Angiotensin‐Converting Enzyme Inhibitors: Mechanistic Controversies

Ujhelyi, Michael R.; Ferguson, Roger K.; Vlasses, Peter H.

doi:10.1002/j.1875-9114.1989.tb04149.x

Cited by 29 publications

(8 citation statements)

References 89 publications

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“…The authors suggest that recently identified renin-angiotensin systems in the brain may be involved in control of thirst and sodium and water handling, and note that ACE inhibitors may also affect renal homeostatic mechanisms mediated by prostaglandins. There is considerable controversy surrounding the importance of these systems, however (Ujhelyi et al 1989). The complicated illness of this patient makes evaluation difficult, and even the rechallenge with lisinopril is not conclusive because of the confounding effect of liberalised fluid intake.…”

Section: Sodium and Potassium Balancementioning

confidence: 97%

Adverse Effects of Angiotensin Converting Enzyme (ACE) Inhibitors

Parish

Miller

1992

Drug Safety

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The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Sodium and Potassium Balancementioning

confidence: 97%

Adverse Effects of Angiotensin Converting Enzyme (ACE) Inhibitors

Parish

Miller

1992

Drug Safety

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“…Initially, the pharmacologic effects of ACE inhibitors were believed to be the result of inhibiting the formation of angiotensin II, a potent vasoconstrictor and stimulus for the secretion of aldosterone. 8,9 This process results in vasodilation and naturesis. It is now recognized that their pharmacologic activity extends to the kallikrein-kinin and prostaglandin systems.…”

Section: Case Reportmentioning

confidence: 98%

“…More importantly, however, the existence of tissue renin-angiotensin systems has been identified in the aorta, renal cortex, and in several areas of the brain. 9 Within the central nervous system, angiotensin II may be involved in the physiology of thirst and sodium appetite, as well as with the endocrine functions of the pituitary and the central control of blood pressure.…”

Section: Case Reportmentioning

confidence: 99%

Severe Hyponatremia: An Association with Lisinopril?

Hume

Jack²,

Levinson³

1990

DICP

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A 63-year-old white woman with a history of hypertension and chronic obstructive pulmonary disease presented to the emergency room with worsening shortness of breath, anorexia, coughing, increased thirst, and leg edema of two weeks' duration. Medications included lisinopril 10 mg/d, which had been started six weeks earlier, sustained-release theophylline 300 mg q12h, and an albuterol inhaler. The lisinopril was discontinued on admission. Serum sodium concentration was 109 mmol/L; the osmolality of the blood and of the urine were 253 mOsmol and 438 mOsmol, respectively, with a specific gravity of 1.025 and a urine sodium of 17 mmol/L. The hyponatremia initially was considered to be the syndrome of inappropriate antidiuretic hormone secretion in response to the patient's suspected pneumonia. Due to worsening blood pressure, lisinopril was restarted and the serum sodium concentration dropped from 134 to 126 mmol/L. Evaluation of the patient's hyponatremia included assessment of thyroid, adrenal, hepatic, and cardiac function that were within normal limits. The patient was discharged on the following medications: sustained-release theophylline 300 mg tid, prednisone 10 mg/d, albuterol inhaler 2 puffs q6h, and sustained-release verapamil 240 mg/d for blood pressure control. Her serum sodium concentration has remained between 135 and 140 mmol/L during hospitalizations for exacerbations of chronic obstructive pulmonary disease and for pneumonias 10 and 12 months after discharge.

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“…167 The rash appears to be dose-related. 77 Other ACE inhibitors may cause a rash with a much lower frequency than captopril, 98 and there does not appear to be cross-reactivity among ACE inhibitors.…”

Section: Brown and Vaughan April 14 1998mentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibitors

1998

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Abstract-ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT 1 receptor antagonists. MechanismACE, or kininase II, is a bivalent dipeptidyl carboxyl metallopeptidase present as a membrane-bound form in endothelial cells, in epithelial or neuroepithelial cells, and in the brain and as a soluble form in blood and numerous body fluids. 1 ACE, or kininase II, cleaves the C-terminal dipeptide from Ang I and bradykinin and a number of other small peptides that lack a penultimate proline residue. Thus, ACE is strategically poised to regulate the balance between the RAS and the kallikrein-kinin system.The RAS plays a pivotal role in blood pressure regulation (Fig 1). Reduced sodium delivery at the macula densa, decreased renal perfusion pressure, and sympathetic activation all stimulate secretion of renin by the juxtaglomerular cell, the classic source of renin in the circulating RAS.

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Angiotensin‐Converting Enzyme Inhibitors: Mechanistic Controversies

Cited by 29 publications

References 89 publications

Adverse Effects of Angiotensin Converting Enzyme (ACE) Inhibitors

Adverse Effects of Angiotensin Converting Enzyme (ACE) Inhibitors

Severe Hyponatremia: An Association with Lisinopril?

Angiotensin-Converting Enzyme Inhibitors

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