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  • 1
    Electronic Resource
    Electronic Resource
    The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus (1978)
    Springer
    Diabetologia 14 (1978), S. 301-304 
    Details
    ISSN: 1432-0428
    Keywords: C-peptide ; exocrine pancreas ; amylase ; bicarbonate ; beta-cell function ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these ‘CPR-secretors’ there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p 〈 0.005) and amylase (r =0.7, p 〈 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01223020
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  • 2
    Electronic Resource
    Electronic Resource
    Changes in blood pressure, heart rate, and sympathetic activity on abrupt withdrawal of tiamenidine (HOE 440) in essential hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 449-454 
    Details
    ISSN: 1432-1041
    Keywords: tiamenidine ; rebound hypertension ; plasma noradrenaline ; metanephrines ; urinary catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A limitation of clonidine therapy is the syndrome of rebound hypertension and sympathetic overactivity after withdrawal. Ten patients, four male, six female, aged 28–64 years, with essential hypertension, were treated for one year with an imidazoline derivative, tiamenidine. Blood pressure fell from an average of 178/108 mm Hg pretreatment to 152/86 mm Hg after 1 year. Tiamenidine was then withdrawn in hospital, replaced by identical placebo under single blind conditions and observations made over 96 h. The study was interrupted in five patients (4 patients within 36 h) because blood pressure rose to greater than 30 mm Hg (systolic) or greater than 20 mm Hg (diastolic) above pretreatment values. For the group, blood pressure was maximal at 194/112 mm Hg, 18 h post withdrawal, significantly higher than pretreatment (p〈0.005). Headache, tremor, flushing and insomnia were noted. Saliva production rose 100% at 24 h. Plasma noradrenaline rose within 24 h with an accompanying rise in urinary metanephrine and catecholamine excretion. Tiamenidine appears to share with other imidazolines rebound cardiovascular and autonomic effects following abrupt withdrawal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874654
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637615
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  • 4
    Electronic Resource
    Electronic Resource
    Clinical pharmacological studies with the vasodilator endralazine in patients with renal impairment (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 159-163 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11–52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (βt1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in βt1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest βt1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute βt1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544039
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  • 5
    Electronic Resource
    Electronic Resource
    Absence of an effect of mianserin on the actions of clonidine or methyldopa in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613921
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  • 6
    Electronic Resource
    Electronic Resource
    The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 279-282 
    Details
    ISSN: 1432-1041
    Keywords: Nifedipine ; Doxazosin ; combination ; pharmacokinetics ; liver blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n=6) or doxazosin 2 mg (Group 2, n=6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated. BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy. The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml · min−1 during monotherapy with doxazosin. There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng · ml−1 · h for the 4 study days (Group 2).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271372
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  • 7
    Electronic Resource
    Electronic Resource
    A comparative assessment of amlodipine and felodipine ER: pharmacokinetic and pharmacodynamic indices (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 425-430 
    Details
    ISSN: 1432-1041
    Keywords: Amlodipine ; Felodipine ER ; pharmacokinetics ; blood pressure response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study investigated potential therapeutic differences between Amlodipine 5 mg and Felodipine ER 10 mg in 12 normotensive/borderline hypertensive subjects by comparison of the plasma drug concentration-time profiles and the blood pressure and heart rate responses. There was significantly less trough-to-peak variability in plasma drug concentrations with amlodipine with a ratio of 67%, compared to 37% for felodipine. Correspondingly there was less variability with amlodipine in the blood pressure reductions across the dosage interval. Overall, amlodipine displayed a more consistent hypotensive effect across 24 hours and lower blood pressure values at trough, i. e. 24 hours post-dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315513
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  • 8
    Electronic Resource
    Electronic Resource
    Protein binding of piretanide in normal and uraemic serum (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 311-313 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; uraemia ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of piretanide was assessed by continuous ultrafiltration of sera from six normal subjects and seven uraemic subjects (samples taken immediately pre-dialysis). Throughout the range of piretanide concentrations studied (0.5–4.5 mM), the mean protein binding for uraemic serum was less than that for normal serum. This difference was significant (p〈0.05) at piretanide concentrations of 1.5 mM and above, but not at 1 mM where mean protein binding for uraemic serum was 88.1% compared to 94.2% for normal serum. Analysis of piretanide protein binding characteristics using the Rosenthal plot showed no significant differences between uraemic and normal serum with respect to primary or secondary binding sites. Parallel assessment by the Scatchard method suggests, as expected, that albumin is the principal protein moiety responsible for binding piretanide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637619
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  • 9
    Electronic Resource
    Electronic Resource
    Disopyramide in acute myocardial infarction: Problems with changing pharmacokinetics (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 345-347 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; myocardial infarction ; oral bioavailability ; changing pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the acute phase of myocardial infarction it is recognized that serum disopyramide concentrations may be lower than expected. This has generally been attributed to reduced oral bioavailability. This report describes data obtained routinely from 6 patients with acute myocardial infarction and cardiac dysrhythmias treated initially with intravenous disopyramide. Serum disopyramide concentrations were consistently lower than expected, on average by 2.6 µg/ml. This was interpreted as being due to relatively high drug clearance, calculated as 6.7±1.5 l/h, compared to expected values of 3–4 l/h. Dosage schedules determined on the basis of the acute phase pharmacokinetics subsequently produced higher than predicted concentrations at later times on average by 2.8 µg/ml. Clearance at this time was calculated to be 3.1±0.6 l/h. Thus even with intravenous disopyramide therapy there are problems with changing pharmacokinetic parameters after myocardial infarction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541541
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of cimetidine on the pharmacokinetics, pharmacodynamics and alpha1-adrenoceptor responsiveness of trimazosin in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 301-306 
    Details
    ISSN: 1432-1041
    Keywords: trimazosin ; cimetidine ; pharmacokinetics ; alpha-adrenoceptor antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine treatment on the pharmacokinetics and pharmacodynamics of single doses of trimazosin was studied in 6 normotensive volunteers. Co-administration of cimetidine did not significantly affect the overall magnitude of the hypotensive effect of trimazosin. However, the time profile of the blood pressure response was significantly modified particularly with attenuation of the delayed component. Co-administration of cimetidine did not alter alpha1-adrenoceptor antagonism by trimazosin. There was no significant change in the clearnace and volume of distribution of trimazosin but there was a significant reduction in the area under the concentration-time curve for the metabolite, 1-hydroxytrimazosin. The reduction in the AUC of 1-hydroxy-trimazosin corresponds in time with the attenuation of the delayed hypotensive response. This is consistent with the suggestion that the delayed hypotensive response is related to an active metabolite, probably 1-hydroxytrimazosin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544084
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