and after treatment with sufficient bunazosin retard or prazosin to control their high blood pressure. After a 3-week placebo run-in period, patients were classified as normal (creatinine clearance > 80 ml/min) or renally impaired (20-55 ml/min), and randomly assigned to bunazosin retard or prazosin. There followed a dose titration (T) phase of 6-7 weeks, and a maintenance (M) phase of 4 weeks. Blood pressure was satisfactorily controlled (sitting diastolic pressure < or = 90 mmHg or decreased by > or = 10 mmHg) by both drugs in both groups. Bunazosin Retard was associated with increases in GFR and ERPF in both normal and renally impaired groups; the increases were statistically significant in the renally impaired group (n = 14). Prazosin was associated with small decreases in both measures in both groups. One patient died of myocardial infarction during the placebo run-in. There were no other serious adverse events. Four patients reported dizziness (2 with each drug). We conclude that with appropriate dose titration, bunazosin retard is well tolerated and preserves renal blood flow when used to treat hypertension in patients with renal insufficiency.
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PMID:Renal haemodynamic effects of bunazosin retard and prazosin in mild to moderately hypertensive patients with normal or moderately impaired renal function. 797 85


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