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Biomedical subjects

L Andrén

Publications and source records attributed to L Andrén.

At least 19 recordsLinked to original sources

Dyspnoea, asthma, and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors.

OBJECTIVE: To evaluate the occurrence of asthma and dyspnoea precipitated or worsened by angiotensin converting enzyme inhibitors. DESIGN: Summary of reports of adverse respiratory reaction in relation to treatment with angiotensin converting enzyme inhibitors that were submitted to Swedish Adverse Drug Reactions Advisory Committee and to World Health Organisation's international drug information system until 1992. Sales of angiotensin converting enzyme inhibitors in Sweden were also summarised. SUBJECTS: Patients receiving angiotensin converting enzyme inhibitors who reported adverse respiratory reactions. MAIN OUTCOME MEASURES: Clinical characteristics of adverse reactions of asthma, bronchospasm, and dyspnoea. RESULTS: In Sweden 424 adverse respiratory reactions were reported, of which most (374) were coughing. However, 36 patients had adverse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33 of these cases the indication for treatment with angiotensin converting enzyme inhibitors was hypertension, in only three heart failure. The respiratory symptoms occurred in about half of the patients within the first two weeks of treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea symptoms occurred in conjunction with other symptoms from the airways or skin in 23 out of the 36 cases. In the WHO database there were 318 reports of asthma or bronchospasm, 516 reports of dyspnoea, and 7260 reports of cough in relation to 11 different angiotensin converting enzyme inhibitors. CONCLUSION: Symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment.

Adult↗

Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors.

OBJECTIVE: To evaluate and describe the clinical course of angio-oedema reactions induced by angiotensin converting enzyme inhibitors. DESIGN AND METHODS: All reports of angio-oedema reactions associated with angiotensin converting enzyme inhibitors submitted to Swedish Adverse Reactions Advisory Committee were reviewed and the clinical courses summarised. Numbers of cases judged to be induced by angiotensin converting enzyme inhibitors were related to their annual usage, estimated from total sales of defined daily doses, as well as to the estimated number of new patients. All cases of angio-oedema associated with angiotensin converting enzyme inhibitors reported to the World Health Organisation's international drug information system were also summarised. RESULTS: 36 of the 38 reported cases in Sweden between 1981 and 1990 were judged to be related to angiotensin converting enzyme inhibitors. During 1981 through 1990, altogether 1309 cases of angio-oedema associated with angiotensin converting enzyme inhibitors were registered with the international drug information system. The incidence of reported cases of angio-oedema increased largely in parallel with the increased sales (usage) of angiotensin converting enzyme inhibitors. Of the 36 Swedish patients, 77% experienced the reaction within the first three weeks after starting treatment. 10 patients needed hospitalisation, two of whom had life threatening laryngeal obstruction. With one exception all 36 patients were free of symptoms within one week after discontinuing the drug. CONCLUSIONS: Angio-oedema induced by angiotensin converting enzyme inhibitors is a rare but potentially life threatening reaction, which in most instances occurs shortly after the start of treatment. Any patient in whom the reaction is suspected should have the treatment interrupted and, if necessary, be admitted for observation.

Adult↗

General considerations in selecting antihypertensive agents in patients with type II diabetes mellitus and hypertension.

The Working Group on Hypertension in Diabetes recommends starting pharmacologic treatment of hypertension with a small dose of a thiazide, beta-blocker, prazosin hydrochloride, angiotensin-converting enzyme inhibitor, or calcium channel blocker. Thus, these alternatives are regarded as first-line treatment in hypertensive patients with diabetes mellitus. Both thiazides and beta-blockers can cause deterioration in glycemic control and have an unfavorable influence on the lipoprotein profile. These metabolic side effects may partly counteract beneficial effects. Non-selective beta-blockers should probably be avoided in diabetic patients, since blockade of the beta-2 receptor may be associated with a compromise in peripheral blood flow and with problems associated with hypoglycemia. Cardioselective beta-blockers, which may have primary preventive effects on coronary disease, are beneficial in this patient group. In patients with non-insulin-dependent diabetes mellitus without nephropathy or overt fluid retention, diuretic therapy could be replaced by sodium restriction and/or calcium channel blocker therapy, since these agents also have a mild diuretic effect. Calcium channel blockers, angiotensin-converting enzyme inhibitors, and prazosin hydrochloride have minimal metabolic side effects, making them suitable for treatment of hypertension in this patient group.

Antihypertensive Agents↗

Diltiazem in hypertensive patients with type II diabetes mellitus.

Twenty-three patients with essential hypertension and diabetes mellitus type II were treated with the calcium antagonist diltiazem (120 to 180 mg twice daily). The mean dose was 307 mg/day. The study was a double-blind, placebo-controlled, crossover design. All measurements were performed 12 to 14 hours after drug intake. Blood pressure, heart rate and forearm blood flow were measured noninvasively. Platelet function was studied by measuring adenosine diphosphate-induced platelet aggregation and the platelet specific proteins, beta thromboglobulin and platelet factor 4. Thromboxane B2 formation in serum and the plasma concentration of diltiazem and its metabolites N-demethyldiltiazem, deacetyldiltiazem and N-demethyldeacetyldiltiazem were measured both during placebo and diltiazem treatment. Diabetic control was evaluated by following HbA1C, fasting blood glucose and urinary glucose. Diltiazem reduced both systolic and diastolic (supine and standing) blood pressure significantly. Forearm blood flow was significantly increased by 32%, p less than 0.05. Supine heart rate decreased significantly, while no such change was seen in the standing position. No significant changes were observed in platelet function during diltiazem treatment. There was no relation between the observed blood pressure reduction and the plasma concentration of diltiazem or its metabolites. A positive correlation between the change in heart rate and the metabolite N-demethyldeacetyldiltiazem was observed (r = 0.647, p = 0.005). Three patients were excluded during diltiazem treatment (skin exanthema, headache and atrial fibrillation) and 1 during placebo treatment (angina pectoris). No negative effect on diabetes control was observed. Thus, diltiazem could be used for treatment of hypertension in diabetic patients.

Adult↗

Hemodynamic effects of loud noise before and after central sympathetic nervous stimulation.

The hemodynamic effects of loud noise after central alpha 2-adrenoceptor stimulation were studied in 13 patients with mild (WHO 1) essential hypertension. The patients were randomized (double-blind) to treatment with either placebo or guanfacine 1-2 mg for four weeks and then crossed over and treated for another four weeks. All patients were exposed to a loud broad-band noise (105 dBA for 30 min) and all were studied both on placebo and guanfacine. Guanfacine significantly reduced the resting blood pressure from 141/92 to 134/88 mmHg (p less than 0.01) as well as heart rate at rest from 63 to 58 beats/min (p less than 0.05). Noise stimulation caused a significant increase in blood pressure and resistance in the placebo-treated group, while cardiac output decreased significantly. Pretreatment for one month with the central alpha 2-adrenoceptor stimulating agent guanfacine did not block the noise-induced pressor response nor the increase in peripheral resistance. A significant decrease in stroke volume was observed and cardiac output also tended to decrease in this group. It could be concluded that loud noise is a potent pressor stimulus which causes vasoconstriction and that the blood pressure response during noise could not be blocked by the centrally acting antihypertensive agent guanfacine. Since noise causes vasoconstriction it also induces an increased tone in the small arteries and, if the noise stimulus is sufficiently strong and repeated for a long time, it might cause structural changes in the resistance vessels and permanent arterial hypertension in humans.

Adrenergic alpha-Agonists↗

Acute and long-term hemodynamic effects of carvedilol, a combined beta-adrenoceptor blocking and precapillary vasodilating agent, in hypertensive patients.

The purpose of these studies was to investigate the hemodynamic effects of carvedilol, a compound with combined properties of nonselective beta-adrenoceptor blockade and precapillary vasodilatation. The acute effects were studied with invasive technique (dye dilution) in 10 patients taking 25 mg orally and noninvasively (forearm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressure (p less than 0.05-0.001) were observed in all groups. Total peripheral resistance (TPR) did not change acutely whereas resistance in the forearm was reduced by 16% (p less than 0.05; invasive group). When a comparison with propranolol (80 mg x 2) was made in a randomized double-blind placebo controlled trial in 30 patients, carvedilol acutely reduced blood pressure significantly by 13/6 mg Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the forearm fell significantly with 50 mg carvedilol, whereas propranolol caused a significant rise. After 4 weeks, both compounds had reduced blood pressure significantly. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. In conclusion, the summary of these studies shows that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment, and it has an attractive hemodynamic profile, in agreement with the hemodynamic findings in essential hypertension.

Adrenergic beta-Antagonists↗

Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.

Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.

Adult↗

The long-term effect of isradipine in pindolol-treated patients.

The long-term efficacy of isradipine, a new dihydropyridine calcium antagonist with marked vascular selectivity, was evaluated in 17 patients with essential hypertension. All had a supine diastolic blood pressure of greater than 95 mmHg with 10 mg pindolol once daily. After a short-term, double-blind, dose-finding, crossover comparison with addition of isradipine or placebo twice daily, they continued on pindolol and their optimal dose of isradipine in a single-blind, long-term follow-up study. Eighteen patients were recruited but one male patient discontinued treatment after 2 weeks due to ankle oedema and will not be accounted for in the overall evaluation. There were 11 males and six females with a mean age of 56 +/- 10 years. In the short-term study on the optimal dose of isradipine (5.1 mg twice daily) blood pressure was lowered by 24/18 mmHg (P less than 0.001). No change in heart rate was seen despite the substantial drop in blood pressure. In the long-term study the patients were seen for a mean follow-up time of 12.5 months (range 4-17 months). After the longest follow-up time mean arterial pressure was 107.0 +/- 7.4 compared with 120.1 +/- 8.2 mmHg after placebo baseline [delta = 13 mmHg (11%), P less than 0.001, n = 17]. The heart rate was unchanged (delta = 0.2 beats/min, 95% confidence limits -3, +3), and so was ankle circumference (delta = 0.12 cm, 95% confidence interval, -1, +1). On the other hand, mean weight was reduced by 2 kg from 90 kg (P less than 0.05, n = 17).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term effects of captopril and atenolol in essential hypertension.

Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n = 26) or atenolol (n = 24). Their mean supine diastolic blood pressure after placebo was 100-125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure less than 95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p less than 0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p less than 0.01 (systolic), p less than 0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.

Adult↗

Hemodynamic effects of combined beta-adrenoceptor blockade and precapillary vasodilatation in hypertension.

Carvedilol (BM14190) is a new compound with combined properties of nonselective beta-adrenoceptor blockade, devoid of ISA, and precapillary vasodilatation. Its acute hemodynamic effects were studied with invasive technique (dye-dilution using Cardio-Green) in 10 patients taking 25 mg orally and noninvasive (fore-arm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressures (p less than 0.05 - 0.001) were observed in all groups. TPR did not change acutely whereas resistance in the fore-arm was reduced by 16% (p less than 0.05). When a comparison with propranolol (80 mgx2) was made in a randomized, double-blind placebo controlled trial comprising 30 patients with essential hypertension, carvedilol acutely reduced blood pressure significantly 13/6 mm Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the fore-arm (plethysmography) fell significantly with carvedilol 50 mg whereas propranolol caused a significant rise. After 4 weeks both compounds had reduced blood pressure significantly and to the same extent. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. We conclude that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment. It has an attractive hemodynamic profile.

Adrenergic beta-Antagonists↗

Potentiation of the antihypertensive effect of enalapril by randomized addition of different doses of hydrochlorothiazide.

The purpose of this study was to evaluate the potentiating effect of hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily when added in a placebo-controlled double-blind randomized study of patients with essential hypertension, whose diastolic blood pressure (DBP) was not adequately controlled (DBP > 90 mmHg) following 6 weeks of single-blind treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril, 20 mg once daily. Forty-eight patients started the first period with enalapril after 4 weeks on placebo. In 13 patients DBP fell to < or = 90 mmHg after enalapril for 6 weeks. In this group supine mean arterial pressure (MAP) was reduced by 13% (P < 0.01). In the patients whose DBP was > 90 mmHg after 6 weeks on enalapril (n = 32) the average supine MAP fell by 9% (P < 0.001). After 3 weeks there was no further drop in blood pressure (BP). Addition of HCTZ to the 32 patients with DBP > 90 mmHg caused a significant further drop in supine BP by 13/7 mmHg with 12.5 mg and by 15/7 mmHg with 25 mg. Seven patients discontinued the study, none due to side effects on enalapril alone. Well-being, assessed with a special questionnaire, was significantly better with enalapril as monotherapy compared with previous treatment, but not different from well-being during the placebo periods. It is concluded that 20 mg enalapril once daily lowered BP effectively and was well tolerated. The maximum BP lowering effect was seen within 3 weeks. Addition of HCTZ caused a significant, and clinically relevant, further drop in BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Haemodynamic effects of loud noise in hypertensive patients treated with combined beta-adrenoceptor blockade and precapillary vasodilatation.

The effects of acute exposure to noise on central and regional (calf and forearm) haemodynamics were studied during placebo therapy and during combined nonselective beta-adrenoceptor blockade and precapillary vasodilatation in 9 patients with essential hypertension. On placebo therapy a loud noise (105 dBA for 10 min) caused a significant increase in diastolic and mean arterial pressure due to vasoconstriction. There was also a significant increase of vascular resistance in the calf. After combined precapillary vasodilatation and non-selective beta-adrenoceptor blockade, the increase in blood pressure during stimulation with noise was not prevented. Thus, systolic as well as diastolic and mean arterial pressures increased significantly. This indicates a temporary resetting of the baroreceptors, allowing a higher level of blood pressure during stimulation with noise. Such a resetting would involve the central nervous system pathways of the baroreflex and this would explain why the peripherally active therapeutic principle--precapillary vasodilatation and beta-adrenoceptor blockade--was unable to inhibit the blood pressure response induced by noise.

Adult↗

Haemodynamic effects of carvedilol, a new beta-adrenoceptor blocker and precapillary vasodilator in essential hypertension.

Carvedilol (BM 14190) is a new antihypertensive compound which combines beta-adrenoceptor blocking and precapillary vasodilating properties but is devoid of intrinsic sympathomimetic activity. The acute and long-term effects on blood pressure and regional haemodynamics (forearm plethysmography) were studied with carvedilol 25 mg b.i.d. or 50 mg b.i.d. Comparisons were made with propranolol 80 mg b.i.d. in a randomized double-blind placebo controlled trial comprised of 30 patients with essential hypertension. After a four-week placebo period active therapy was given for four weeks. Carvedilol administered acutely reduced blood pressure at both doses, delta 13/6 mmHg (P less than 0.001/P less than 0.01) and 17/10 mmHg (P less than 0.001/P less than 0.01). Resistance in the forearm fell significantly with the higher dose. This was in contrast to propranolol which only reduced heart rate acutely, and as expected caused a rise in forearm resistance. After four weeks both compounds had reduced blood pressure significantly and to the same extent. Blood flow was still significantly reduced with propranolol in contrast to the findings with carvedilol. We conclude that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment. It is well tolerated and its haemodynamic profile is attractive.

Adrenergic beta-Antagonists↗

Arthrography of the dislocated elbow joint.

Arthrography has been suggested as a useful tool for diagnosing ligament ruptures. In 14 consecutive patients with non-fractured elbow dislocations arthrography was performed after reduction of the dislocation. One or two days following arthrography all elbows were examined under general anesthesia with regard to stability and half of them were randomized for surgery with exploration and suture of both the ulnar and the radial collateral ligaments. Arthrography, even if performed within 24 hours after the injury, was found to be unreliable in diagnosing ligament injuries after elbow dislocation. Leakage of the contrast medium was more or less limited to the site of the major injury, which in the dorsal and dorso-radial dislocation was a rupture of the volar aspect of the capsule and the ulnar side of the joint in the radial dislocation.

Adolescent↗

Acute haemodynamic effects of carvedilol (BM 14190), a new combined beta-adrenoceptor blocker and precapillary vasodilating agent, in hypertensive patients.

Carvedilol (BM 14190) is a new compound with combined nonselective beta-adrenoceptor blocking activity, devoid of ISA, and a precapillary vasodilating effect. Its acute haemodynamic effects were studied by invasive techniques in 10 patients given 25 mg carvedilol and noninvasively in 10 patients given 25 mg and in 10 given 50 mg orally. All had essential hypertension. In the invasive study intraarterial blood pressure was measured and cardiac output was determined by the dye-dilution method using Cardio-Green as the indicator. Peripheral haemodynamics in all 30 patients were studied in the forearm using strain gauge plethysmography. Measurements were made at rest before and repeatedly for 90 minutes after oral administration of one capsule of 25 mg or 50 mg carvedilol. Significant reductions in the systolic and diastolic blood pressures (p less than 0.05-0.001) were observed in all groups. Cardiac output showed a small, non-significant decrease from 5.81/min to 5.1 l/min. Total peripheral resistance did not change, whereas resistance in the forearm fell by 16% (p less than 0.05). These findings are different from what would have been expected acutely after administration of a pure beta-adrenoceptor blocking agent. They indicate that carvedilol possesses vasodilating activity in addition to its beta-adrenoceptor blocking effect.

Adrenergic beta-Antagonists↗