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Biomedical subjects

C Dahlöf

Publications and source records attributed to C Dahlöf.

At least 73 records · Page 4Linked to original sources
PubMed1991

Well-being (quality of life) in connection with hypertensive treatment.

Quality of life is often considered to equate how the medical treatment is subjectively perceived by the patient, but ought to include the total impact of the disease/treatment on the patient's emotional, physical, and social well-being. Recently, a proposal for a generally applicable definition of quality of life in health care was put forward. This definition includes general well-being, health, and welfare (external factors), as three fundamental components, and the definition is based on both objective and subjective judgments. General well-being is exclusively and expression of the individual's subjective experience and is based on his or her own qualitative evaluation of well-being in relation to condition, treatments, and experiences. Health is according to the proposed definition, judged both objectively (signs) and subjectively (symptoms). Apart from health and well-being, there is also reason to include objectively registrable factors at the welfare level (external factors) such as the consumption of medicines, number of days in hospital, length of sick leave, need of in-home care, etc. This review is an attempt to elucidate the effects of antihypertensive pharmacotherapy on the patient's general well-being. The topic will be discussed from several points of views (e.g., aims of antihypertensive treatment, occurrence of symptoms in the population, compliance with prescribed treatment, symptom inventories, the concept of quality of life.

Antihypertensive Agents↗
PubMed1991

Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being. The Swedish Diltiazem-Metoprolol Multi-Centre Study Group.

General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120-240-360 mg/day or metoprolol 50-100-200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mmHg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mmHg (SBP/DBP). Target pressures (DBP less than or equal to 90 mmHg and/or a reduction in DBP of greater than or equal to 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120-360 mg and 50-200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.

Adult↗
PubMed1991

Effect of captopril on plasma levels of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea pig.

The effect of exogenous angiotensin II (A II) and the angiotensin converting enzyme (ACE)-inhibitor captopril on plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) has been studied in the pithed guinea pig. Four periods of pre-ganglionic nerve stimulation (PNS, 8 Hz for 30s with 20 min intervals) were applied and the increases of mean arterial blood pressure (delta BP), heart rate (delta HR) and plasma NPY-LI (delta NPY-LI) in response to PNS were analysed in non-pre-treated and captopril pre-treated animals. Captopril (5 mg x kg-1 i.v.) reduced basal blood pressure and delta BP by 20% and 11%, respectively. Infusion of A II (0.5 microgram x kg-1 = min-1 i.v.) caused a significant increase in basal and PNS-induced maximal blood pressure response but reduced delta BP in captopril and non-pre-treated animals by 40% and 16%, respectively. A II elicited a long-lasting increase of basal heart rate by 12% but reduced delta HR by 36% in non-pre-treated animals. However, neither captopril alone nor A II infusion to captopril pre-treated animals significantly changed heart-rate values. The effects of exogenous A II on the cardiovascular responses were abolished by the A II-antagonist saralasin (a bolus injection, 40 micrograms x kg-1 i.v. followed by an infusion, 30 micrograms x kg-1 x min-1), which per se had no significant effect. Captopril pre-treatment reduced basal plasma NPY-LI levels by 38% and delta NPY-LI by 46% in response to PNS 1. However, neither in non-pre-treated nor in captopril pre-treated animals did infusion of A II significantly change the plasma NPY-LI level.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Alpha- and beta-adrenoceptor-mediated effects on nerve stimulation-evoked release of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea pig.

The effect of one beta-adrenoceptor agonist and one antagonist on preganglionic nerve stimulation (PNS)-evoked increase of plasma neuropeptide Y-like immunoreactivity (NPY-LI) was studied in the pithed guinea pig, both in the presence and in the absence of the alpha 2-adrenoceptor antagonist yohimbine. Four periods of PNS (8 Hz for 30 s with 20 min intervals) were applied and the increases of mean arterial blood pressure (delta BP), heart rate (delta HR) and plasma NPY-LI (delta NPY-LI) were analysed. Infusion of the non-selective beta-agonist isoprenaline (0.15 micrograms x kg-1 x min-1 i.v.) tended to reduce delta BP in response to PNS and significantly increased HR at baseline without changing the maximal HR response. Pretreatment with yohimbine (1 mg x kg-1 i.v.) significantly increased delta BP in response to PNS by about 20% without any change in basal HR being observed. The non-selective beta-adrenoceptor antagonist propranolol (5 mg x kg-1 i.v.) significantly reduced delta BP and delta HR both in the presence and in the absence of yohimbine. Isoprenaline infusion enhanced plasma delta NPY-LI by 37% in comparison with the corresponding control. This effect of isoprenaline appeared to be slow in onset and could be blocked by propranolol, which per se did not significantly change plasma delta NPY-LI. Pretreatment with yohimbine caused a three to four-fold increase in plasma delta NPY-LI, which was slightly reduced both in the presence of isoprenaline (-39%) and propranolol (-27%). In conclusion, the sympathetic neurotransmission, also with regard to neuronal NPY, seems to have two adrenergic control mechanisms: one inhibitory and one facilitatory mediated by presynaptic alpha 2- and beta-adrenoceptors, respectively. The facilitatory control mechanism could not be demonstrated if the release of neuronal NPY was already greatly enhanced by alpha 2-adrenoceptors.

Animals↗
PubMed1991

Quality of life in cardiovascular diseases. Emphasis on beta-blocker treatment.

In this article, the issues involved in the measurements of quality of life in clinical trials of cardiovascular drugs are discussed with emphasis on beta-blocker treatment. The extensive documentation available for beta-blockers makes it possible to evaluate different aspects of this class of drugs. Generally, beta-blockers have been shown to be safe with a low frequency of serious side effects. However, results of different studies have shown that this class of drugs affects various aspects of well-being and psychomotor tests both negatively and positively. Adverse effects often associated with beta-blockers are the subjective symptoms that are considered to be related to the central nervous system. Today there is increasing evidence that these can be quantitatively as well as qualitatively reduced by using beta-blockers in a low dose and avoiding high plasma peak concentrations. Considering effects on well-being and psychomotor tests, there seems to be no clinical difference between hydrophilic and lipophilic beta-blockers, when administered in comparable therapeutic dosages, whereas beta 1-selective blockers in clinically relevant doses seem to produce fewer and less severe adverse effects than nonselective blockers. Compared with other classes of cardiovascular drugs, there is no clear evidence of differences in well-being between selective beta-blockers and angiotensin converting enzyme inhibitors or calcium antagonists.

Adrenergic beta-Antagonists↗
PubMed1990

Comparison of CNS-related subjective symptoms in hypertensive patients treated with either a new controlled release (CR/ZOK) formulation of metoprolol or atenolol.

The present study evaluated and compared subjective symptoms in hypertensive patients (N = 83) at therapeutically comparable dosages of a new controlled release (CR/ZOK) formulation of metoprolol (100 mg od) and atenolol (50 mg od). The trial was a 4-week randomized double-blind study preceded by a placebo run-in period. Blood pressure (BP) was recorded 24 hours after intake of last dose. In subpopulations, 24-hour ambulatory BP was recorded and exercise tests performed. Subjective symptoms were evaluated with a previously documented questionnaire (MSE-profile) which has been shown to be sensitive in detecting CNS-related symptoms caused by beta blockers. The MSE-profile includes three dimensions: Contentment, Vitality and Sleep. The results showed that there were no significant differences between the groups in BP reduction either at 24 hours or over the entire 24-hour dose interval. Furthermore, the degree of beta 1-blockade (reduction in exercise-induced tachycardia) 24 hours after last dose did not differ between the groups. There were no significant differences regarding subjective symptoms (Contentment, Vitality, Sleep) between the two treatment groups. An a posteriori power analysis showed that the power to detect a true difference was of an acceptable magnitude. In conclusion, there was no difference in CNS-related symptoms between metoprolol and atenolol at therapeutically comparable dosages indicating that the degree of lipophilicity may be of minor importance for the occurrence of such symptoms.

Adolescent↗
PubMed1990

Tolerability and well-being with metoprolol in a controlled release (CR/ZOK) formulation: a review article.

Extensive research and clinical usage of metoprolol have shown the compound to be safe and well tolerated if the contraindications are taken into consideration. However, as with other beta-blockers, unwanted effects may occur during treatment. Although usually mild, these side effects may be of considerable clinical importance, especially since once initiated, therapy is often life-long. Results of previous studies have indicated that some of these symptoms are associated with high plasma concentrations of the drug. Theoretically, side effects may thus be reduced by administration of metoprolol in a controlled-release formulation (CR/ZOK) which yields relatively low plasma concentrations over approximately 24 hours. Using clinically relevant doses, metoprolol CR/ZOK affects beta 2-adrenoceptor-mediated functions (e.g., broncho-dilatation in asthmatics) less than tablets do. In addition, less leg fatigue during exercise has been reported. The clinical studies published so far indicate that metoprolol CR/ZOK is as well tolerated as or better tolerated than, conventional metoprolol tablets. Furthermore, metoprolol CR/ZOK is tolerated equally or better than atenolol in terms of CNS-related symptoms.

Central Nervous System Diseases↗
PubMed1990

Influence of metoprolol CR/ZOK on plasminogen activator inhibitor (PAI-1) in man: a pilot study.

Recent primary and secondary preventive trials have shown that long-term metoprolol therapy reduces the risk of acute cardiovascular complications. To test whether part of this beneficial long-term effect may be due to effects on the fibrinolytic system, three pilot studies were performed; two in healthy individuals, and one in patients with mild hypertension or uncomplicated atrial fibrillation. The effect of metoprolol CR/ZOK (controlled release) 100-200 mg daily, on plasminogen activator inhibitor activity (PAI-1) in plasma was measured. In addition serum triglycerides and orosomucoid were analyzed. All the individuals were included in double-blind placebo controlled cross-over trials with treatment periods ranging from 4 days to 3 weeks. During metoprolol therapy PAI-1 values were reduced, while orosomucoid and triglyceride levels were unchanged. A linear inverse correlation was found between fibrinolysis and PAI-1 activity in plasma, indicating that PAI-1 activity serves as an indicator of fibrinolysis. PAI-1 activity and triglycerides were significantly correlated during placebo and metoprolol therapy. In conclusion, our results in these pilot studies suggest that metoprolol enhances fibrinolytic activity as seen by reduced PAI-1 activity. These results should be further confirmed and put into relation of clinical effects of the therapy.

Adult↗
PubMed1990

Side effects of beta-blocker treatments as related to the central nervous system.

During the last decade beta-adrenoceptor antagonists have become one of the first-line treatments for hypertension. Generally, they have been shown to be safe with a low frequency of serious side effects. However, minor subjective symptoms, usually considered to be CNS-related, have been reported for all beta-blockers used. Thus, all beta-blockers on the market seem to have a high benefit:risk ratio; independent of their physicochemical properties and pharmacodynamic profile, however, they seem to cause CNS-related side effects to about the same extent. These minor side effects, the mechanisms of which are unclear, consist of subtle effects on general well being, decreased initiative, a depressed frame of mind, and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. The results so far available have been obtained primarily by using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect. Rather, the plasma concentration of the beta-blocking drug (degree of beta-blockade) seems to be the major determinant of whether or not CNS-related symptoms appear in susceptible patients.

Adrenergic beta-Antagonists↗
PubMed1990

Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients.

Felodipine, a dihydropyridine calcium antagonist, was given double-blind in a crossover design comparing once-daily doses of 20 mg felodipine extended-release (ER) tablets with placebo in 12 hypertensive patients. A 2-h intravenous infusion was given after a placebo washout. After oral felodipine, blood pressure (BP) was significantly lower than after placebo, both after the first dose and after 2 weeks of treatment. Supine BP 24 h after the first dose of placebo and felodipine was 159/97 and 153/92 mm Hg (p less than 0.01/0.05), respectively. Corresponding BPs at 2 weeks were 158/99 and 144/89 mm Hg (p less than 0.01/0.01). Approximately 75% of the maximal and 60% of the trough effect at steady state were obtained already after the first dose. The plasma concentration (CpF) vs. time curve after felodipine ER was relatively flat. After oral felodipine, a linear correlation was found between BP reduction and logarithmic CpF. After intravenous administration, CpF correlated well with a hyperbolic function. These data indicate that there is an almost linear relation between BP reduction and log CpF in the range from 2-20 nmol/L, and that little additional effect is to be expected above approximately 20 nmol/L. No hysteresis was found for the relationship between CpF and BP reduction. The absolute bioavailability of felodipine ER was 22%.

Adult↗
PubMed1990

Minor Symptoms Evaluation (MSE) Profile--a questionnaire for assessment of subjective CNS-related symptoms.

Minor Symptoms Evaluation Profile (MSE-profile) is an instrument for the assessment of subjective CNS-related symptoms and has recently been documented. This self-applied questionnaire includes 24 items and uses a visual analogue scale to record perceived symptoms. Based on a subjective grouping followed by a principal component analysis of the results of 374 individuals to confirm the grouping, 15 out of the 24 items were formed into three dimensions: Contentment (7 items), Vitality (5 items) and Sleep (3 items). The Cronbach's alpha coefficient used to evaluate the internal consistency of these dimensions was 0.81, 0.81 and 0.77, respectively. Compared with the equivalent dimensions of other questionnaires for measurement of health-related quality of life, the dimensions of the MSE-profile were found to be relevant. Furthermore, the MSE-profile showed good discriminative ability to distinguish symptom profiles of patients with other diseases/complaints than hypertension. It can be concluded that the MSE-profile is practically useful, reliable and sensitive enough for the assessment of subjective CNS-related symptoms that might affect the patient's well-being/quality of life.

Adrenergic beta-Antagonists↗
PubMed1990

Quality of life/subjective symptoms during beta-blocker treatment.

beta-receptor antagonists have for many years been considered appropriate alternatives in the primary management of mild to moderate hypertension. Generally, they have been shown to be safe with a low frequency of serious side-effects. Among the predictable and usually doserelated side-effects are bradycardia, bronchospasm, hypotension, muscle fatigue and cold extremities. Examples of unexpected side-effects are gastrointestinal symptoms such as nausea and disturbed intestinal motility, skin reactions, sexual dysfunction, as well as effects related to the central nervous system (CNS) such as emotional disturbances. The CNS-related side-effects, the mechanisms of which are unclear, consist of subtle effects on general well-being, decreased initiative, a depressed frame of mind and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. Thus, all beta-blockers on the market seem to have high benefit-risk ratio, but independent of their physiochemical properties and pharmacodynamic profile, they seem to cause side-effects to about the same extent. The results so far available have been obtained by primarily using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side-effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Adrenaline-induced enhancement of the blood pressure response to sympathetic nerve stimulation in adrenal demedullated pithed rats.

The influence of the prejunctional beta-adrenoceptor-mediated control mechanism of noradrenaline release on the cardiovascular response to preganglionic nerve stimulation (PNS) and the role of adrenaline as endogenous activator of this facilitatory mechanism were studied in pithed rats. The increases in mean arterial blood pressure and heart rate responses to eight PNS (0.8 Hz, 1 ms, 75 V, for 20 s at 12 min intervals) were measured in control, adrenal demedullated and sham-operated pithed rats, respectively. Repeated stimuli of the sympathetic outflow elicited similar blood pressure responses in control and sham-operated rats, whereas the blood pressure responses were attenuated in adrenal demedullated rats. Administration of the non-selective beta-adrenoceptor antagonist propranolol (5 mg x kg-1, i.v.) decreased the blood pressure response in control, but not in adrenal demedullated rats. The increase in heart rate during PNS was abolished in both groups after administration of propranolol. Infusion of adrenaline (0.06 microgram x kg-1 x min-1) increased the circulation levels of adrenaline from 0.4 nmol x l-1 to 4.8 nmol x l-1, but did not modify the blood pressure response to PNS in control rats. In adrenal demedullated rats, however, the blood pressure response to PNS was enhanced during as well as after the infusion of adrenaline. This facilitatory effect of adrenaline on the blood pressure response in adrenal demedullated rats was blocked by pretreatment with propranolol (5 mg x kg-1, i.v.). Taken together the present findings give further support to the hypothesis that neuronal adrenaline of adrenal medullary origin is the endogenous agonist at prejunctional beta-adrenoceptors mediating a facilitation of neuronal noradrenaline release.

Adrenal Medulla↗
PubMed1989

Documentation of an instrument for assessment of subjective CNS-related symptoms during cardiovascular pharmacotherapy.

The aim of this work was to develop and initiate the documentation of an instrument for the assessment of subjective CNS-related symptoms occurring during cardiovascular pharmacotherapy. The self-applied questionnaire developed for minor symptom evaluation (MSE profile) includes 24 items and uses a visual analogue scale to record symptoms. Three different studies were performed using a total of 86 healthy volunteers. Based on a subjective grouping followed by principal component analysis to confirm the grouping, three dimensions-contentment (eight items), vitality (five items), and sleep (three items)-were formed. The Cronbach's alpha coefficient, used to evaluate the internal consistency of these dimensions, was found to be 0.90, 0.88, and 0.85, respectively. To validate the MSE profile, the subjective symptoms of two classes of drugs with well-known symptom profiles, a nonselective, beta-blocker (propranolol) and a benzodiazepine (oxazepam), were compared in placebo-controlled randomized double-blind crossover studies. The obtained results indicate that the symptom profiles were different but were compatible with the previously reported effects of these compounds. It can be concluded that the MSE profile is practical, useful, and sensitive enough to also detect subtle drug-induced effects.

Brain↗
PubMed1989

Acyclovir concentrations in serum and cerebrospinal fluid at steady state.

A long-term clinical trial of acyclovir, 800 mg tid, as a therapeutic agent in multiple sclerosis (MS) is in progress. In three patients paired serum and cerebrospinal fluid (CSF) specimens were sampled after one, four, eight and twelve months of continuous treatment. These samples were collected 1.5 h before or 1.5 h after an oral dose. Acyclovir concentrations were assessed by radioimmunoassay. In the CSF, the acyclovir concentration was relatively stable, with a mean of 0.83 microM, while the serum acyclovir concentration was variable with mean peak and trough concentrations of 4.08 and 2.47 microM, respectively. In two other MS patients the acyclovir concentration time profile in serum and CSF was studied at steady state during the 8 h dose interval. In this study the acyclovir concentration in the CSF was only slightly affected by the fluctuations in serum and the acyclovir CSF/acyclovir serum ratio was apparently not influenced by the blood-brain barrier function. We found no indication of an accumulation of acyclovir in cerebrospinal fluid after one to twelve months of oral treatment.

Acyclovir↗
PubMed1989

CNS-related subjective symptoms during treatment with beta 1-adrenoceptor antagonists (atenolol, metoprolol): two double-blind placebo controlled studies.

1. Whilst a number of studies have investigated whether metoprolol and atenolol, the most widely used beta 1-adrenoceptor antagonists, differ with regard to CNS-related subjective symptoms, few placebo-controlled studies using standardised questionnaires have been performed. 2. In the present report, the findings of two randomised, double-blind, cross-over studies in healthy volunteers are presented. The subjects were treated with placebo and atenolol (100 mg once daily) (Study 1) and metoprolol (100 mg once daily) and placebo (Study 2). 3. Subjective experiences were evaluated using a standardised instrument, the Minor Symptoms Evaluation-profile (MSE-profile), which was filled in 4, 8 and 24 h after intake of the tablets. A Type A questionnaire was also completed by the subjects. 4. At 4 h both metoprolol and atenolol were found to affect negatively vitality and contentment, but these effects had declined after 8 h. A significant adverse effect on sleep was shown for atenolol compared with placebo, while no negative effect was observed for metoprolol. No significant differences were found in relation to Type A behaviour and beta-adrenoceptor blockade. The number of subjects with Type A personality was, however, low. 5. The results of the studies indicate that the subjective symptoms of the beta 1-adrenoceptor blockers are mild, and that the effects appear consistently with the recognised pharmacokinetic profiles of the two drugs.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of the thiazide diuretic bendroflumethiazide on salivary flow rate and composition.

Thiazide diuretics are among the first-line alternatives in the treatment of primary hypertension. The effects of thiazide treatment on salivary production are, however, little studied and the results so far available are not decisive. The aim of the present study was to evaluate and compare salivary flow rate and composition during treatment with the thiazide diuretic bendroflumethiazide in a low dose (2.5 mg o.d.) and placebo. The study was performed with a randomized, double-blind, cross-over design (2 x 2 wk) in 34 healthy volunteers. The treatment periods were separated by a wash-out period of 2 wk. Resting and stimulated whole saliva was sampled three times daily on scheduled days during the treatment periods. Flow rate was assessed for resting saliva, whereas flow rate, pH, buffer capacity, amount of total proteins and concentrations of sodium, potassium, calcium, phosphate and magnesium were measured for stimulated whole saliva. No effect of bendroflumethiazide on the resting salivary flow rate could be detected, while the stimulated flow rate was significantly reduced by about 10% during the thiazide treatment. The total sodium output was significantly decreased by approximately 30%, without any detectable change in total potassium output. All other variables of stimulated whole saliva studied were not different from placebo. It is concluded that treatment with bendroflumethiazide in a low dose significantly reduces the stimulated whole salivary flow rate and total sodium output in healthy volunteers.

Adolescent↗