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Biomedical subjects

Thomas Hedner

Publications and source records attributed to Thomas Hedner.

48 records · Page 3Linked to original sources
PubMed2002

Comparison of home and office blood pressure in treated hypertensives in the Nordic Diltiazem (NORDIL) Study.

The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular morbidity and mortality in calcium-antagonist-based treatment with diltiazem and conventional diuretic/beta-blocker-based treatment in essential hypertension. The objective of the present sub-study was to compare self-measured home blood pressure with office blood pressure at a time-point in the study when the patients' blood pressures had been treated to the level that the investigators conceived to be the blood pressure target. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74 years at health centers in Norway and Sweden who had diastolic blood pressure (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but fairly representative for the entire study population regarding baseline characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures (3.1 mmHg, p < 0.001) were significantly lower at home than in the office. Pearson correlation coefficients between the respective office and home readings were statistically highly significant (p < 0.001), but of moderate strength ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and systolic blood pressures, respectively. Altman plots also gave statistical support to some inconsistency between the two methods of measurements. Pearson correlation coefficients between afternoon and morning measurements showed strong relationships with r-values >0.9 for both blood pressures and heart rate. The Altman plots also suggested excellent consistency between afternoon and morning measurements. Thus, motivated and trained hypertensive patients can perform home recordings of blood pressure and heart rate with precision; however, there are differences between recordings at home and in the investigators' offices that suggest some degree of "white coat effect" in these treated hypertensives.

Aged↗
PubMed2002

Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study.

BACKGROUND: The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/beta-blocker-based treatment, with respect to cardiovascular morbidity and mortality. OBJECTIVE: To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. METHODS: The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50-74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/beta-blocker group - a significant difference in SBP (P < 0.001). RESULTS: The incidence of the primary endpoint - a composite of cardiovascular death, cerebral stroke and myocardial infarction - was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98; P = 0.032), DBP >/= 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97; P = 0.030) and pulse pressure >/= 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87; P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment-subgroup interaction analyses were not statistically significant. CONCLUSIONS: Compared with a conventional diuretic/beta-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.

Adrenergic beta-Antagonists↗
PubMed2002

The clinical profile of the angiotensin II receptor blocker eprosartan.

Angiotensin II receptor antagonists block angiotensin II type 1 (AT1) receptors and reduce the pressor effects of angiotensin in the vasculature. By this mechanism, they induce similar pharmacological effects to angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure (BP). However, AT1 antagonists differ from ACE inhibitors with respect to side effects, and induce less cough, which is related to bradykinin activation. Within the class of angiotensin II antagonists, eprosartan differs from other currently clinically available agents in terms of its chemical structure and its dual pharmacological mode of action. Eprosartan acts not only at vascular AT1 receptors but also at presynaptic AT1 receptors, causing inhibition of sympathetically stimulated noradrenaline release. Eprosartan is not metabolized by cytochrome P450 enzymes and therefore has a low potential for metabolic drug interactions, which may be of importance when treating the elderly and patients on multiple drugs. In clinical trials eprosartan has proven to be at least as effective as the ACE inhibitor enalapril in reducing BP, but with a significantly lower incidence of side effects. Eprosartan is safe, effective and well tolerated in long-term treatment, either as monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.

Acrylates↗
PubMed1995

Morphine and morphine metabolite concentrations in cerebrospinal fluid and plasma in cancer pain patients after slow-release oral morphine administration.

In 34 cancer patients treated with chronic slow-release oral morphine, plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined by high-performance liquid chromatography (HPLC). Both plasma and CSF morphine, M3G and M6G, concentrations were linearly related to dose of morphine. At steady state, the mean +/- SEM CSF/plasma morphine concentration ratio was 0.8 +/- 0.1. In plasma and CSF, the mean steady-state concentrations of M3G and M6G substantially exceeded those of morphine where the mean CSF M/M3G/M6G ratio was 1:47:5 (weight basis), 1:34:4 (molar basis) and the mean plasma ratio was M/M3G/M6G 1:150:23 (weight basis), 1:109:17 (molar basis). The mean M3G and M6G concentrations in CSF at steady state were 15-18% of those found in plasma. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. Since CSF M6G concentrations were high, M6G could, however, contribute to pain relief. We conclude that after oral administration of slow-release morphine, there is a significant passage of the morphine glucuronide metabolites to the CSF and that the M3G and M6G metabolites in CSF are in the concentration range where they may have an influence on analgesia.

Administration, Oral↗
PubMed1993

CSF and plasma concentrations of morphine and morphine glucuronides in cancer patients receiving epidural morphine.

Thirty-five cancer patients, treated with chronic epidural morphine, were assayed for plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations (Css min) of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by high performance liquid chromatography (HPLC). A linear dose-concentration relationship was found for the 3 substances in plasma and for morphine and M3G in CSF. The mean +/- S.E.M. CSF/plasma morphine ratio was 158 +/- 43. In CSF, the concentrations of morphine exceeded those of the metabolites substantially and, normalized to morphine, the mean CSF M/M3G/M6G ratio was 1:0.05:0.02. In plasma, the metabolite concentrations were higher than the parent drug and the plasma M/M3G/M6G ratio was 1:12:3. The mean M3G and M6G concentrations in CSF were 40-60% of those found in plasma. Indication of cerebral formation of M3G was found in 1 patient. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. CSF M6G concentrations were low and did not contribute to any detectable analgesia. We conclude that after epidural administration of morphine, the M3G and M6G metabolites in CSF are low compared to unchanged morphine and seem to have little influence on analgesia. However, the fact that a significant passage of the glucuronide metabolites occurs to the CSF may indicate a role in morphine analgesia after other routes of administration.

Analgesia, Epidural↗
PubMed1992

Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat.

The effects of the major morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, on nociception were assessed by the tail-flick, hot-plate and writhing tests in the rat. Morphine-3-glucuronide (M3G) 1.1 x 10(-9) mol (0.5 micrograms) or saline was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) followed by a second injection of 2.0 x 10(-10) mol (0.1 microgram) or 2.0 x 10(-11) mol (0.01 microgram) morphine-6-glucuronide (M6G) 10 min later. Administration of M3G (i.c.v.) significantly attenuated the antinociceptive effects of M6G in the hot-plate test. After i.t. administration, the antinociceptive effect of M6G in all three tests was significantly reduced in the M3G pretreated group compared to the group receiving saline. The ventilatory effects of 4.0 x 10(-9)-1.0 x 10(-8) mol (2-5 micrograms) M6G and 1.7-2.2 x 10(-8) mol (8-10 micrograms) M3G given i.c.v. were studied by a whole-body plethysmographic technique in halothane anaesthetized rats. Separate groups of rats received M3G followed by M6G injection or vice versa. In animals receiving M3G there was a prevention or attenuation of the M6G induced depression of respiratory frequency, tidal volume and minute ventilation compared to control groups receiving M6G in combination with saline. These results show that M3G may functionally antagonize the central antinociceptive effects as well as the ventilatory depression induced by M6G. Interestingly, M3G was more potent in antagonizing the M6G-induced analgesia after i.t. administration than that after i.c.v. administration, which may suggest that the spinal cord is more sensitive to the non-opioid excitatory effects of M3G than supraspinal structures.

Analgesics↗
PubMed1991

Pain characterization in cancer patients and the analgetic response to epidural morphine.

In 48 patients with pain related to malignancy, a pain characterization was performed during oral opioid therapy. After an optimal epidural morphine regimen had been established, the alteration in pain relief was evaluated by means of a visual analogue scale. The CSF and plasma morphine concentrations at minimum steady state were then analysed in 28 patients and related to the degree of pain relief. The efficacy of the spinal treatment ranked in the following order: somatic greater than visceral greater than radiating = 0, but the difference was only significant between the somatic and radiating pain groups. There was a tendency for continuous pain to be better relieved than intermittent pain. No correlations were found between the CSF or plasma morphine concentrations and the degree of pain relief, suggesting that not all pain impulses are modulated in a dose-dependent manner by morphine at the spinal level. Pain characterization may be instrumental in providing an optimal spinal opioid analgesia in malignancy. Moreover, there is a need for better defined diagnostic criteria for clinical pain characterization.

Aged↗
PubMed1987

CSF and plasma morphine concentrations in cancer patients during chronic epidural morphine therapy and its relation to pain relief.

Seventeen patients with advanced cancer pain, treated with chronic epidural morphine, were studied. Minimum plasma and CSF morphine concentrations (CSSmin) were determined at pharmacokinetic steady state. A linear relationship was found between epidural morphine dose and concentrations obtained in plasma (r = 0.92) as well as CSF (r = 0.90). The line for best fit was much steeper for CSF than for plasma. The CSF/plasma concentration gradient of morphine at CSSmin was 132 +/- 31 (mean +/- S.E.M.). Large interindividual variations of morphine concentrations in CSF were found. It is suggested that the variations are due to substantial differences in transdural morphine diffusion between individuals. No correlation was found between pain relief, evaluated with a visual analog scale, and CSF morphine concentrations at pharmacokinetic steady state, when calculated in 9 patients. Mean duration of treatment was 104 days (range 14-366) and the daily dose was increased from 18 +/- 2 to 87 +/- 31 mg/day (mean +/- S.E.M.). A total of 39 epidural catheters were inserted in 14 patients. The catheters were patent for 2-223 days with a mean of 38 days. When re-examined later during treatment, 2 out of 8 patients demonstrated decreased CSF morphine concentrations in spite of increased doses given. One patient with extremely high dose demand is reported on separately and data supporting the concept of a combined spinal and systemic brain morphine effect in such cases are presented. Side effects were not a major problem but the possibility of infectious complications should be considered during chronic epidural morphine therapy.

Adult↗