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Biomedical subjects

O L Pedersen

Publications and source records attributed to O L Pedersen.

At least 37 records · Page 2Linked to original sources
PubMed1989

Differential effects of isradipine and atenolol on peripheral hemodynamics and arterial compliance.

In a double-blind parallel-group randomized study, 28 patients with essential hypertension (World Health Organization class I/II) were allocated in equal numbers to one of two groups for treatment with either isradipine 5 to 20 mg twice daily or atenolol 50 to 100 mg once daily. At the end of the study, 12 patients were evaluable in the isradipine group and nine in the atenolol group. Assessments at baseline and after 20 weeks of treatment included arterial and venous compliance, mean peripheral perfusion pressure, heart rate, and digital vascular resistance using photoplethysmography. Isradipine had a direct relaxing effect on the arterioles, revealed by a significant increase in arterial compliance and a concomitant normalization of the digital vascular resistance. Atenolol had no significant effect on these parameters but, as expected, it lowered the heart rate, which was not affected by isradipine in the long term. The venous compliance remained low in both groups and, since isradipine--unlike atenolol--is known to have venodilating properties in vitro, its lack of effect in vivo is most likely due to reflex activation of sympathetically mediated venous tone. Because of the preference of isradipine for the arterial side of the peripheral vascular tree, the mean peripheral perfusion pressure remained higher in this group than in the atenolol group, although central systemic blood pressure was lowered equally and satisfactorily in both groups.

Antihypertensive Agents↗
PubMed1989

Cortisol and treatment of depression: predictive value of spontaneous and suppressed cortisol levels and course of spontaneous plasma cortisol.

In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n = 72), 2) 2h after oxazepam suppression (45 mg, n = 28; 60 mg, n = 37) and 3) 16 h after dexamethasone suppression (2 mg, n = 71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n = 55) and 5 weeks' treatment (n = 36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.

Adult↗
PubMed1989

Comparison of indapamide and hydrochlorothiazide plus amiloride as a third drug in the treatment of arterial hypertension.

In a randomized, double-blind crossover trial, indapamide (IND) 2.5 mg and hydrochlorothiazide 25 mg + amiloride 2.5 mg (HCTZ + A) were found to be equally effective in reducing blood pressure (BP) in 13 patients with moderate to severe hypertension already receiving chronic treatment with a beta blocker and a vasodilatator (supine BP during run-in: 169/103 +/- 21/5 mmHg; on IND: 149/91 +/- 21/14 mmHg; on HCTZ + A 144/88 +/- 23/5 mmHg). Both drugs induced insignificant reductions in body weight, and no change in plasma volume was seen. Serum potassium was significantly reduced on both regimens--the values recorded on IND being significantly lower than those seen on HCTZ + A. Values below 3.0 mmol/l were found in two patients receiving IND, but no subjective side effects were reported. Hyperuricemia occurred with the same frequency on both regimens. It is concluded that IND, just like the thiazide diuretics, is useful as the third drug in patients needing triple drug therapy to control BP, but metabolic adverse effects are not avoided by the choice of this drug.

Adult↗
PubMed1989

Pharmacodynamics of BAY K 8644 alone and in combination with dobutamine in the isolated rabbit heart.

The haemodynamic effects of the Ca-agonist BAY K 8644 alone and in combination with the selective beta-I-adrenoceptor agonist dobutamine were studied in the isolated rabbit heart. BAY K 8644 produced a concentration-dependent increase in contraction amplitude and shortening velocity, oxygen consumption and heart rate. In combination with a small fixed concentration of dobutamine (40 nM), Bay K 8644 produced similar alterations. When Bay K 8644 was infused at a fixed concentration (38 nM), dobutamine likewise produced similar increments in contraction amplitude, shortening velocity and heart rate, whereas oxygen consumption was considerably argumented. Both BAY K 8644 and dobutamine showed definite positive inotropic effects in the isolated rabbit heart. Combination of the two drugs did not yield a stronger positive inotropic effect than that seen on single drug administration, and oxygen consumption was even increased.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Afternoon plasma cortisol in relation to depression. A replication study.

In 37 consecutive depressed inpatients afternoon plasma cortisol (1500-1520 h) was measured in 3 ways: 1) spontaneously; 2) 2 h after oral administration of 60 mg oxazepam; and 3) 16 h after oral administration of 2 mg dexamethasone. Both oxazepam and dexamethasone caused a significant suppression of cortisol secretion. Spontaneous and suppressed cortisol levels correlated significantly to stress/distress items on the Hamilton Rating Scale for Depression (sum of items 8, 9, 10 and 12), whereas no correlations to age, or type of depression were found. In an earlier similar study of 35 patients both spontaneous and suppressed cortisol levels correlated significantly with age, type and severity of depression as well as with the stress/distress items. Those patients were older, more depressed (HRSD-17) and had higher stress/distress scores compared with the present sample of 37 patients. The consistent finding of a correlation with the stress/distress items suggest that this factor is important in relation to the hypersecretion of cortisol during depression and this may explain the limited diagnostic power of spontaneous and suppressed cortisol levels.

Adult↗
PubMed1987

Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine.

The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine (PN 200-110), on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p less than 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p less than 0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p less than 0.01 and p less than 0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p less than 0.01) and an increase in diuresis (p less than 0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressure-regulating response.

Blood Pressure↗
PubMed1987

Acute natriuresis induced by inhibition of proximal tubular reabsorption of sodium and water in hypertensives following acute calcium entry blockade with nifedipine.

To elucidate the renal effects and especially the natriuretic properties of calcium entry blockers, we studied the effect of sublingual nifedipine 20 mg in 16 patients with mild to moderate essential hypertension. The lithium clearance technique was utilized and constant infusion technique was employed to measure glomerular filtration rate (GFR) and renal plasma flow (RPF). Nifedipine induced a significant reduction of systolic and diastolic blood pressure and an increase in heart rate. RPF increased and renal vascular resistance fell significantly, whereas GFR was unchanged. A significant increase in diuresis and in clearance of sodium and lithium was seen. The absolute and fractional proximal reabsorption of sodium and water was reduced. The absolute distal reabsorption increased significantly. The results indicate that the natriuretic action of nifedipine in hypertensives is a proximal tubular event.

Blood Pressure↗
PubMed1986

The quantitative aspect of photoplethysmography revised.

The overall transfer function of a photoplethysmograph (PPG) converting changes in intravascular volume to changes in recorder pen deflection was investigated. The specifications of the apparatus working as a red cell densitometer were assessed in vitro, and it was found that PPG output is a logarithmic function of red cell density roughly in accordance with the Lambert-Beer theorem. In an in vivo experiment it was found that PPG output is also a logarithmic function of digital intravascular volume as assessed by means of air plethysmography. It is suggested that the equation for this in vivo function is different because of a dual action of stasis, producing increases in both intravascular volume and haematocrit. Although the relative contributions of the two disparate phenomena are not assessed further, it is concluded that their joint action on PPG output can be described by a monologarithmic function. In the Appendix, sources of non-linearity in the electronics of PPG are pointed out and instructions for the use of an exponential amplifier which will linearize the overall transfer function are given.

Blood Volume↗
PubMed1985

Orthostatic side effects of clomipramine and citalopram during treatment for depression.

Orthostatic hypotension, the clinically most important side effect in treatment with tricyclic antidepressants, was investigated in a double-blind study with clomipramine and the selective serotonin reuptake inhibitor citalopram given for 5 weeks. All patients were initially given placebo for 1 week. In the clomipramine group (n = 17) a significant orthostatic drop in the systolic blood pressure was observed during treatment; this remained significant over the whole investigational period. A curvilinear correlation was demonstrated between the orthostatic drop in systolic blood pressure and the plasma levels of clomipramine and desmethylclomipramine. The most pronounced orthostatic reaction was thus seen in 1-2 weeks, at plasma levels of 25-75 micrograms/l (clomipramine). The correlation between the subjective symptoms and the measured orthostatic drop was poor, as was the correlation between the subjective symptoms and the plasma levels of the two active compounds. The change in orthostatic heart rate during clomipramine treatment was insignificant. In the citalopram group (n = 15) no significant changes in orthostatic blood pressure or heart rate were demonstrated during treatment and these patients had no orthostatic complaints.

Adult↗
PubMed1985

Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients.

Thirteen elderly depressed patients (age 60-82 years) were treated for 5 weeks with a fixed dose of amitriptyline 100 mg (sustained release preparation). In all patients the sum of concentrations of amitriptyline and nortriptyline exceeded 130 micrograms/l, which is the recommended plasma level. Cardiovascular side effects were recorded by monitoring heart rate, blood pressure, standard ECG and systolic time intervals. During treatment, a transient increase in the supine heart rate was observed without significant changes in the supine blood pressure. The orthostatic drop in blood pressure was markedly increased during treatment without a compensatory increase in heart rate, and these changes remained significant during the whole investigational period. PQ and QRS were significantly increased during treatment, and significant changes in the systolic time intervals were found indicating impairment of myocardial conduction and contractility. In three patients medication was discontinued due to cardiovascular side effects.

Aged↗
PubMed1985

Renal uric acid handling is not affected by beta-adrenoceptor blockade in normotensive subjects.

Nine normotensive healthy females received timolol 5 mg daily for a 4-day period and subsequently 20 mg daily for another 4-day period. None of the two dosages of timolol caused significant changes in serum uric acid or 24-h urinary fractional excretion of uric acid. Thus the increments of serum uric acid previously found in hypertensive patients is not likely to be caused by beta-adrenoceptor blockade per se.

Adrenergic beta-Antagonists↗
PubMed1984

Changes in blood chemistry in hypertensive patients during propranolol therapy.

Propranolol induced changes in blood plasma chemistry were followed in thirty hypertensive patients (WHO I-II) who were seen each week during 14-15 weeks. The initial 4 weeks were a drug free period and the next 2 weeks were a drug adjustment period. After that the patients were on an unchanged propranolol dose for 8 weeks (40, 80 or 160 mg four times daily). For all observed changes the correlation was studied to (1) dose, (2) free and total simultaneously determined plasma concentration and (3) free and total average plasma concentration of unchanged drug during the preceding 24 h period. Total protein and albumin did not change significantly. After 4 and 8 weeks on the final dose orosomucoid was increased significantly (by 10%) compared with the value from the end of the drug free period. Creatinine rose significantly during the initial 4-6 weeks therapy to remain at the same level during the last 4 weeks. Urate was increased at the two lowest dose levels. Total cholesterol fell significantly (5%) while triglycerides increased significantly (16%). T4 rose significantly, T3 fell and r-T3 rose significantly in a dose dependent way. Interindividually r-T3 was the only biochemical change showing a significant relationship to the propranolol plasma concentration. The relationship reached the highest level of significance to the average 24 h free concentration.

Adult↗
PubMed1984

Effects of two new Ca-entry blockers bepridil and nitrendipine on isolated vessels.

The effects of nitrendipine and bepridil were studied in isolated rings of human crural veins contracted by noradrenaline (NA) or potassium (K). Both drugs had a concentration dependent inhibitory effect on active tone and shifted the NA and K concentration-response curves to the right in a non-parallel manner and reduced the maximum contractile response. Both drugs had a more potent inhibitory effect on K than on NA-induced contractions. Nitrendipine was far more potent in inhibiting the K-induced contractions than bepridil while the drugs were equipotent in inhibiting NA-induced contractions. Human veins were less sensitive than rat aorta to the inhibitory effect of nitrendipine. In contrast to nitrendipine the effect of bepridil was gradual and slow in onset. The inhibitory effect of both drugs was strong and long-lasting and resistant to washout procedures. Both drugs effectively eliminated spontaneous mechanical activity and reduced K-induced contractions in rat portal veins. The results support that nitrendipine and bepridil are effective vasodilators in arteries as well as in veins. The main action of both nitrendipine and bepridil seems to be attributed to an inhibitory effect on cellular Ca-entry.

Adult↗
PubMed1984

Plasma level monitoring of antidepressants: theoretical basis and clinical application.

For TCAs there is a strong rationale for drug level monitoring in clinical therapy. Therapeutic drug concentration ranges have been established in controlled studies with NT, imipramine, and AT. It has been shown that by appropriate choice of antidepressant and close monitoring of drug levels, treatment with antidepressants in elderly and other risk patients can be carried out effectively and safely, reducing the use of electroconvulsive therapy. Finally, the practical clinical use of antidepressant concentration measurements is now feasible and not expensive, and the analytical procedures can be established in most hospital settings. On the basis of these premises the following can be concluded: Plasma level monitoring should be used as a routine for imipramine, NT, and AT. Further plasma level studies on other antidepressants and in overdose cases should be initiated. Plasma level monitoring is indispensable in clinical research on antidepressants (trials, new drugs, toxicology). Pharmacokinetic considerations may be useful to determine which receptor effects are clinically relevant in therapy and toxicology.

Amitriptyline↗