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  • 1
    Electronic Resource
    Electronic Resource
    Hepatic metabolic ability during anasthesia Evaluation of antipyrine half-lives and their relation to enflurane metabolism (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 39 (1984), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The antipyrine (phenazone) half-life was determined in 20 surgical patients to discover whether there are changes in hepatic metabolic rate during or immediately after anasthesia compared with the pre-anasthetic rate. Nine patients received enflurane (mean duration 8.6, SD 2.0 hours) and six patients had a balanced anasthetic without enflurane (duration 4.4, SD 3.3 hours). A further five patients received a spinal anasthetic with bupivacaine. The changes in antipyrine half-life were inconsistent, and there was no evidence of competitive metabolic inhibition, by general anasthesia. Antipyrine half-lives did not correlate with serum fluoride levels or urinary fluoride excretion in the case of enflurane. The mean serum inorganic fluoride concentrution rose to 29 μmol/litre, and two patients had potentially nephrotoxic concentrations (64 and 50 μmol/litre) after 8 hours of exposure to enflurane though without any evident harmful effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1984.tb06474.x
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  • 2
    Electronic Resource
    Electronic Resource
    On the mechanism of some metabolic actions of dopamine (1971)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 325-329 
    Details
    ISSN: 1432-1912
    Keywords: Dopamine ; Noradrenaline ; Hyperglycaemia ; Lipolysis ; Indirect Mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The elevation of plasma glucose, glycerol and free fatty acids following the injection of dopamine in rats was reduced after treatment with desipramine or cocaine, while similar actions of noradrenaline on these metabolic parameters were enhanced after treatment with these drugs. Since the action of dopamine was also reduced by pretreatment with reserpine, we conclude that a significant part of the metabolic effects of dopamine is mediated by an indirect mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997227
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  • 3
    Electronic Resource
    Electronic Resource
    On the cardiovascular action of dopamine in rats (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 363-371 
    Details
    ISSN: 1432-1912
    Keywords: Dopamine ; Cardiovascular Action ; Desipramine ; 6-Hydroxydopamine ; Reserpine ; Indirect Mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats anaesthetized with urethane the pressor effect of dopamine was not significantly altered by treatment with desipramine, which enhanced the action of noradrenaline on blood pressure and heart rate and abolished that of tyramine. Chemical sympathectomy with 6-hydroxydopamine in rats potentiated responses to noradrenaline and prevented the action of tyramine on blood pressure but did not significantly modify the pressor effects of dopamine. Furthermore, pretreatment with reserpine shifted the dose-response curves for dopamine and for tyramine on heart rate to the right. The dose-response curve for dopamine like that for noradrenaline on blood pressure was unaltered or shifted slightly to the left by reserpine. It is concluded that also in the rat an indirect, tyramine-like component contributes substantially to the cardiovascular action of dopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00506629
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of 6-hydroxydopamine on spontaneously hypertensive rats (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 1-13 
    Details
    ISSN: 1432-1912
    Keywords: 6-Hydroxydopamine ; Chemical Sympathectomy ; Spontaneous Hypertension ; Adrenergic Nervous System
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to evaluate the role of the sympathetic nervous system in the development and maintenance of spontaneous hypertension, spontaneously hypertensive and normotensive rats were give 6-hydroxydopamine (6-OH-dopamine). A single i.v. dose of 6-OH-dopamine (100 mg/kg) caused a biphasic rise in blood pressure in both hypertensive and normotensive rats. During long-term treatment the first dose of 6-OH-dopamine (25 or 50 mg/kg i.v.) lowered the blood pressure, measured 24 h after injection, two or three times more in hypertensive than in normotensive rats. As a result, the blood pressure reached the same level in both groups, i.e. 90–100 mm Hg. Within three days this hypotension subsided. After repeated weekly administration of 6-OH-dopamine the depressor effect declined gradually and after 4 weeks it was no longer significant. When this stage was reached, adrenal demedullation as such neither lowered the basal blood pressure, nor prevented the development of tolerance to 6-OH-dopamine. Accordingly, the adrenal medulla is not decisive in maintaining the blood pressure and in the development of tolerance to the depressor effect of 6-OH-dopamine in spontaneously hypertensive and normotensive animals. After treatment with 8 weekly doses of 6-OH-dopamine, the pressor response to noradrenaline increased in both hypertensive and normotensive rats, while the response to tyramine decreased. When, on the second day after birth, new-born rats of the hypertensive strain were given a single dose of 6-OH-dopamine (50 mg/kg i.p.) the development of hypertension was inhibited to some degree. This inhibition was more marked when the animals were given weekly doses of 6-OH-dopamine (50 mg/kg i.p.) during 5 weeks. On the other hand, when pregnant rats of the same strain received 6-OH-dopamine (50 mg/kg i.v.) twice during the last week before delivery, the offsprings did develop hypertension. It is evident that the adrenergic nervous system plays an important part in the development of hypertension in rats of a spontaneously hypertensive strain, but it is no longer of essential importance once the hypertension is established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499968
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of histamine, pentagastrin and theophylline on the production of cyclic AMP in isolated gastric tissue of the guinea pig (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 15-23 
    Details
    ISSN: 1432-1912
    Keywords: Cyclic AMP ; Gastric Secretion ; Pentagastrin ; Histamine Receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of histamine, pentagastrin and theophylline on the cyclic AMP level was studied in minced gastric tissue and isolated gastric mucosa of the guinea pig: 1. In the presence of high concentrations of minced tissue in the incubate theophylline (10−3 M), but not histamine (10−3 M), alone induced a significant elevation of the content of cyclic AMP. 2. In contrast, in the presence of low amounts of isolated gastric mucosa histamine (6×10−4 M), but not theophylline (10−3 M), alone caused an elevation of the content of cyclic AMP. 3. The combination of histamine (6×10−4 M or 10−3 M) and theophylline (10−3 M) caused a marked elevation in the level of cyclic AMP. However, the magnitude of this elevation was inversely related to the amount of tissue in the incubate. 4. The increase of the content of cyclic AMP, induced by the combination of histamine and theophylline in the isolated mucosa, was inhibited by the histamine H2-receptor antagonist burimamide, but not by the histamine H1-receptor blocking agent diphenydramine. 5. Pentagastrin alone or in combination with theophylline did not significantly change the level of cyclic AMP in the isolated tissue. The results demonstrate that the histamine-induced increase of cyclic AMP in the gastric mucosa is mediated via histamine H2-receptors, the stimulation of which is also known to increase the secretion of gastric acid. Accordingly, cyclic AMP may be the intracellular mediator of the histamine-induced secretion of gastric acid. In contrast, the pentagastrin-induced secretion of gastric acid in the guinea pig does not seem to be attributable to an increase in the level of cyclic AMP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499969
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  • 6
    Electronic Resource
    Electronic Resource
    Studies on some metabolic effects of dopa and dopamine in the rat (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 115-131 
    Details
    ISSN: 1432-1912
    Keywords: Dopamine ; l-dopa ; 6-Hydroxydopamine ; Metabolic Effects ; Adrenoceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In male rats some metabolic effects of l-dopa and dopamine were compared with those of noradrenaline, adrenaline and tyramine by measuring the changes of plasma free fatty acids (FFA), plasma glycerol and plasma glucose as well as those of blood lactate and blood pyruvate. After intravenous injection of dopamine lactate and pyruvate concentrations were elevated maximally already within 5 min and returned to control levels after 10–20 min, i.e. at a time, when the levels of FFA, glycerol and glucose were maximally elevated in plasma. l-dopa had about 1/8 to 1/6 the potency of dopamine in producing these metabolic effects. The effects of dopamine were similar to those obtained with 1/20 the dose of noradrenaline, while adrenaline produced a more pronounced hyperglycaemic response than dopamine did when given in lipolytically equieffective doses. Pretreatment of the animals with phentolamine completely prevented the hyperglycaemic response to dopamine or noradrenaline without clearcut effects on the lipolytic effect of these catecholamines. Also, pretreatment with dihydroergotamine antagonized the hyperglycaemic effect of adrenaline and prevented that of dopamine and noradrenaline, while the effect of catecholamines on plasma glycerol concentration was not affected. However, the elevation in plasma FFA level induced by catecholamines was clearly antagonized by dihydroergotamine. The β-adrenolytic drug Kö 592 had no effect on the hyperglycaemic effect of dopamine or noradrenaline, but antagonized the lipolytic effect of these amines. Pargyline enhanced the elevation of FFA and glycerol induced by dopamine or noradrenaline but reduced their hyperglycaemic effect. Chemical sympathectomy induced by pretreatment with 6-hydroxydopamine prevented the hyperglycaemic and lipolytic effects of tyramine, antagonized those of dopamine and potentiated the lipolytic response to noradrenaline. The effect of syrosingopine on the metabolic responses to the catecholamines was similar to that of 6-hydroxydopamine. Since the metabolic effects of dopamine were clearly antagonized by various α- and β-receptor-blocking agents and by chemical sympathectomy, we conclude that dopamine exerts its metabolic effects through a stimulation of α- and β-adrenoceptors and that part of this effect is mediated by a tyramine-like action of dopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501117
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 51-57 
    Details
    ISSN: 1432-1041
    Keywords: activated charcoal ; phenobarbitone ; carbamazepine ; phenylbutazone ; absorption ; elimination ; acute intoxication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of activated charcoal, given as a water suspension, on the absorption and elimination of phenobarbitone 200 mg, carbamazepine 400 mg and phenylbutazone 200 mg, was studied in five healthy volunteers, using a randomized crossover design. Absorption of the drugs was almost completely prevented (more than 95%) when charcoal 50 g was ingested within five minutes of taking the drugs. When activated charcoal was taken one hour after the drugs, the mean inhibition of drug absorption was considerably less and the inhibition was greatly dependent on the individual rate of absorption. The half-life of phenobarbitone was markedly shortened from a control value of 110±23 h to 19.8±1.0 h (P〈0.05), with a corresponding increase in plasma clearance from 4.6 ml/min to 23 ml/min, when activated charcoal 118 g, in five divided doses was given between 10 and 48 h after ingestion of the drug. The half-life of carbamazepine was shortened by 45% (P〈0.05) and the reduction in the half-life of phenylbutazone (30%) by charcoal, too, was statistically significant. The only side effect from use of the charcoal suspension was constipation, which occured in three subjects after repeated doses, and which was easily treated with lactulose if required. Although activated charcoal should be given as soon as possible, even its delayed use may be indicated, due to the slow absorption often seen in acute intoxication. The use of multiple doses of charcoal appears to be indicated as an additional treatment of certain severe intoxications to prevent the release of drugs from charcoal, and to increase their rate of elimination if they are secreted into the gut with subsequent reabsorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561677
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  • 8
    Electronic Resource
    Electronic Resource
    Comparison of activated charcoal and ipecac syrup in prevention of drug absorption (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 557-562 
    Details
    ISSN: 1432-1041
    Keywords: drug absorption ; acute intoxication ; activated charcoal ; ipecac syrup ; paracetamol ; tetracycline ; aminophylline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of activated charcoal and ipecac syrup in the prevention of drug absorption was studied in 6 healthy adult volunteers, using a randomized, cross-over design. Paracetamol 1000 mg, tetracycline 500 mg and aminophylline 350 mg were ingested on an empty stomach with 100 ml water. Then, after 5 or 30 min, the subjects ingested, either activated charcoal suspension (50 g charcoal), syrup of ipecac, or, only after 5 min, water 300 ml. Activated charcoal, given either after 5 or 30 min, significantly (p〈0.01 or 〈0.05) reduced the absorption of these 3 drugs measured, for example as AUC0–24h. Syrup of ipecac caused emesis on each occasion, with a mean delay of 15 min. When ipecac was given 5 min after the drugs, its effect on absorption was significant, but when it was given after 30 min only the absorption of tetracycline was reduced. Activated charcoal was significantly (p〈0.05) more effective than ipecac in reducing drug absorption when given at the same time points. In cases of acute intoxication, depending on the quality and quantity of the drugs ingested, the relative efficacy of charcoal and ipecac may be somewhat different from that observed in the present study. Despite its emetic action, however, ipecac syrup is not very effective in preventing drug absorption and, in general, activated charcoal should also be given after induced emesis or gastric lavage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609903
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of metformin after intravenous and oral administration to man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 195-202 
    Details
    ISSN: 1432-1041
    Keywords: metformin ; biguanides ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9±1.61 ( $$\bar X$$ ±SE), from which its elimination could be described using three-compartment open model. The elimination half-life from plasma was 1.7±0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9±0.7 h. After the intravenous dose, metformin was completely excreted unchanged in urine with a renal clearance of 454±47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50–60%. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of “flip-flop” type for oral metformin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562061
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  • 10
    Electronic Resource
    Electronic Resource
    Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 359-365 
    Details
    ISSN: 1432-1041
    Keywords: tolfenamic acid ; anti-inflammatory agent ; human pharmacokinetics ; bioavailability ; intravenous administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544587
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