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  • 1
    ISSN: 1432-1041
    Keywords: nifedipine ; cimetidine ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.
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  • 2
    ISSN: 1432-1041
    Keywords: Antihypertensive agents ; clonidine ; methyldopa ; hypertensive rebound ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The results of a titrated-dose cross-over comparison of clonidine with methyldopa are reported. Only one third of those entering the trial completed it. The blood pressure lowering effect of the two drugs is seen to be very similar. Patients experienced significantly more dry mouth whilst on clonidine but sedation was equally distributed over the two treatments. A hypertensive rebound occurred in some patients after sudden withdrawal of clonidine. The place of this new compound in routine management of hypertension is discussed.
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  • 3
    ISSN: 1432-1041
    Keywords: Antihypertensive therapy ; alpha adrenoceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Indoramin, a new antihypertensive drug shown to have cardioinhibitory and alpha adrenoceptor blocking activity in animals, was administered to patients with benign essential hypertension. Single oral doses between 0.1 and 1.0 mg/kg produced dose dependent falls in diastolic arterial pressure without increasing the heart rate. The arterial pressure response to intravenous noradrenaline was diminished in patients taking indoramin, but the response to intravenous angiotensin II and heart rate responses to intravenous isoprenaline were unaltered. Double blind cross-over comparison of indoramin with placebo in 8 patients on continuous oral therapy at maximally tolerated doses, 60–150 mg daily, showed that indoramin significantly lowered diastolic arterial pressure, but that the falls were modest, 7.6 mm Hg lying, 7.1 mm Hg standing and 9.3 mm Hg after exercise. The dose limiting side effect was sedation.
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  • 4
    ISSN: 1432-1041
    Keywords: Levodopa ; Gastric emptying ; paracetamol ; elderly subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Paracetamol absorption and 99Tc-DTPA measurements have been used to determine the influence of levodopa on gastric emptying in 8 healthy elderly volunteers. In the absence of levodopa 7 subjects showed a rapid gastric emptying pattern by gamma-camera and a single major peak in the plasma concentration-time curve of paracetamol. One subject showed two rapid phases of gastric emptying separated by a period of negligible emptying and had 2 separate peaks in the paracetamol plasma concentration-time curve. In the presence of levodopa, the gamma-camera data for 6 subjects showed a pattern of gastric emptying consisting of 2 rapid phases separated by a plateau. In each case secondary peaks in the plasma concentration-time curve of paracetamol occurred about 30 min after the end of the plateau. The time to 90% emptying on the gamma scan was increased significantly from 40 min to 65 min in the presence of levodopa. Comparison of the present data with those reported previously indicates that levodopa affects gastric emptying in the both elderly and young volunteers to a similar extent.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: trazodone ; imipramine ; anticholinergic effects ; ECG ; antidepressants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The electrocardiographic and anticholinergic effects of trazodone (150 mg) and imipramine (75 mg) were investigated in 8 healthy volunteers. Both agents increased the QTc interval and decreased T wave height, but the effects occurred earlier with trazodone (from 30 min onwards) than with imipramine (150 and 180 min after dosing). Both drugs decreased heart rate, imipramine at 30 and 60 min and trazodone at 90 min. After 120 min, heart rate began to increase with imipramine an effect which was not seen with trazodone. Salivary volume was significantly decreased by imipramine at 120 and 180 min whereas trazodone did not influence salivary volume. Plasma levels of trazodone and imipramine were significantly related to the decrease in T wave amplitude. The increase in QTc interval correlated significantly with the plasma level of imipramine. These results suggest that trazodone, like the tricyclic antidepressants prolongs ventricular repolarization; but, in contrast to imipramine, it does not have anticholinergic activity.
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  • 6
    ISSN: 1432-1041
    Keywords: Propranolol ; optical isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Late plasma half-lives of dextro and racemic propranolol were measured in seven adult male subjects after 100 mg taken orally. Mean plasma half-lives of 2.38±0.43 and 2.93±0.63 h were obtained for dextro and racemic preparations respectively. In five of these subjects plasma half-lives after 50 mg dextro and laevo isomers were 2.02±0.53 and 3.20±0.42 h. No difference was found in the rates of absorption of the two isomers It is concluded that these results reflect either differences in distribution or a slower rate of metabolism of the laevo isomer.
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  • 7
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Es wird gezeigt, dass Verabreichung von Hydrallazin einen Blutdruckabfall und eine reflektorische Tachykardie zur Folge hat. Nach Praktololgabe wird eine Hemmung der reflektorischen Tachykardie erreicht, während die blutdrucksenkende Wirkung erheblich vermindert wird.
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  • 8
    ISSN: 1573-2592
    Keywords: Narcolepsy ; human leukocyte antigens ; immunoglobulin ; genetics ; restriction fragment length polymorphisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Predisposition to narcolepsy involves genetic factors both in humans and in a canine model of the disorder. In humans, narcolepsy is strongly associated with HLA DR15 and DQB1*0602. In Dobermans and Labradors, narcolepsy is transmitted as a single autosomal recessive gene with full penetrance (canarc-1). Canine narcolepsy is not linked with DLA, the canine equivalent of HLA, but cosegregates with a DNA segment with high homology with theμ immunoglobulin heavy-chain (IgH) switch-like region (Sσ). To determine if the IgH locus is involved in genetic predisposition to human narcolepsy, restriction fragment length polymorphisms specific for the IgM and IgG cluster within this locus were studied in sporadic cases of the disease, as well as in five families with two or more affected individuals. Comparisons were made between control populations and both familial and sporadic cases and for patients with and without HLA-DR15 and DQB1*0602. RFLP analysis at the Sσ andγ-1 loci, which cover over 200 kb of 14q32.3, indicates that there is no evidence for any association between the IgH region and human narcolepsy.
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