lisinopril and Hypotension

Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.. Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.. 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05).. Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.

Topics: Acute Disease; Aged; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Female; Humans; Hypertension; Hypotension; Labetalol; Lisinopril; Male; Pilot Projects; Stroke; Survival Analysis; Treatment Outcome

To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments.. A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial.. Five hospitals in England.. Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm).. Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm.. The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death.. 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy.. Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Cardiotonic Agents; Cost-Benefit Analysis; Deglutition Disorders; Double-Blind Method; Female; Hospitals; Humans; Hypertension; Hypotension; Infusions, Intravenous; Labetalol; Lisinopril; Male; Middle Aged; Phenylephrine; Placebos; Stroke; Survival Analysis; Time Factors; Treatment Outcome

Angiotensin-converting enzyme (ACE) inhibitors have been reported to be effective in placebo-controlled trials in various subsets of patients with acute myocardial infarction (MI). However, no direct comparisons have been performed between different ACE inhibitors in the same patient population.. This phase III, double-blind, parallel-group, multicenter study compared the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed patients with acute MI. Patients, aged 18 to 75 years, were randomized to receive oral zofenopril (30-60 mg/day) or lisinopril (5-10 mg/day), starting within 12 hours of completion of thrombolytic therapy and continuing for 42 days. The primary study end point was the incidence of severe hypotension (systolic blood pressure <90 mm Hg), either cumulative or drug-related. Secondary end points included additional safety and efficacy parameters.. The overall incidence of severe hypotension was slightly 5 more reduced with zofenopril (10.9%) than with lisinopril (11.7%, P =.38). The incidence of drug-related severe hypotension was slightly but significantly lower with zofenopril than with lisinopril (6.7 vs 9.8%, 2-tailed P =.048). The 6-week mortality rate was 3.2% in the zofenopril group and 4.0% in the lisinopril group (P =.38), and no significant differences were observed in the incidence of major cardiovascular complications or any safety variables between the 2 ACE inhibitors.. The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and associated with a rather low rate of severe hypotension when given in accordance with a dose-titrated scheme to thrombolyzed patients with acute MI. These findings could have a positive clinical impact and increase the proportion of patients with acute MI who can be safely treated with ACE inhibitors.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Double-Blind Method; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Hypotension; Lisinopril; Male; Middle Aged; Myocardial Infarction; Recurrence; Survival Rate

Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria.. In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients.. In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chronic Disease; Diuretics; Dose-Response Relationship, Drug; Female; Hemodynamics; Humans; Hypercholesterolemia; Hypoalbuminemia; Hypotension; Kidney Diseases; Kidney Function Tests; Lisinopril; Longitudinal Studies; Male; Maximum Tolerated Dose; Middle Aged; Proteinuria; Sodium, Dietary; Treatment Outcome; Triglycerides

Many trials have proved the benefits of early systematic treatment with angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction (AMI). Pathophysiological studies, however, suggest potential harm in excessive reduction of blood pressure (BP) in hypertensive patients with ischemic heart disease.. We analyzed data from the GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico) trial to assess the effects of early treatment with angiotensin-converting enzyme inhibitors during AMI in patients with a history of hypertension compared with normotensive patients. The trial randomly assigned 19,394 patients to 6 weeks of lisinopril treatment or control, starting treatment within 24 hours of AMI onset.. In the 10,661 normotensive patients, lisinopril significantly reduced lethal events, but in the 7362 hypertensive patients, a higher rate of lethal events was reported the first day of treatment, and the benefits only appeared subsequently. These results may be attributable to the subgroup of 1165 hypertensive patients with low baseline systolic BP (lower quintile, BP <120 mm Hg), in whom critical hypotension was more prone to develop after lisinopril treatment. In fact, these patients showed a higher mortality rate as the result of an excess of cardiogenic shock during the first day of lisinopril treatment (odds ratio 3.07, 95% CI 1.39-6.77) and a persistent, unfavorable death trend after 6 weeks.. These data suggest that caution should be exercised when using lisinopril in the acute phase of a myocardial infarction in patients with a history of hypertension but low systolic BP at presentation.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Data Interpretation, Statistical; Female; Humans; Hypertension; Hypotension; Lisinopril; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk; Survival Analysis

Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF.. The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction.. Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy.. These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Drug Administration Schedule; Female; Heart Failure; Humans; Hyperkalemia; Hypotension; Kidney Diseases; Lisinopril; Male

To assess whether modifications in the nighttime blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension.. The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600-2400 h), night-time average (2400-0600 h) and day-night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed.. The reproducibility of the day-night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper-non-dipper dichotomy was also low, 35-40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment The changes in left ventricular mass index after 12 months of treatment were significantly (P<0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day-night difference (r= -0.03 and -0.008 for systolic and diastolic blood pressures, respectively).. Our results show that day-night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day-night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Echocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Hypotension; Lisinopril; Male; Middle Aged; Prospective Studies; Reproducibility of Results

The safety and tolerability of lisinopril have been assessed in 1,734 hypertensive patients treated with the agent in a number of clinical trials. Here we compare the clinical and laboratory adverse experiences in younger (under 55 years old) and older (at least 55 years old) patients treated with lisinopril monotherapy. The incidence of adverse experiences in these older patients was similar to that in the younger patients. A comparison also was made of clinical adverse experience data for older hypertensive patients treated either with lisinopril monotherapy or with various control agents (atenolol, metoprolol, and hydrochlorothiazide) in double-blind controlled studies. In these studies, the clinical adverse experience incidences and discontinuation percentages seen in the older patients treated with lisinopril were comparable to the data from the patients treated with the control agents. Thus, lisinopril is generally well-tolerated in older hypertensive patients, and should be considered a therapeutic option in the management of these patients.

Topics: Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Dizziness; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypotension; Lisinopril; Male; Middle Aged

The acute hypotensive response to oral and parenteral enalapril (E) and lisinopril (LI) was assessed in 24 patients with chronic congestive heart failure in two open, randomized, balanced, crossover studies. In the E study, 12 patients received each of three treatments: a single oral dose of 10 mg E, a single intravenous bolus of 5 mg E, and a single intravenous bolus of 5 mg enalaprilat (ET). In the LI study, 12 patients received each of two treatments: a single oral dose of 10 mg LI and a single intravenous bolus of 5 mg LI. Intraarterial blood pressure was measured continuously. Significant decreases from baseline in mean arterial pressure (MAP) were observed in all cases, starting at 15 min. The maximal hypotensive effect (MAP; mean +/- SD) was greatest and the nadir earliest for intravenous ET (-30 +/- 7 mm Hg at 75 min) compared with oral E (-25 +/- 10 mm Hg at 210 min) and intravenous E (-19 +/- 10 mm Hg at 195 min). Oral E and intravenous E had similar onsets of action. The maximal reduction following oral LI (-19 +/- 13 mm Hg at 210 min) was similar to oral E and intravenous E. The effect of intravenous LI (-25 +/- 9 mm Hg at 105 min) was similar to that of intravenous ET. Among the parenteral treatments, E produced the most gradual and least pronounced reduction in blood pressure, and may be best suited for use in the acute situation to minimize the risk of abrupt hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Blood Pressure; Chronic Disease; Enalapril; Enalaprilat; Female; Heart Failure; Humans; Hypotension; Injections, Intravenous; Lisinopril; Male; Middle Aged

Angiotensin-converting enzyme (ACE) inhibitor overdose is an uncommonly presenting toxicologic emergency. Management is primarily supportive care, but a small body of evidence exists to support naloxone for management of hypotension.. We present a case of accidental ACE inhibitor overdose. The patient took approximately 300 mg lisinopril over 48 h and presented for evaluation of syncope. He was hypotensive and unresponsive to fluids. We administered naloxone with immediate and sustained resolution in hypotension. The mechanism of action is briefly discussed. WHY SHOULD AN EMERGENCY MEDICINE PHYSICIAN BE AWARE OF THIS?: Naloxone is a rapid, low-risk, low-cost, and effective intervention for hypotension due to ACE inhibitor toxicity. It is supported by basic science research and clinical experience.

Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Overdose; Humans; Hypotension; Lisinopril; Male; Naloxone

Continuing renin-angiotensin-aldosterone system antagonist therapy on the day of surgery is controversial, and appears to contribute to intraoperative hypotension. A patient presenting for cerebral aneurysm clipping continued her angiotensin-converting enzyme inhibitor on the morning of surgery, and subsequently experienced significant postinduction hypotension that culminated in cardiac arrest. Following successful resuscitation, she returned 6 weeks later to have her aneurysm clipped using identical anesthetic management; her blood pressure medications were held on the day of surgery.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiopulmonary Resuscitation; Female; Heart Arrest; Humans; Hypotension; Intracranial Aneurysm; Intraoperative Complications; Lisinopril

Lisinopril is an angiotensin converting enzyme inhibitor used for treatment of hypertension, congestive heart failure, and acute myocardial infarction. Reports of clinical experience with pediatric ingestions are minimal.. A 13-year retrospective study of lisinopril ingestions in children reported to the California Poison Control System was analyzed and case notes were reviewed. Institutional Review Board approval was obtained and cases were blinded. Inclusion criteria were lisinopril as a single ingestant, age less than 6 years, treatment in a health care facility, case followed to a known outcome.. Inclusion criteria were met in 296 cases. Demographics include 51% of male patients and the mean age was 1.97 years (range: 9 months-5 years). Of the 296 patients, 8 patients (2.7%) developed hypotension (ranges: 55-74 mm Hg systolic and 22-48 mm Hg diastolic). The lowest blood pressure of 55/22 mm Hg was recorded in a 22-month old male who ingested an estimated 120-mg lisinopril (13.3 mg/kg). The lowest dose of lisinopril causing hypotension was with an estimated dose of approximately 50 mg or 3.9 mg/kg in a 2-year old. Two hundred and eighty-two patients (95.3%) were treated and released from the emergency department and 14 patients (4.7%) were admitted. The dose ingested was reported in 189 cases and an exact-dose of lisinopril was reported in 61 patients (20.6%); mean amount ingested was 3.0 mg/kg, median amount ingested was 2.1 mg/kg (range: 0.1-10.9 mg/kg, N = 38); and mean total dose was 33.4 mg, median total dose was 20 mg (range: 2.5-160 mg, N = 61). None of the patients with exact-dose lisinopril ingestions developed hypotension, received intravenous fluids, or were admitted.. The lowest estimated dose of lisinopril to cause hypotension was 50 mg or 3.9 mg/kg. Although continued evaluation of pediatric lisinopril ingestions is essential to determine more specific thresholds of toxicity, the lack of effect on blood pressure in children with exact-dose ingestions indicate that pediatric lisinopril ingestions (for ages > 9 months) ≤ 4 mg/kg up to 40 mg total may be safely managed at home.

Topics: Accidents, Home; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; California; Child, Preschool; Dose-Response Relationship, Drug; Electronic Health Records; Female; Follow-Up Studies; Humans; Hypotension; Infant; Lisinopril; Male; Poison Control Centers; Practice Guidelines as Topic; Retrospective Studies; Severity of Illness Index; Sleep Stages

Angiotensin converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, myocardial infarction, and congestive heart failure. They have a known adverse effect of unresponsiveness to vasoconstrictors resulting in hypotension for the patients undergoing cardiac surgery. We report a case of a 43-year-old female patient with preoperative lisinopril (2.5 mg per day for a week prior to cardiac surgery), who was diagnosed with severe mitral and tricuspid valve regurgitation. She underwent both a mitral and tricuspid valve replacement operation using cardiopulmonary bypass (CPB). To address her ACEI-associated hypotension on cardiopulmonary bypass, bypass flows were as high as cardiac index of greater than 3 (3.1 +/- .2) L/min/m2 to provide sufficient perfusion indicated by cerebral oxymetry monitoring and adequate urine on pump. In addition, due to unresponsiveness to regular concentration of neosynephrine (neo), boluses of higher concentrations up to 320 microg/mL of neo were administered to maintain the perfusion pressure on pump. The patient was weaned from CPB uneventfully and was discharged home on postoperative day 7. Additional therapeutic treatment to ACEI-associated hypotension and unresponsiveness to neo for the patients undergoing cardiac surgery using CPB is reviewed as well in this paper.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiopulmonary Bypass; Female; Humans; Hypotension; Lisinopril; Mitral Valve Insufficiency; Phenylephrine; Tricuspid Valve Insufficiency; Vasoconstrictor Agents

A case of severe bradycardia and hypotension associated with concomitant tizanidine and lisinopril therapy is reported.. An 85-year-old man with a chief complaint of profound weakness was admitted to the hospital with a blood pressure reading of 60/32 mm Hg and a heart rate of 37 beats/min. His medical history included type 2 diabetes mellitus, congestive heart failure, gastroesophageal reflux disease, chronic obstructive pulmonary disease, osteoarthritis, restless leg syndrome, benign prostatic hyperplasia, generalized anxiety disorder with depression, and severe chronic back pain for which he was receiving treatment at a pain clinic. Two days before hospital admission, he had been seen at the pain clinic and started on ti-zanidine. Additional medications included acetaminophen, chlorpromazine, citalopram, finasteride, lidocaine patch, lisinopril, metformin, pramipexole, omeprazole, simvastatin, theophylline, diclofenac topical gel, hydrocodone-acetaminophen, and ondansetron. After taking three doses of the newly prescribed tizanidine, he developed severe hypotension and bradycardia. Notable laboratory test values included a serum creatinine concentration of 1.90 mg/dL, a blood urea nitrogen concentration of 21 mg/dL, a serum potassium concentration of 5.5 meq/L, and a serum sodium concentration of 128 meq/L. Upon admission, tizanidine, lisinopril, theophylline, omeprazole, and simvastatin were withheld, and i.v. fluids were administered. The patient's vital signs began to gradually improve. Within 24 hours, the patient's blood pressure and heart rate had improved, as had the previously abnormal laboratory test values. Tizanidine was discontinued, and all of his other preadmission medications were restarted at discharge.. The addition of tizanidine in a patient receiving long-term treatment with lisinopril was associated with severe hypotension and bradycardia.

Topics: Adrenergic alpha-2 Receptor Agonists; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Bradycardia; Clonidine; Drug Interactions; Humans; Hypotension; Lisinopril; Male; Severity of Illness Index

Topics: Acute Disease; Antihypertensive Agents; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Hypotension; Labetalol; Lisinopril; Stroke; Treatment Outcome

We present a rare case of a 13-year-old girl who took an intentional mixed overdose of nicorandil, lisinopril and metoclopramide. This is the first reported case in the literature of nicorandil overdose in the paediatric age group. The chief presenting clinical signs were hypoxia, peripheral hypoperfusion and hypotension with tachycardia unresponsive to aggressive intravenous volume expansion. Subsequent ECG changes suggested evolving myocardial ischaemia and were accompanied by complaints of back pain and worsening shortness of breath. Vasopressor therapy led to an immediate resolution of the ECG changes and improved the hypotension. This was continued for a further 24 h, until haemodynamic stability was achieved.

Topics: Adolescent; Antihypertensive Agents; Arrhythmias, Cardiac; Drug Overdose; Electrocardiography; Female; Humans; Hypotension; Lisinopril; Nicorandil; Norepinephrine; Suicide, Attempted; Vasoconstrictor Agents

Inhibition of bradykinin metabolizing enzymes (BMEs) can cause acute angioedema, as demonstrated in a recent clinical trial in patients administered the antihypertensive, omapatrilat. However, the relative contribution of specific BMEs to this effect is unclear and confounded by the lack of a predictive pre-clinical model of angioedema.. Rats were instrumented to record blood pressure and heart rate; inhibitors were infused for 35 min and bradykinin was infused during the last 5 min to elicit hypotension, as a functional marker of circulating bradykinin and relative angioedema risk.. In the presence of omapatrilat bradykinin produced dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV (candoxatril+A-899301). However, hypotension was enhanced upon concomitant blockade of APP and further intensified in the presence of NEP inhibition to values not different from omapatrilat alone.. We demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE inhibition alone. Thus, novel BME inhibitors must display no activity against APP to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in patients with diabetes and cardiovascular disease.

Topics: Aminopeptidases; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enzyme Inhibitors; Hypotension; Indans; Lisinopril; Male; Neprilysin; Peptides; Propionates; Pyridines; Rats; Rats, Sprague-Dawley; Thiazepines

The use of combined therapy with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) for treatment of proteinuria has been gaining support. Limited data are available regarding this treatment in the pediatric population. This report describes a case of acute compromise of renal function associated with hypotension in a 7-year-old boy treated with the ACE inhibitor lisinopril and the ARB losartan. It emphasizes the need for close surveillance of renal function and blood pressure during such therapy even in patients with relative preservation of renal function. Further investigation into the utility and safety of dual therapy with an ACE inhibitor plus an ARB in pediatric patients is warranted. Key Words: renal failure, proteinuria, angiotensin-converting enzyme inhibitor, ACEI, angiotensin II receptor blocker, ARB.

Topics: Acute Kidney Injury; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Child; Drug Therapy, Combination; Humans; Hypotension; Lisinopril; Losartan; Male; Proteinuria

To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril.. A 48-year-old woman was admitted due to cerebral hemorrhage at the midbrain and pons, with extension to the fourth ventricle. Consciousness disturbance (Glasgow coma scale 4) with a decerebrate posture improved 5 days after stroke onset. As the BP was fairly high, antihypertensive agents, including lisinopril, were initiated. Three weeks later, the decerebrate rigidity and high BP remained, and tizanidine was initiated to see whether the decrease in muscle tone could facilitate hypertension control and motor recovery. However, the BP dropped dramatically within 2 hours after the first dose of tizanidine. The tizanidine and all of the antihypertensive medications were withdrawn. Tizanidine was used again after her BP had stabilized, but did not produce similar problems.. A similar event was reported in 2000. The reaction in our patient appeared after tizanidine initiation and improved after both lisinopril and tizanidine were discontinued. According to the Naranjo probability scale, this was classified as a possible drug interaction. This kind of reaction is seldom mentioned as occurring during co-administration with tizanidine. With its characteristics, tizanidine has the potential to compromise hemodynamic stability during concomitant angiotensin-converting enzyme inhibitor use.. Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Clonidine; Drug Interactions; Female; Humans; Hypotension; Lisinopril; Middle Aged

Hypotensive reactions have occurred in patients taking angiotensin converting enzyme (ACE) inhibitors after infusion of blood previously in contact with negatively charged surfaces capable of generating kinins, which accumulate when ACE, a kininase, is inhibited. A patient with anomalous bradykinin (BK) metabolism who experienced hypotension during extracorporeal staphylococcal protein A (SPA) therapy while on an ACE inhibitor was studied.. A patient with mitomycin-associated hemolytic-uremic syndrome received SPA treatments after her ACE inhibitor, lisinopril, was held. Lisinopril was restarted before her 18th SPA treatment, and immediately after return of treated plasma she developed facial redness and hypotension, which resolved after the return stopped and recurred when restarted. To study formation and degradation of kinins, exposed her plasma to glass beads. We found a normal kinin formation rate but an abnormal degradation and accumulation of Des-Arg9-BK. The kinin degradation enzymes ACE, aminopeptidase P (APP), and carboxypeptidase N (CPN) were measured while on an ACE inhibitor, showing absence of ACE activity, low APP, but normal CPN.. This patient's vasodilation and hypotension during SPA therapy was associated with a pre- existing anomaly of BK metabolism. Her ACE inhibitor shifted degradation toward Des-Arg9-BK formation, and her low APP was associated with a prolonged t50 and accumulation of the vasoactive Des-Arg9-BK.

Topics: Acute Disease; Aminopeptidases; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Asthma; Bradykinin; Doxorubicin; Female; Flushing; Glass; Hemolytic-Uremic Syndrome; Humans; Hypertension; Hypotension; Immunosorbent Techniques; Leiomyosarcoma; Lisinopril; Lung Neoplasms; Metalloendopeptidases; Microspheres; Middle Aged; Mitomycin; Staphylococcal Protein A; Static Electricity; Uterine Neoplasms; Vasodilation

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Hypotension; Lisinopril; Perindopril

Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.

Topics: Adrenergic alpha-Agonists; Angiotensin-Converting Enzyme Inhibitors; Child; Clonidine; Drug Interactions; Humans; Hypertension; Hypotension; Lisinopril; Male; Muscle Spasticity

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

Topics: Acute Disease; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output; Catecholamines; Female; Hypotension; Lisinopril; Male; Oncorhynchus mykiss; Papaverine; Parasympatholytics; Radioimmunoassay; Renin-Angiotensin System; Reproducibility of Results; Vascular Resistance

The contributions of circulating angiotensin II (Ang II) and catecholamines to cardiovascular control in the spiny dogfish were investigated by monitoring the effects of exogenous and endogenous dogfish [Asn1, Pro3, Ile5]-Ang II (dfAng II) on plasma catecholamine levels and blood pressure regulation. Bolus intravenous injections of dfAng II (30-1200 pmol kg-1) elicited dose-dependent increases in plasma adrenaline and noradrenaline concentrations, caudal artery pressure (PCA), and systemic vascular resistance (RS), and a decrease in cardiac output (Q). Similar injections of Ang II in dogfish pre-treated with the alpha-adrenoceptor antagonist yohimbine (4 mg kg-1) also elicited dose-dependent increases in plasma catecholamine levels yet the cardiovascular effects were abolished. Dogfish treated with yohimbine were hypotensive and had elevated levels of plasma Ang II and catecholamines. Intravenous injection of the smooth muscle relaxant papaverine (10 mg kg-1) elicited a transient decrease in PCA and RS, and increases in plasma Ang II and catecholamine levels. In dogfish first treated with lisinopril (10(-4) mol kg-1), an angiotensin converting enzyme inhibitor, papaverine treatment caused a more prolonged and greater decrease in PCA and RS, an attenuated increase in plasma catecholamines, and no change in plasma Ang II. By itself, lisinopril treatment had little effect on PCA, and no effect on RS, plasma Ang II or catecholamines. In yohimbine-treated dogfish, papaverine treatment elicited marked decreases in PCA, RS, and Q, and increases in plasma Ang II and catecholamines. Among the three papaverine treatments, there was a positive linear relationship between plasma Ang II and catecholamine concentrations, and the cardiovascular and hormonal changes were most pronounced in the yohimbine + papaverine treatment. Therefore, under resting normotensive conditions, while Ang II does not appear to be involved in cardiovascular control, catecholamines play an important role. However, during a hypotensive stress elicited by vascular smooth muscle relaxation. Ang II indirectly contributes to cardiovascular control by dose-dependently stimulating catecholamine release.

Topics: Adrenergic alpha-Antagonists; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Physiological Phenomena; Dogfish; Epinephrine; Female; Hypotension; Lisinopril; Male; Norepinephrine; Papaverine; Parasympatholytics; Yohimbine

The increasing usage of ACE-inhibitors in the treatment of hypertension and chronic heart failure may increase the incidence of adverse anaesthetic occurrences. Four such cases are described. In two of these cases, the patient reacted with severe hypotension when general anaesthesia was supplemented with epidural bupivacaine. Another patient suffered a heart fatality after severe hypotension in conjunction with the administration of a spinal anaesthetic. Finally, one patient suffered sudden fatal pulmonary oedema after completion of uneventful general anaesthesia, possibly due to late resumption of ACEI-treatment. The cases are discussed in detail, with particular reference to the possible underlying mechanisms. Preoperative discontinuation of ACEI-treatment is controversial. We present some of the issues involved. Most authors lean towards continuing ongoing treatment, even though there is firm evidence that this increases the risk of hypotensive episodes due to hypovolaemia, arguing that such events may be predicted and antagonized with fluid therapy.

Topics: Aged; Anesthesia, General; Anesthetics, General; Angiotensin-Converting Enzyme Inhibitors; Captopril; Fatal Outcome; Female; Humans; Hypotension; Lisinopril; Male; Middle Aged; Preanesthetic Medication

We present the case of a 60 year old C6 complete tetraplegic patient who developed profound hypotension following initiation of the angiotensin-converting enzyme inhibitor lisinopril to control blood pressure. Other causes of hypotension, such as myocardial infarction and sepsis was ruled out. Inhibition of the renin-angiotensin-aldosterone system was the probable cause of hypotension. This case demonstrates the critical importance of the renin-angiotensin-aldosterone axis in the maintenance of blood pressure in tetraplegic patients, who may lack input from the brain to sympathetic neurons, and therefore have increased reliance on the renin-angiotensin-aldosterone axis for the maintenance of blood pressure. Angiotensin-converting enzyme inhibitors should be avoided in tetraplegic patients, unless other treatment modalities are ineffective.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Humans; Hypotension; Lisinopril; Male; Middle Aged; Obesity; Quadriplegia

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Humans; Hypotension; Kidney Tubular Necrosis, Acute; Lisinopril; Male

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Dipeptides; Heart Failure; Humans; Hypotension; Indoles; Lisinopril; Middle Aged; Perindopril

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.

Topics: Adult; Age Factors; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Heart Failure; Hematologic Tests; Humans; Hypertension; Hypotension; Kidney Diseases; Lisinopril; Male; Middle Aged