Hypotension During Administration of Angiotensin Converting Enzyme Inhibitor SQ 20,881 (original) (raw)
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Changing Concepts in the Management of Hypertension
Medical Journal of Australia, 1975
Experience in a hypertension clinic attended by 591 patients over a 13-year period has shown marked changes in the pattern of use of hypotensive agents. Thiazides have been used throughout the period in almost all cases. Methyldopa was used for most patients for almost a decade. Since 1967 there has been a steady increase In the use of beta adrenergic blocking agents, and these are now used for over 60% of patients attending the clinic. Combination beta adrenergic blocking agents with peripheral vasilodators such as hydraHazlne and prazosln have provided a very effective means of controlling the blood pressure in moderate and severe hypertension. Prazosin, a new peripheral vasodilator, has been used in the treatment of 295 patients. In most cases It has been used In combination with a thiazide diuretic and beta adrenergic blocking agent. Open studies have demonstrated that this Is an effective hypotensive agent. Side effects are few and are counteracted by combination with a beta adrenergic blocking agent. Prazosin and hydrallazine are being compared in dcuble-bllnd studies. ALTHOUGH there are conflicting views about the levels of systolic and diastolic blood pressure at which treatment should commence, rio-one would doubt that severe hypertension should be treated. In defining "severe" hypertension, it is important to realize that, whereas blood pressure measurements which are obtained in the conventional fashion are the most convenient and most widely applied criteria of severity, they are not necessarily the best. The level of the blood pressure is certainly not the only factor which determines progressive vascular disease and organ damage even in malignant hypertenston." In this era of therapeutic enthusiasm and widespread
Current Treatment of Patients with Hypertension
Drugs, 2003
Epidemiological studies have shown that both vascular events, especially among elderly patients systolic and diastolic blood pressure values are di-with isolated systolic hypertension [8,9] or systo-diasrectly and linearly related to the risk of cardio-tolic hypertension. [10] (although in reference 9 and vascular events, and that this relationship is still 10 randomisation was performed according to an detectable for blood pressure values within the nor-alternative scheme). Moreover, a recent overview of mal range. Although blood pressure values are placebo-controlled trials with calcium channel antstrong determinants of the risk of cardiovascular agonists has concluded that, although there is no events, the presence of end-organ damage as well as clear evidence of reductions in coronary artery disthe association with other cardiovascular risk factors ease or heart failure, the estimates of treatment further increases the risk of cardiovascular effects do not exclude the existence of a beneficial events. Therefore, when planning treatment for effect on these major cardiac outcomes and largely patients with hypertension, current guidelines em-preclude the occurrence of adverse effects (includphasise the relevance of risk stratification, based on ing cancer or uncontrolled bleeding). [6,11] However, blood pressure values, the presence of end-organ it is still controversial whether different treatment damage or other cardiovascular risk factors. regimens based on different drug classes can offer additional advantages, beyond a similar degree of Controlled clinical trials have shown the benefit blood pressure control, in the prevention of cardioof blood pressure reduction, which is detectable in vascular morbidity and mortality. young, middle aged and elderly patients, both male and female, with severe, moderate and mild hyper-
Circulation, 2001
A ngiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of "functional renal insufficiency" and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor-induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Renal and Systemic Effects of Ang II During Volume Depletion and CHF Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs. 1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in hypovolemia or CHF), the sympathetic nervous system is activated and renin is secreted from juxtaglomerular cells of afferent arterioles, with consequent Ang II production. At the level of the renal glomerulus, Ang II can be expected to cause vasoconstriction of postglomerular efferent to a much greater degree than preglomerular afferent arterioles. This imbalance of effect on the efferent arteriolar circulation restores glomerular capillary pressure and thereby maintains glomerular filtration despite reduced perfusion pressure. Under these circumstances, filtration fraction (GFR/ renal plasma flow) increases, which favors proximal tubular Na ϩ reabsorption. Ang II also independently promotes proximal tubule Na ϩ reabsorption and, through its effect on aldosterone synthesis, collecting duct Na ϩ reabsorption. 2 In the presence of excess Ang II, as in CHF, urinary Na ϩ excretion can be expected to fall dramatically, although other factors, such as low blood pressure, make important contributions to the antinatriuretic state that is characteristic of CHF. Ang II is also a proven dipsogen (that is, an agent that induces thirst) in experimental animals because of an effect on central thirst centers. An increase in water intake may be explained in part by the physiologically inappropriate thirst drive in CHF. 3 In volumedepleted normal individuals, these mechanisms preserve ECF volume by curbing additional losses, and taken together, they The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee in June 2001. A single reprint is available by calling 800-242-8721
Drugs in the management of hypertension. Part III
American Heart Journal, 1976
The vasodilator drugs act directly on vascular smooth muscle to produce vasodilatation and reduction in peripheral resistance. They include hydralazine, diazoxide, minoxidil, guancydine, and sodium nitroprusside. With the exception of sodium nitroprusside, these drugs have a selective effect on arterioles with little if any effect on venous capacitance vessels. This selective dilatation of arterioles results in an increase in venous return, which triggers a reflex increase in heart rate and stroke volume mediated through the sympathetic nervous system. As a result they share several common side effects due to increased cardiac action. These include palpitation, headache, and the capacity to precipitate angina pectoris in patients with coronary disease. In addition, drugs in this group share an ability to stimulate renin release and promote sodium retention. Increased cardiac output and sodium retention both act to reduce the hypotensive effects of vasodilatation. In most circumstances, drugs in this group should be use d together with propranolol and diuretics which counteract these effects, enhance the effectiveness of vasodilatation, and minimize side effects. Of the vasodilators, only hydralazine is available for oral use in the United States at present. Minoxidil and guancydine have given promising results in clinical trials. Diazoxide and sodium nitroprusside are available only for intravenous use, although diazoxide has been shown to be effective given orally, s:~
Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme
British Medical Journal, 1979
and conclusions Captopril, a specific oral inhibitor of angiotensinconverting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may
Angiotensin-converting enzyme inhibition, catecholamines and hemodynamics in essential hypertension
American Journal of Cardiology, 1982
Captopril was given to 15 unselected patients with essential hypertension (WHO II) at a dose range of 300 to 600 mg/day. Hemodynamic indexes (thermodilution) as well as levels of plasma norepinephrine, epinephrine, renin activity and aldosterone were determined simultaneously at the end of 2 weeks of placebo and after 8 weeks of captopril treatment. Systolic and diastolic arterial pressures were reduced significantly by treatment both supine (p <0.0025) and standing (p <0.0025). The diastolic arterial pressure was normalized (less than 95 mm Hg) in five patients and significantly reduced in four, whereas six patients were considered poor responders (mean arterial pressure decrease 10 mm Hg or less). The decrease in arterial pressure correlated significantly with the reduction in total peripheral resistance (r = 0.71), whereas cardiac index did not change and stroke index increased because of a slight decrease of heart rate. Plasma and urinary norepinephrine and epinephrine did not change during treatment. Moreover, the response of both heart rate and plasma catecholamines to upright posture was not altered by captopril treatment. Plasma renin activity increased and plasma aldosterone concentration decreased during treatment. These results suggest that inhibition of converting enzyme activity by captopril induces a reduction in arterial pressure through a reduction in total peripheral resistance. There was no evidence of an appreciable reduction in sympathetic nervous system activity during therapy.
T he lessons learned from studies in humans and animals using angiotensin-converting enzyme (ACE) inhibitors showed the existence of alternate mechanisms for angiotensin II (Ang II) generation, through either ACE escape or direct conversion of Ang I to Ang II by chymase. These findings led to exploring the utility of therapies in which ACE inhibitors and Ang II type1 receptor (AT 1 R) blockers were combined to optimize renin-angiotensin system (RAS) blockade. 1 Although the rationale for blocking the system at multiple foci was compelling, the increased risk of acute dialysis and hyperkalemia found in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) 2 discouraged this therapeutic approach. 3 The introduction of an orally active direct renin inhibitor created an opportunity to bypass the large reactive increase in renin secretion induced by interruption of the Ang II negative feedback on renin release. 4 Although aliskiren hemifumarate, the first orally effective direct renin inhibitor for the treatment of hypertension, showed efficacy as an antihypertensive agent and in target organ protection, it failed to suppress Ang II formation as the valsartan-aliskiren combination was more effective than each drug alone. 5 Enthusiasm for combined blockade of either ACE inhibitors or direct renin inhibitor with AT 1 R blocker is now further questioned given the recent halting of the Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (ALTITUDE) trial, 6 in which patients receiving the combination of aliskiren with either valsartan or an ACE inhibitor (http://www.theheart. org/article/1331173.do) experienced an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension over 18 to 24 months of follow-up. 7
Hypertension, 1984
The antihypertensive, hemodynamic, and humoral effects of the new convertingenzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 months of uninterrupted treatment (20 mg twice daily) in 10 hypertensive patients. Six achieved good blood pressure (mean arterial pressure) control with enalapril alone (from 126 ± 7.0 mm Hg pretreatment to 105 ± 1.6 mm Hg at 3 months, p < 0.05). The other four required the addition of diuretics (hydrochlorothiazide 25 mg orally twice daily) at different stages of follow-up, with resultant blood pressure control (128 ± 9.6 mm Hg pretreatment to 113 ± 1.9 mm Hg at 2 months after the addition of diuretics). Neither the acute nor long-term blood pressure response could be predicted from the pretreatment levels of plasma renin activity. The blood pressure reduction during enalapril therapy was characterized by a decrease in total peripheral resistance (53 ± 2.5 U-M 2 pretreatment to 38 ± 3.0 U-M 2 at 3 months, p < 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroceptor dysfunction since the response to head-up tilt (the increase in diastolic blood pressure, in heart rate, and in plasma catecholamines) was normal and not significantly different from pretreatment response. Average blood volume did not change (91% ± 4.3% of normal in the pretreatment period to 93% ± 2.9% after 3 months of therapy, p = NS) despite the significant lowering of arterial pressure with enalapril alone (n = 6). This could have been possibly related to the reduction in plasma aldosterone (12.6 ± 2.3 to 8 ± 0.9 ng/dl, p < 9.95) induced by treatment. In conclusion, the hemodynamic consequences of blood pressure reduction by enalapril were similar to those produced by other converting-enzyme inhibitors and angiotensin II antagonists. These findings suggest that the hemodynamic effects of enalapril were related to interference with the generation of angiotensin II rather than a direct action of the drug.