[Interactions of hypotensive agents]. / Interakcje leków hipotensyjnych.

Drug interactions are an important and often under-appreciated cause of adverse clinical outcomes. They are classified as pharmacokinetic, pharmacodynamic, or both. Pharmacokinetic interactions occur when one drug modifies the other drug's absorption, distribution, metabolism, or excretion. Recently, several scientific advances, particulary in cytochrome P-450 drug-metabolizing enzymes, have revolutionized the study of drug interactions. This review considers the metabolic mechanisms for several clinically important drug interactions that involve major classes of hypotensive agents. Although it is not possible for an individual health practitioner to recognize all clinically important drug interactions, it is possible to understand the important scientific principles that pertain to this topic.

[Effect of one-year treatment with low simvastatin doses on lipids and Lp(a) in patients with significant hypercholesterolemia]. / Wplyw rocznego leczenia niewielkimi dawkami simwastatyny na lipidogram i Lp(a) u chorych z nasilona hipercholesterolemia.

The aim of study was to evaluate efficacy and safety of one-year therapy with simvastatin in relative low doses (5-20 mg/d). The examination was performed in the group of 55 patients with significant hypercholesterolemia (Fredrickson's type II). During one-year treatment with simvastatin there were observed the mean decrease of total cholesterol (TC) by 26%, LDL-C by 37%, and LDL-C/HDL-C rate by 38%. The normalization of cholesterolemia (TC < 200 and LDL-C < 130 mg/dL) was observed in 53% of patients (group A-75%, and group B-39%). Effective doses of simvastatin varied from 5 to 20 mg/d. Lp(a) decreased statistically significantly only in the group of patients with extensively elevated Lp(a): from 121.1 +/- 46.2 mg/dL before the treatment to 95.3 +/- 31.3 mg/dL after them. Hepatotoxic effects were not observed and antipyrine kinetics did not change during one-year treatment with simvastatin.

Bisoprolol in the treatment of hypertension in the elderly.

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.

Efficacy and safety of one-year treatment with slow-release nicotinic acid. Monitoring of drug concentration in serum.

The paper is aimed at evaluation of the efficacy and safety of one-year therapy with slow-release nicotinic acid (NA-SR). The study involved a group of 30 patients with hyperlipidemia of type II. The concentration of nicotinic acid in serum was determined using capillary electrophoresis. After the placebo period (2 months), NA-SR was applied at the dose of 1.5 g/d (2 months), and subsequently 2-3 g/d (10 months), on average 2.13 g/d. During the treatment with 2.0 g/d dose, the steady-state concentration of NA in serum was within a range of 2.7-4.9 microg/ml and with 3.0 g/d of 6.17-7.75 microg/ml. These doses of the drug were tolerated well and advantageously modified the serum lipids.

[Prolonged treatment with slow release nicotinic acid in patients with type II hyperlipidemia]. / Przewlekla terapia kwasem nikotynowym o powolnym uwalnianiu pacjentów z hiperlipidemia typu II.

The aim of the study was to compare efficacy and safety of one-year therapy with slow-release nicotinic acid (KN-SR) and with ordinary form of the acid (KN). The examination was performed in the group of 136 patients with hyperlipidemia-type II. KN-SR had satisfactory effectiveness and was much better tolerated than KN. During one-year treatment with KN-SR there were observed the decrease of total cholesterol (TC) by 18%, LDL-C by 22%, triglycerides by 36%, Lp(a) by 56%, and the increase of HDL-C by 12%. The percentage of skin unwanted signs differed significantly between KN-group (90.2%) and KN-SR group (24%). Hepatotoxic effects were not observed and antipyrine kinetics did not change during one-year treatment with slow-release nicotinic acid.

[Lovastatin in the treatment of hypercholesterolemia]. / Lowastatyna w leczeniu hipercholesterolemii.

In 9 clinics 177 patients (68 men and 109 women) aged 23-69 years with primary hypercholesterolemia (TC above 6.5 mmol/L) were treated with lovastatin for 12 weeks. The treatment was started with 20 mg daily. The dose was doubled every 4 weeks, if the total serum cholesterol level did not fall below 5.2 mmol/L. For 4 weeks before treatment with lovastatin all patients received placebo. After the first 4 weeks of therapy the mean TC level decreased significantly (from 8.09 mmol/L to 6.54 mmol/L) by 18.5%. In comparison with the results after placebo (the starting value), after the 8 weeks of the therapy the TC level reduction reached 22.4% and after 12 weeks 23.5%. The mean LDL cholesterol decreased by 26.1%, 30.8% and 32.9% after 4.8 and 12 weeks of lovastatin treatment respectively. An increase in HDL cholesterol by 5.9%, 6.0% and 7.6% and decrease in triglyceride level by 10.7%, 14.9% and 14.0% respectively was also observed. In 6 patients on lovastatin treatment symptoms of acute pancreatitis in 1 case, a cataract in 1 case and aggravation of coronary insufficiency in 4 cases were noticed. These symptoms in the light of our knowledge of the mechanism of action of the drug used and of its side effects described in other trials, may be considered of independent on lovastatin. The treatment was discontinued in 5 cases (because of gastrointestinal intolerance in 2 patients, of aggravation of coronary insufficiency in 2 patients and of pain in the right hypochondrium in 1 patient who himself decided to stop the therapy).(ABSTRACT TRUNCATED AT 250 WORDS)

[Monitoring treatment with amikacin for urinary tract infections]. / Monitorowane leczenie amikacyna zakazen dróg moczowych.

The studies were aimed at the determining the serum amikacin levels during the treatment of urinary tract infection as an attempt to monitor this treatment. The study involved 51 patients. Amikacin profile following a single dose of 500 mg i.m. was studied in group 1 (n = 7) while the administration of 2 daily doses of 500 mg for 7 days was investigated in group 2 (24 patients with normal renal functioning). Group 3 (10 patients with renal failure) was given the same amikacin doses for 5 days. Amikacin dosage was modified with the own computer program in group 4. Both lower and peak amikacin serum levels in the groups 1, 2 and 3 ranged markedly from subtherapeutical to toxic. Blood urea and creatinine increased significantly in groups 2 and 3. In group 4 amikacin peak level exceeded in therapeutical value only in out patient, and no an increase in blood creatinine or urea was noted during a 5-day therapy.

[Captopril treatment--2-year period of observation]. / Leczenie kaptoprylem--2-letni okres obserwacji.

Captopril was administered to 50 carefully selected patients with severe circulatory failure (18 patients classified as class III and 32 as class IV according to NYHA) in daily dose of 37.5-75 mg for two years. Patients were also given digoxin, diuretic agents and iso-dinitrosorbide. Clinical improvement increased with duration of captopril therapy. A significant improvement following the correction of therapy was achieved in 15% of patients, following one month in 28%, three months--in 70%, and after 1 and 2 years in 84% of the treated patients. All patients survived for one year, and 44--for two years (88%). Clinical improvement was manifested by: diminished of dyspnoea, edema, pulmonary and liver congestion, increase in left ventricle ejection fraction, change of disease staging by one or two NYHA classes, and reduced ventricular rate during atrial fibrillation (in 30% of patients within one year). More noticeable improvement was seen in patients with baseline ejection fraction > 40% than those with EF < 30%, in hypertensive patients than normotensive, and in patients classified to III NYHA class. Ejection fraction increased from 37.9 +/- 9.2% before the treatment to 54.6 +/- 7.7% after a two-year captopril therapy (p < .01). Captopril greatly contributes to the successful therapy of the chronic severe heart failure.

[Changes in hepatic biotransformation in patients treated with beta-adrenergic drugs and prazosin]. / Zmiany biotransformacji watrobowej u chorych leczonych zwiazkami beta-adrenolitycznymi i prazosyna.

Biotransformation in the liver was tested with antipyrine elimination test in 41 patients treated with prazosin for 3 months (Minipress Pfizer, 1-4 mg a day) or prazosin combined with beta-adrenolytic agents (propranolol 40-80 mg; metoprolol 100-200 mg daily). It was found that T0.5 of antipyrine is shortened in patients treated with prazosin alone by 3 h/p greater than .05/while in the patients treated with prazosin whom previously--adrenalytics were given by 7.5 h/p greater than 0.01/. Antipyrine half-life during the treatment with beta-adrenolytics was prolonged by + 5.3 h/p greater than .05/while during the combined therapy with these agents and prazosin - 3.8 h. These results indicate that prazosin contrary to beta-adrenolytics, does not affect biotransformation in the liver. During combined therapy with prazosin and beta-adrenolytics, unfavourable effect of the latter in prevailing. Replacement of beta-adrenolytics with prazosin may prevent unfavourable effect of the former on liver functioning and may increase the safety of the hypotensive treatment.

[Effectiveness of diet therapy of obesity in women in the climacteric period]. / Skutecznosc dietetycznego leczenia otylosci u kobiet w okresie klimakterium.

Twenty-five women at the climacteric age (mean age 48.5 +/- 5.5 years) were treated for simple obesity (mean overweight 37.8%) giving them low-calorie, low-carbohydrate and low-sodium diet for 14 days. The diet was very well tolerated by the patients. The mean weight loss was 4.4 kg, with 72.7% of this loss in the first week on the diet. A considerable reduction of the activity of dopamine beta-hydroxylase were noted, indicating a decrease of the activity of the adrenergic system. At the same time the diet stimulated thyroid function, as shown by increased concentration of total thyroxine (without exceeding the normal upper range), and higher free thyroxine index. Besides that, the serum uric acid level was increased. No changes of electrolyte levels were noted. The diet was effective and well tolerated in this treatment of women in climacteric age for obesity.