[Systematic review and sequential analysis of Tanshinone â ¡_A Sodium Sulfonate Injection combined with enalapril in treatment of acute exacerbation of pulmonary heart disease].

To systematically evaluate the clinical efficacy and safety of Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril in the treatment of patients with acute exacerbation of pulmonary heart disease. The randomized controlled trial(RCT) on Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril for acute exacerbation of pulmonary heart disease was screened from EMbase, PubMed, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang from inception to March 20, 2022. Meta-analysis of each index was performed in RevMan 5.3 and TSA 0.9. Finally, 41 RCTs involving 3 865 patients were included. Meta-analysis showed that the observation group had higher total response rate(RR=1.21, 95%CI[1.18, 1.24], P<0.000 01), lower plasma viscosity(MD=-0.25, 95%CI[-0.34,-0.16], P<0.000 01), lower whole blood viscosity(MD=-0.99, 95%CI[-1.14,-0.85], P<0.000 01), and lower hematokrit(MD=-9.03, 95%CI[-10.57,-7.50], P<0.000 01) than the control group. The incidence of adverse effects showed no significant difference between groups(RR=1.42, 95%CI[0.82, 2.45], P=0.21). Sequential analysis showed that Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril exerted definite efficacy in the treatment of acute exacerbation of pulmonary heart disease, and the possibility of false positives was excluded. Based on the existing evidence, Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril can improve the total response rate and reduce plasma viscosity, whole blood viscosity, and hematocrit, demonstrating good safety in patients with acute exacerbation of pulmonary heart disease. In the future, more RCT with large sample size, rigorous design, and in accordance with international norms are needed to further validate the results.

The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT.

OBJECTIVE: In a subgroup analysis of the China Stroke Primary Prevention Trial, we aimed to explore the impact of folic acid supplementation on arterial stiffness and assess the modifying effect of the methylenetetrahydrofolate reductase (MTHFR) gene in Chinese patients with hypertension. METHODS: This prospective study enrolled 2529 hypertensive Chinese patients. Participants were randomized to receive treatment with either a combination of enalapril and folic acid or enalapril. Brachial-ankle pulse wave velocity (PWV) was measured by trained medical staff using PWV instruments at both baseline and exit visits, approximately 5 years after enrollment. This trial was registered with clinicaltrials.gov (NCT00794885). RESULTS: During the follow-up, change in folate was significantly and independently correlated with change in ba-PWV in study patients (ß = -1.31, P < 0.001). Individuals with CC genotype had a significantly greater PWV response to folic acid supplementation than did carriers of the T allele (ß = -2.79, P < 0.001 for CC homozygotes compared with ß = -0.56, P = 0.464 for TT homozygotes). The positive effect of folic acid on improved PWV was modified by the MTHFR genotype (P for interaction = 0.034). CONCLUSION: In a subgroup of Chinese hypertensive patients who had received 5-year antihypertensive therapy, increases in folate status were associated with higher reductions in PWV, and individuals with the CC genotype showed greatest PWV response to folic acid supplementation.

Herbal and dietary supplements related to diarrhea and acute kidney injury: a case report.

Background There is very little evidence relating to the association of herbal medicine with diarrhea and the development of acute kidney injury (AKI). This study reports a case of diarrhea-induced AKI, possibly related to an individual ingesting copious amounts of homemade mixed fruit and herb puree. Case presentation A 45-year-old Thai man with diabetes had diarrhea for 2 days, as a result of taking high amounts of a puree made up of eight mixed fruits and herbs over a 3-day period. He developed dehydration and stage 2 AKI, with a doubling of his serum creatinine. He had been receiving enalapril, as a prescribed medication, over one year. After he stopped taking both the puree and enalapril, and received fluid replacement therapy, within a week his serum creatinine had gradually decreased. The combination of puree, enalapril and AKI may also have induced hyperkalemia in this patient. Furthermore, the patient developed hyperphosphatemia due to his worsening kidney function, exacerbated by regularly taking some dietary supplements containing high levels of phosphate. His serum levels of potassium and phosphate returned to normal within a week, once the patient stopped both the puree and all dietary supplements, and had begun receiving treatment for hyperkalemia. Results The mixed fruit and herb puree taken by this man may have led to his diarrhea due to its effect; particularly if the patient was taking a high concentration of such a drink. Both the puree and enalapril are likely to attenuate the progression of kidney function. The causal relationship between the puree and AKI was probable (5 scores) assessed by the modified Naranjo algorithm. This is the first case report, as far as the authors are aware, relating the drinking of a mixed fruit and herbal puree to diarrhea and AKI in a patient with diabetes. Conclusions This case can alert health care providers to the possibility that herbal medicine could induce diarrhea and develop acute kidney injury.

Mancha hiperpigmentada muy pruriginosa en la espalda / Highly pigmented stain on the back

No disponible

Rationale for the use of a fixed-dose combination in the management of hypertension: efficacy and tolerability of lercanidipine/enalapril.

Hypertension, a significant factor in the development of cerebrovascular disorders, heart disease and renal failure, is a common disorder worldwide. Despite the availability of a wide range of antihypertensive agents, almost two-thirds of hypertensive patients have poorly controlled blood pressure (BP). Numerous clinical trials have shown that most patients require at least two antihypertensive agents to achieve adequate BP control and associated significant reductions in cardiovascular morbidity and mortality. Combination therapy using two drugs with different, complementary mechanisms of action achieves better efficacy and tolerability outcomes than treatment with either component drug alone. When such a combination is administered as a fixed-dose formulation, other benefits, such as improved compliance and potentially lower costs, are also likely. The good efficacy and tolerability of the combination of a calcium channel antagonist and an angiotensin-converting enzyme inhibitor is well established, and this combination is recommended by European Society of Hypertension/European Society of Cardiology guidelines as a first choice in high-risk hypertensive patients, including those with type 2 diabetes mellitus. Lercanidipine/enalapril is a promising example of a fixed-dose combination of these drug classes. In clinical trials in hypertensive patients, including those with type 2 diabetes, lercanidipine/enalapril improved BP to a greater extent than either drug as monotherapy (in patients who were previous non-responders to lercanidipine or enalapril) or the combination of lercanidipine/hydrochlorothiazide, and was equally well tolerated. Further studies are required to evaluate the cardiovascular protective effects of lercanidipine/enalapril.

The role of fixed-dose combinations in the management of hypertension: focus on lercanidipine-enalapril.

Achieving optimal blood pressure (BP) control is the most important single issue in the management of hypertension, and in most patients, it is difficult or impossible to achieve target levels with one drug. Blocking two or more regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed-dose combination therapy is an efficacious, relatively safe and cost-effective treatment option in most patients with essential hypertension. Of note, the once-daily administration of a fixed-dose enalapril/lercanidipine, by bringing together two distinct and complementary mechanisms of action, reduces BP effectively and has the potential for improved target organ protection relative to either class agent alone.

Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

BACKGROUND AND OBJECTIVE: Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. METHODS: This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of > or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. RESULTS: Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (+/- SD) decreases of 26.5 (+/- 14.4) mmHg and 14.9 (+/- 9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n = 689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product. CONCLUSIONS: The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.

Investigando enfermedades raras del adulto en atención primaria: una hipótesis clasificatoria / Rare diseases at a primary care facility

Las enfermedades raras (ER) han de ser un objetivo de investigación en atención primaria por su potencial de productividad científico-biológica. Nos parece necesaria una sistematización de los resultados. Hemos realizado este trabajo retrospectivo longitudinal que recoge los hallazgos más importantes de nuestro interés en las ER de base genética. Los resultados se han clasificado en: a) observación y comunicación de reacciones adversas a medicamentos raras (RAMR); b) diagnóstico de entidades nosológicas raras (ENR); y c) estudio de prevalencia de ER (PER)

A pragmatic classification. Rare diseases (RD) might be a research target on primary care because their gift of scientific knowledge building. A rational scheme would be necessary for clinical and scientific findings. Retrospective long-term report of the most important RD achieved for a ten years period by a general practitioner at a non-urban primary care facility (Andalusia-Spain). Our results are classified as: a) rare adverse drug reactions (RADR); b) accurate RD diagnosis (RDD); and c) RD prevalence study (RDP)

Pseudoaldosteronism due to the concurrent use of two herbal medicines containing glycyrrhizin: interaction of glycyrrhizin with angiotensin-converting enzyme inhibitor.

A 77-year-old man with a history of hypertension and hyperuricemia was admitted to our hospital complaining of limb weakness, persistent constipation, and worsening hypertension. He had been taking a Chinese herbal remedy for allergic rhinitis for the past 10 years, together with an angiotensin-converting enzyme inhibitor (ACE-I; enalapril, 20 mg daily). After the dosage of enalapril had been reduced to 10 mg daily about 1(1/2) years before the current admission, he had developed persistent constipation. Therefore, he had started taking another traditional Chinese herbal remedy, a laxative, for the constipation, about 4 months prior to this hospitalization. Laboratory data on admission demonstrated marked metabolic alkalosis with severe hypokalemia associated with urinary wasting of potassium and chloride. A diagnosis of pseudoaldosteronism was made based upon his past history of exposure to various traditional Chinese medicines containing glycyrrhizin. Discontinuation of the Chinese remedies and supplementation of potassium successfully normalized the electrolyte imbalance and relieved all symptoms within a short time. The present case describes the occurrence of pseudoaldosteronism induced by a patient taking two traditional Chinese herbs, both containing glycyrrhizin, resulting in an overdose of this causative chemical agent. The development of pseudoaldosteronism appeared to be of particular interest with regard to the interaction of the renin-angiotensin-aldosterone (RAA) system with glycyrrhizin, in which an ACE-I retarded the development of pseudoaldosteronism.

Factors related to the occurrence of microalbuminuria during antihypertensive treatment in essential hypertension.

The objective of the study was to assess the factors related to the occurrence of microalbuminuria during the follow-up of a young adult group with essential hypertension that had not been previously treated. Normo-albuminuric essential hypertensives, <50 years old, who had not been previously treated with antihypertensive drugs and who did not have diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=62), beta-blockers (n=38), ACE inhibitors (n=64), calcium channel blockers (n=8), and several classes (n=15). Measurements were taken for office blood pressure, biochemical profile, and 24-hour urinary albumin excretion at the beginning of the study and were measured yearly during an average of 2.7+/-1.2 years of follow-up. Among the 187 patients included, 22 (11,7%) developed microalbuminuria (progressors, 4.4/100 patients/y). No differences were present between progressors and those who remained normo-albuminuric (nonprogressors) in terms of age, gender, body mass index, disease duration, blood pressure values, biochemical profile, familial history of diabetes or hypertension, smoking habits, or the presence of EKG left ventricular hypertrophy. The group with the lowest progression rate was the patients treated with ACE inhibitors (n=5; 2.9/100 patients/y), followed by the diet group (n=5; 3.3/100 patients/y) and the beta-blockers group (n=5; 4.1/100 patients/y). When we excluded patients treated with calcium channel blockers or those who changed over time between different classes of treatment, no significant differences in the incidence of microalbuminuria were observed among the groups. Progressors showed higher slopes of fasting glucose (4.78+/-11.4 versus 0.50+/-6.8 mg/y, P<0.02) and uric acid (0.58+/-0.93 versus 0.05+/-1.10 mg/y, P<0.03) compared with the slopes of nonprogressors. Both the slopes for glucose and systolic blood pressure over time were associated independently with the slope of the logarithm of urinary albumin excretion when adjusted for age, gender, and treatment groups. Cox proportional hazard model for progression of microalbuminuria showed that baseline urinary albumin excretion (risk ratio [RR]=1.06; confidence interval [CI] 95%, 1.01 to 1.11), slope for systolic blood pressure (RR=1.11; CI 95%, 1.03 to 1.20), and slope for glucose (RR=1.08; CI 95%, 1.03 to 1.14) were independently associated to the development of microalbuminuria. In conclusion, in a group of young adults with essential hypertension that had not been previously treated, the main factors influencing the occurrence of microalbuminuria during antihypertensive treatment were the values of microalbuminuria at baseline and the slopes for systolic blood pressure and fasting glucose.

Nitrendipine and enalapril combination therapy in mild to moderate hypertension: assessment of dose-response relationship by a clinical trial of factorial design.

Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality. Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required. As many as 50% of patients require the addition of a second agent to achieve satisfactory blood pressure control. The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension. A total of 496 patients were enrolled in a multicenter, randomized, double-blind, factorial-design, parallel-group clinical trial comparing placebo, nitrendipine (5, 10, and 20 mg) and enalapril (5, 10, and 20 mg) alone or in combination. After a single-blind, 2-week placebo run-in period, 414 patients whose diastolic blood pressure ranged between 90-109 mm Hg were randomly assigned to a treatment group. The combination of nitrendipine and enalapril, particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg, were significantly superior to both monotherapies; mean diastolic blood pressure reductions from baseline to last visit were -12.5 and -14.3 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy. All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups. In summary, the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses. The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg.

[Activation of bradykinin formation cascade on receiving autologous blood transfusion through a white cell-reduction filter in a patient treated with an ACE inhibitor].

We have experienced a case of anaphylactoid reaction on receiving autologous blood transfusion through a WBC filter for packed red blood cell (PRBC). The patient was a 71-year-old man with a history of hypertension treated with oral antihypertensive drug; enalapril, an angiotensin converting enzyme (ACE) inhibitor, who received anesthesia for Y-graft replacement. Autologous blood was obtained after the induction of general anesthesia in the operating room. Upon starting to return the stored blood with an unintentional use of a WBC filter, arterial blood pressure (ABP) fell within the first minute of the transfusion. We obtained three blood samples; pre-filtered blood (PRE), postfiltered blood (POST) and arterial blood (CIRC) after the event, and analyzed concentrations of bradykinin (BK), high molecular weight kininogen (HMWK) and high molecular weight kininogen-light chain (HMWK-LC). BK was higher in POST than in PRE. HMWK was lower in POST than in PRE, while HMWK-LC was higher in POST than in PRE. HMWK in CIRC was lower than in PRE, and HMWK-LC was higher in CIRC than in PRE. HMWK and HMWK-LC changes after the event suggest that BK formation cascade in the patient was activated on receiving the transfusion. ACE inhibitors were reported to augment such activation. The WBC filter has the negatively charged surface on filteration material and may activate the cascade. While WBC filters can avoid transfusion related reactions, hemodynamic responses should be watched closely in patients treated with ACE inhibitors.

The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.

BACKGROUND: It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study. METHODS: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes. The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes. In the current study, we analyzed data on a secondary end point (the incidence of myocardial infarction) in the subgroup of patients in the ABCD Trial who had hypertension. RESULTS: Analysis of the 470 patients in the trial who had hypertension (base-line diastolic blood pressure, > or = 90 mm Hg) showed similar control of blood pressure, blood glucose and lipid concentrations, and smoking behavior in the nisoldipine group (237 patients) and the enalapril group (233 patients) throughout five years of follow-up. Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8). CONCLUSIONS: In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril. Since our findings are based on a secondary end point, they will require confirmation.

Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.

Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect.

Tamsulosin, an alpha 1A-adrenoceptor antagonist, has recently been approved to treat patients with symptomatic benign prostatic hyperplasia (BPH). Tamsulosin is highly selective for prostatic receptors with minimal affinity for vascular receptors. Therefore, it should have little effect on blood pressure and should not potentiate other agents' antihypertensive activity. To test this hypothesis, we conducted three randomized, double-masked, placebo-controlled studies to evaluate how coadministration of tamsulosin would affect the pharmacodynamic profiles of nifedipine, enalapril, and atenolol. Each study enrolled 12 hypertensive men aged 45 years or older whose blood pressure was being controlled with maintenance doses of nifedipine (study 1), enalapril (study 2), or atenolol (study 3). All 36 subjects were treated with placebo for 5 days and then randomly assigned to either placebo (control group) or tamsulosin therapy (0.4 mg/d for 7 days followed by 0.8 mg/d for 7 days) in addition to continuing their maintenance antihypertensive therapy. Blood pressure and pulse rate were monitored over a 24-hour period on study days 4, 11, and 19. Coadministration of tamsulosin in these small studies had no clinically significant effects on the pharmacodynamic action of nifedipine, enalapril, or atenolol; it produced no clinically significant differences in pulse rate and blood pressure, did not alter electrocardiographic or Holter monitoring results, and did not cause increased side effects. Coadministration of tamsulosin with the three antihypertensive agents studied had a favorable safety profile. Our results in these small studies indicate that the dose of nifedipine, enalapril, or atenolol did not require adjustment in patients given tamsulosin, which may give tamsulosin an advantage over other alpha-blocking agents used to treat patients with BPH. Now that tamsulosin has been approved in the United States, further clinical use may confirm these findings.

Angiotensin-converting enzyme inhibitor-induced angioedema: late onset, irregular course, and potential role of triggers.

Angioedema is a rare but potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACEI) which usually occurs within the first weeks of therapy. We report three patients in whom ACEI-induced angioedema began with a late onset of 12-33 months, and who had an irregular, unpredictable course under ACEI therapy. In two patients, other drugs or trauma appeared to trigger some of the episodes. After withdrawal of the ACEI, the trigger drugs were well tolerated in provocation tests and upon re-exposure. To avoid putting some patients unnecessarily at risk for long periods, one should consider this irregular pattern of ACEI-induced angioedema and regularly monitor patients for this adverse effect.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs.

A 40-year-old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L-1) during high dose treatment with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride-like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, and the combination of ACE-inhibition and potassium-sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE-inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE-inhibitors with other potassium-sparing diuretics.

Nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria.

A trial to study the efficacy, safety and tolerability of nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria (MA) was performed to compare the effects of both drugs in the prevention of the renal impairment. Twenty-eight valid patients [13 with nitrendipine (N) and 15 with enalapril (E) with NIDDM, hypertension (diastolic blood pressure between 90 to 114 mm Hg) and MA (urinary albumin between 30 to 300 mg/24 hr) were recruited in a double blind, randomized trial. Following a placebo run-in period of two to four weeks, all eligible patients were randomly allocated to either N or E treatment. Treatment lasted six months, with two different visits at three and six months in which blood pressure (BP), heart rate (HR), renal function and MA were measured. No statistically significant differences on BP and metabolic parameters were found between both treatment groups. The geometric mean of final glomerular filtration rate (GFR) in the N group was 34.5% higher than in the E group, while the reduction on MA was most important in the E group. Eleven patients reported adverse events (AEs) and there were four dropouts, three of them due to AEs. We conclude that both treatments are a good choice for treating diabetic hypertensive patients with early altered renal function, as they reduce BP without altering metabolic parameters, increase GFR and reduce MA with a low frequency of AEs.