The efficacy of low dose metoprolol CR/ZOK in mild hypertension and in elderly patients with mild to moderate hypertension.

In two separate but similarly designed placebo-controlled studies, the efficacy of metoprolol CR/ZOK 50 mg once daily was evaluated in 64 patients (mean age 53 years) with mild hypertension (Study I) and in 34 elderly patients (mean age 68 years) with mild to moderate hypertension (Study II). Both studies were of randomized, double-blind, parallel-group design, the entry criteria for diastolic blood pressure being greater than or equal to 90 less than 105 mm Hg in Study I and greater than or equal to 95 less than 110 mm Hg in Study II. Study I: The impact of metoprolol CR/ZOK 50 mg once daily for 4 weeks compared with placebo 24 hours post dosing was to produce a significant reduction in supine (P = .0001), and standing (P less than .0001) systolic blood pressures and the standing diastolic pressure (P = .035). The supine diastolic pressure was lower after metoprolol CR/ZOK but not significantly so. Study II: Metoprolol CR/ZOK 50 mg daily given to elderly hypertensives when compared with placebo 24 hours post dosing produced a significant fall in supine (P = .022) and standing (P = .022) diastolic pressure. Systolic pressure and heart rate were not significantly reduced. One patient in Study II had a nonfatal myocardial infarct whilst receiving placebo. There were no other serious adverse effects in either study and no patients were withdrawn from the trial because of drug related unwanted events. The studies indicate that 50 mg metoprolol CR/ZOK may be an effective antihypertensive agent which may prove useful in the treatment of mild to moderate hypertension, particularly in the elderly.

Comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia: the Finnish Multicenter Study.

A randomized, double-blind 12-week comparison of lovastatin and gemfibrozil in the treatment of patients with primary hypercholesterolemia with normal or moderately elevated triglycerides was performed in 334 patients from 19 centers in Finland. Patients with "high" total serum cholesterol (240 to 300 mg/dl) constituted Stratum 1 and patients with "very high" total serum cholesterol (greater than 300 mg/dl) constituted Stratum 2. In Stratum 1, patients were randomly assigned to either lovastatin 20 mg nightly or gemfibrozil 600 mg twice daily, and in Stratum 2 to either lovastatin 40 mg nightly or gemfibrozil 600 mg twice daily. In both strata, the lovastatin dose was doubled after 6 weeks if serum cholesterol remained greater than 200 mg/dl. Ninety-two and 93% of the patients doubled their dose in Strata 1 and 2, respectively, resulting in average doses of 38.5 mg/day (Stratum 1) and 77.4 mg/day (Stratum 1) and 77.4 mg/day (Stratum 2) by week 12. The dose of gemifibrozil was kept constant. Lovastatin reduced low-density lipoprotein (LDL) cholesterol by 31 and 42% in Stratum 1 and 2, respectively. The corresponding reductions achieved by gemfibrozil were 13 and 18%. In both strata, as well as in patients with Type IIa and IIb hyperlipoproteinemia, lovastatin was approximately 2 to 4 times as effective as gemfibrozil in lowering LDL cholesterol. Although both drugs increased high-density lipoprotein (HDL) cholesterol concentrations, gemfibrozil was 1.5 to 3 times more effective. LDL/HDL cholesterol ratios decreased significantly more during lovastatin therapy. Both drugs reduced serum triglyceride levels, but gemfibrozil was much more effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Fixed combination of sotalol and hydrochlorothiazide in the treatment of uncomplicated hypertension.

The combination of sotalol and hydrochlorothiazide in a fixed ratio of 6.4:1 was evaluated in thirty patients with uncomplicated hypertension. In the first part of the study, once daily administration of an optimal dose of the combination was significantly more effective than either hydrochlorothiazide or sotalol alone in lowering both the supine and standing systolic and diastolic blood pressure. Blood pressure was still controlled 24 h after the previous dose. Serum potassium fell by 0.37 mEq/l from the mean pretreatment value after treatment with the combination, but it still remained within the normal range. In the second part of the study the long term effect of the combination on blood pressure, heart rate and biochemical parameters was studied in twenty patients. Supine and standing blood pressure fell by 28.7/15.3 mmHg and 29.5/17.6 mmHg, respectively (p less than 0.001). Serum potassium was 3.98 +/- 0.07 mEq/l after twelve months of therapy; potassium supplements were not administered. Like serum potassium, the other biochemical parameters remained within the normal range. The combination was well tolerated on long term use, and only one patient withdrew from the study.

Comparison of guanfacine and clonidine as antihypertensive agents.

1. The antihypertensive effects and side-effects of guanfacine and clonidine were compared in a single-blind, cross-over study. 2. The study consisted of two active treatment periods of 6 weeks each, which were both preceded by a 2 weeks placebo period. Thirty ambulatory, hypertensive patients (blood pressure WHO severity grades I-II) were admitted to the study. The results are based on the 24 patients who completed the study. 3. The optimal daily dose of guanfacine was in over half of the patients 3-4 mg, and of clonidine correspondingly 0.3-0.45 mg. A similar and statistically significant decrease in blood pressure was achieved with both drugs. 4. The most common side-effects with both drugs were tiredness and dryness of the mouth.

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension.

The antihypertensive effect of Inderectic, a new combination capsule of propranolol 80 mg and bendrofluazide 2.5 mg, given twice daily was investigated in 21 hypertensive patients using a double-blind randomized crossover method. Inderectic was compared with either agent used alone and with the same combination given as separate tablets. It gave a greater fall in mean lying and standing systolic and diastolic blood pressure than either agent alone. There was no statistically significant difference for the effect on these variables between the free combination and combined formulation. Only minor side-effects were recorded, no patient having to be withdrawn from the study and no biochemical changes were observed.

Catecholamines in shock.

The role of endogenous catecholamines in various clinical shock and stress states is reviewed; the effects, especially on the peripheral circulation, of catecholamine secretion are the same independent of the cause. Risks of using sympathomimetic agents in the treatment of shock are evaluated. A prolonged noradrenaline activity is to be expected in surgical stress states, e.g. multiple injuries, fat embolism syndrome, burns and infections; therapeutic approaches to minimize the sympathoadrenal activity are outlined.

A controlled study on the anti-hypertensive effect of a new beta-adrenoreceptor-blocking drug, metoprolol, in combination with chlorthalidone.

1. A double-blind cross-over evaluation of the anti-hypertensive effect of metoprolol vs placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving 25 mg of chlorthalidone daily as their basic treatment. An individually determined dose of metoprolol (75-300 mg) was used. 2. Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. 3. During the double-blind cross-over study mild side effects were more common at the beginning of metoprolol/chlorthalidone treatment than during placebo/chlorthalidone, but these tended to diminish or disappear with time. 4. Metoprolol in combination with chlorathalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in patients not responding to chlorthalidone alone.

[Serum enzymes in seriously injured patients]. / Serumenzyme bei Schwerverletzten

In 45 patients with multiple injuries due to trauma, admitted consecutively to our clinic, the following enzyme activities were studied, beginning at the onset of treatment: SDH, GPT, GLDH, and acid phosphatase. The mean levels of SDH rose in all patients between 2 and 24 h after trauma. The mean values of GPT were above normal between 2 and 48 h after trauma; this rise was more pronounced and statistically significant in those patients who eventually died of trauma than in the less severely injured ones. Twenty-four hours after trauma, the levels of GLDH were 16 times higher in the first group of patients than in the less severely injured group. These results lead us to the conclusion that through serum level measurements of these enzymes particularly of GPT it is possible to evaluate the degree of tissue damage and the general state of this group of patients.

A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone.

A double-blind crossover evaluation of the antihypertensive effect of metoprolol v. placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving chlorthalidone (25 mg daily) as their basic treatment. An individually titrated metoprolol dosage (75-300 mg) was used. The double-blind crossover study consisted of two 3-month periods during which the patients received either metoprolol or placebo in addition to chlorthalidone. Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. Normotension was achieved during metoprolol-chlorthalidone treatment in twenty-two of the twenty-three patients, but during placebo-chlorthalidone treatment in only twelve of the twenty-three patients. During the double-blind crossover study mild side-effects occurred during metoprolol-chlorthalidone treatment in fourteen patients during first month, in twelve patients during second month and seven patients during third month. During placebo-chlorthalidone treatment side effects occurred in seven, six and seven patients, respectively. In conclusion, metoprolol caused a significant fall in blood pressure when given to patients already receiving chlorthalidone. Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in those patients not responding to chlorthalidone alone.

Biochemical quantification of blunt injuries.

During eight post-traumatic days, the blood loss and severity of trauma were correlated with the blood levels of lactate, creatinine and catecholamines in 45 patients with multiple blunt injuries. During two days these biochemical indicators correlated with the extent of thoracoabdominal, pelvic and cerebral injuries. In the critically injured patients all three parameters were elevated throughout the observation period. No correlations were observed between plasma catecholamines and lower limb injuries, which seems to make the importance of catecholamines for predicting the onset of fat embolism syndrome less useful.

Plasma catecholamines in severely injured patients: a prospective study on 45 patients with multiple injuries.

Plasma catecholamine levels were studied in 45 severely injured patients for 8 days after the trauma. Sixteen of the patients were classified as critically injured and 29 as seriously injured. The total plasma catecholamine values of the whole group immediately after the injury were almost twice as high as the eighth day reference values and remained significantly higher than these values for 6 hours after the trauma. On admission both the plasma adrenaline and noradrenaline levels were elevated. The plasma adrenaline levels on admission correlated with the blood volume replacement which was required within the first 6 hours. The plasma noradrenaline levels in the critically injured group were significantly higher throughout the observation period than in the seriously injured group. A corresponding difference was observed in the plasma adrenaline concentrations only during the first 12 hours. The results showed that strong stimulation of the sympathetic nervous system occurs in severely injured patients. Factors stimulating the sympathetic nervous system apparently included hypovolaemia, tissue hypoxia, acidosis and the pain produced by the trauma and therapeutic measures.