Drug-induced pseudo-Sezary syndrome: a case report and literature review.

Pseudo-Sezary syndrome is a benign lymphoproliferative disorder, which clinically and pathologically mimics true Sezary syndrome. In this article, a case of pseudo-Sezary syndrome and review the literature has been reported. The patient was a 51-year-old man who developed erythroderma and palmoplantar keratoderma. The patient's medication history included fosinopril and combination metoprolol/hydrochlorothiazide. Flow cytometry showed a population of 2500 "Sezary-like" CD4726 T cells per microliter in the peripheral blood. Skin biopsy showed numerous atypical lymphocytes with epidermotropism, and there was matching dominant T-cell clonality in the skin and peripheral blood. After stopping all antihypertensive medications, the eruption resolved in its entirety.

Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.

Combination therapy with angiotensin-converting enzyme inhibitors and indapamide impairs glucose tolerance in Chinese hypertensive patients.

BACKGROUND: Elevated blood glucose (BG) induced by antihypertensive agents increases the risk of cardiovascular events. This study was designed to investigate whether fosinopril+indapamide combination therapy has any effect on glucose tolerance (GT), and if it did, whether conversion to fosinopril alone could reverse the impaired GT. METHODS: Included in the present study were 124 hypertensive patients, of whom 62 patients were treated with fosinopril plus indapamide (F/I group) and the remaining 62 patients were treated with fosinopril alone (F group). Of them, 89 patients completed a mean of 14-month follow-up. In the F/I group, 29 patients were converted to the use of fosinopril for 4-12 months after they completed the follow-up. RESULTS: In the F group, fasting BG decreased significantly from 5.1+/-0.5 to 4.8+/-0.7 mmol/l (p<0.01), and 2-h postprandial BG decreased significantly from 7.2+/-1.6 to 6.4+/-1.4 mmol/l (p<0.01), while in the F/I group, fasting BG increased significantly from 5.1 +/-0.6 to 5.3+/-0.9 mmol/l (p<0.05), and 2-h postprandial BG increased significantly from 7.2+/-1.7 to 7.7+/-1.8 mmol/l (p<0.05). In 29 patients of the F/I group who completed the follow-up and were converted to fosinopril, fasting BG decreased significantly from 5.5+/-1.0 to 5.3+/-1.0 mmol/l (p<0.05), and 2-h postprandial BG decreased significantly from 7.5+/-2.0 to 7.0+/-2.7 mmol/l (p<0.05). CONCLUSION: Fosinopril+indapamide combination therapy impaired GT in Chinese hypertensive patients, and fosinopril alone was able to reverse fosinopril+indapamide-induced GT impairment in part of these patients.

Successful treatment of fosinopril-induced severe cholestatic jaundice with plasma exchange.

OBJECTIVE: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. CASE SUMMARY: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. DISCUSSION: Angiotensin-converting enzyme (ACE) inhibitor-induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor-induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. CONCLUSIONS: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.

Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension.

A 31-year-old woman developed bilateral posterior ischemic optic neuropathy and infarctions of the cerebral arterial border zones and spinal cord after correction of malignant hypertension. Although a few reports have described patients with neurologic abnormalities after treatment of malignant hypertension, full clinical and neuroimaging documentation of this combination of findings has not occurred. This case report suggests that the relative hypotension of autoregulatory failure induced by treatment of malignant hypertension may give rise to these neurologic complications.

Anemia por fosinopril / Anemia induced by fosinopril

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[Hyperkalemia in hypertensive patients undergoing regular hemodialysis during enalapril and fosinopril therapy].

INTRODUCTION: Hypertension is evident in 80%-85% of patients with chronic renal failure and antihypertensive therapy is needed in 25%-30% of patients. Apart from antihypertensive effect, ACEi's decrease the left ventricular hypertrophy and mortality in dialysis patients. Even so, their use is limited due to hyperkalemia. OBJECTIVE: The objective of the study was to compare the effect of fosinopril and enalapril on serum potassium level in hypertensive hemodialysis patients. METHOD: Prospective pilot study included 16 patients undergoing chronic hemodialysis, with mean age of 58.9 +/- 9.6 years and mean duration of hypertension 11.3 +/- 7.1 years. The effect of antihypertensive drugs of equivalent dose was followed during three periods (three months each): period 1 (therapy with enalapril), period 2 (therapy with fosinopril) and period 3 (therapy with enalapril). Dialysis conditions were constant and patients were without signs of catabolic state. Laboratory results were followed on monthly basis and mean values were compared by ANOVA-one way test. Difference between variables between periods was tested using Bonferoni method. RESULTS: There was significant difference between mean serum potassium levels throughout three therapeutic periods (5.88 +/- 0.38 vs. 4.9910.44 vs. 5.46 +/- 0.46mmol/l; p<0.001). Difference was evident even in the first month of fosinopril therapy. The effect can not be explained by dialysis adequacy since Kt/ V was similar throughout three treatment periods (1.18 +/- 0.24 vs. 1.25 +/- 0.21 vs. 1.25 +/- 0.14; p=ns). Systolic blood pressure was regulated even better with fosinopril than with enalapril (187.5 +/- 21.4 mmHg vs. 160.0 +/- 20.0 mmHg; p=0.01) and this effect was prolonged during period 3 (160.0 +/- 26.1mmHg). Hemoglobin values mainly depended on specific anemia therapy and not on particular ACEi drug. CONCLUSION: Fosinopril carries less risk of hyperkalemia in hypertensive hemodialysis patients than enalapril. Although definite conclusion may be drawn after well-designed studies, the results presented in this pilot study suggest that fosinopril may be recommended for hypertensive hemodialysis patients who are at risk to develop inter-dialytic hyperkalemia.

Randomised controlled trial of leflunomide in the treatment of immunoglobulin A nephropathy.

AIM: To investigate the effect of leflunomide for treatment of immunoglobulin A (IgA) nephropathy. METHODS: Sixty IgA nephropathy patients were divided into two groups at random. Patients in the test group received leflunomide and patients in the control group received fosinopril. Clinical data were obtained at weeks 2, 4, 6, 8, 12, 16, 20, 24 and 28. RESULTS: The complete remission rate was 62.1% and the total effectiveness rate was 72.4%. In the leflunomide group, proteinuria significantly decreased from 1.66 +/- 0.42 g to 0.60 +/- 0.68 g (P < 0.05). The efficacy rate of leflunomide compared with fosinopril in treating IgA nephropathy was not statistically different (P > 0.05). Side-effects were mild in both treatment groups. CONCLUSION: These preliminary results are encouraging, but further randomised studies are required before leflunomide can be recommended for the treatment of IgA nephropathy.

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency.

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.

Transient recurrent ascites.

Angiotensin-converting enzyme (ACE) inhibitors are widely used in heart diseases. We describe a case of a young woman treated with fosinopril. She started experiencing abdominal pain, vomiting and diarrhoea with peritoneal signs on physical examination three years after her treatment has been initiated. She presented ascites and signs of ileitis on imaging studies. She even underwent surgery. The diagnosis of ACE inhibitor-induced angiooedema of the small bowel was made after the fourth episode. Fosinopril was stopped and the symptoms never recurred. The case we describe illustrates clinical presentation, radiological findings and difficulty of making an accurate diagnosis in such a patient.

Lithium toxicity after switch from fosinopril to lisinopril.

There is a small body of literature on the interactions between lithium and angiotensin-converting enzyme inhibitors (ACEIs), but little data documenting the differences between these agents in their impact on serum lithium levels. We present the case of a 46-year-old male who sustained a five-fold increase in his serum lithium level after switching from fosinopril to lisinopril, with a peak serum lithium level of 3.4 meq/l. There was also an increase in serum creatinine from 1.1 on fosinopril to 1.4 after switching to lisinopril. The patient was hospitalized, and intravenously hydrated with 0.5 normal saline, with a reduction of the serum lithium level to 0.7 meq/l by 72 h after admission. The hospital course was marked by two episodes of bradycardia, but was otherwise uneventful, and the patient was discharged without any neurological sequelae. This case demonstrates that ACEIs may have differential effects on renal function, and the potential for significant alterations in lithium clearance that may not be clinically evident for several weeks. Lithium-treated patients who have a change in ACEI, especially those who are older or have below average renal function, must have diligent monitoring for the first 4-6 weeks after switching to detect potentially serious changes in serum lithium levels.

Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children?

We evaluated the efficacy, safety, and dose-response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment. The study was a prospective, double-blind, placebo-controlled trial conducted in 78 clinical sites in the United States, Russia, and Israel. There were 4 phases: a screening phase of 10 days maximum, a 4-week dose-response phase, a placebo withdrawal phase of 2 weeks maximum, and a 52-week open-label safety phase. The primary objective of the dose-response phase was to determine whether low (0.1 mg/kg), medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure. During the dose-response phase, all 3 doses were equally effective in lowering systolic blood pressure. During the placebo withdrawal phase, there was an adjusted mean systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg for the fosinopril group, a net withdrawal effect of 3.7 mm Hg (P=0.013). Fosinopril was well tolerated; serious adverse events occurred infrequently and were generally not attributed to fosinopril. Because children appear to be more sensitive to lower doses of fosinopril than adults, starting doses for children should be < or =0.1 mg/kg.

Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.

Vasopeptidase inhibitors simultaneously inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of this study was to determine the cardiorenal effects of the vasopeptidase inhibitor omapatrilat in the transgenic m(Ren-2)27 rat which exhibits fulminant hypertension and severe organ pathology. At 6 weeks of age, male Ren-2 rats were randomized to receive no treatment (N = 10), the ACE inhibitor fosinopril 10 mg/kg/day (N = 10), or omapatrilat 10 mg/kg/day (N = 10) or 40 mg/kg/day (N = 10) by daily gavage for 24 weeks. Various cardiorenal functional and structural parameters were assessed. Compared to controls, all treatment groups reduced hypertension in control Ren-2 rats, with both doses of omapatrilat reducing systolic blood pressure significantly more than fosinopril (control, 178 +/- 3 mmHg; fosinopril 10 mg/kg/day, 130 +/- 4 mmHg; omapatrilat 10 mg/kg/day, 110 +/- 3 mmHg; omapatrilat 40 mg/kg/day, 91 +/- 3 mmHg). Omapatrilat dose-dependently reduced cardiac hypertrophy, caused a greater inhibition of renal ACE than fosinopril, and was the only treatment to inhibit renal NEP. Attenuation of albuminuria, glomerulosclerosis and cardiorenal fibrosis occurred to a similar degree with omapatrilat and fosinopril. Omapatrilat confers cardiorenal protection in the hypertensive Ren-2 rat. Although inhibition of tissue NEP may contribute to the superior blood pressure reduction by omapatrilat, overall, the results are consistent with the central role that angiotensin II plays in renal and cardiac fibrosis in this model of hypertension.

Introduction to monitoring. What is what you prescribed actually doing?

BACKGROUND: Having written a prescription for the patient, it is important to monitor for the effects of the drug. OBJECTIVE: This article discusses the importance of patient monitoring as part of the prescribing process, and in particular, what factors to monitor. DISCUSSION: Monitoring of drug therapy is an important part of the prescribing process in enhancing the drug's effectiveness. This is partly due to the large variability in patient response to any given dose of a drug. The drug's effect as well as adverse effects should be actively sought, and dosage alterations made in order to enhance the drug's effect. In some cases, this involves directly monitoring for the drug's effects, and in other cases using surrogate markers.

Ramipril-associated hepatotoxicity.

CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. DESIGN: Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

Acute visual loss after initiation of antihypertensive therapy: case report.

We report the case of a 50-year-old man who reported sudden, painless loss of vision in his left eye after starting antihypertensive therapy. Potential causes of acute painless unilateral visual loss are discussed, as is the initial management of hypertension in asymptomatic patients.

Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.

Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.