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  • 1
    Electronic Resource
    Electronic Resource
    PREGNANCY AND THE ACUTE PORPHYRIAS (1977)
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 84 (1977), S. 0 
    Details
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: An analysis is presented of the obstetric histories of 50 women with acute porphyria, comprising 39 with acute intermittent porphyria, 3 with variegate porphyria and 8 with hereditary coproporphyria. Fifty-four per cent of the women with acute intermittent porphyria had an acute attack of porphyria in pregnancy and/or the puerperium. Only one maternal death was recorded. One patient with variegate porphyria and two with hereditary coproporphyria had an attack related to pregnancy. The total fetal wastage was 13 per cent. The babies born to mothers with acute intermittent porphyria, who experienced an acute attack during pregnancy, were smaller than those in which no such attack occurred (P〈0·001). In 13 non-porphyric primigravidae there was a rise in urinary excretion of 8-aminolaevulinic acid, porphobilinogen and coproporphyrin up to the 28th week of gestation. It is probable that pregnancy has some deleterious effects in acute porphyria but the prognosis of the porphyric pregnancy is much better than the literature suggests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-0528.1977.tb12480.x
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  • 2
    Electronic Resource
    Electronic Resource
    Inhaled fentanyl as a method of analgesia (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 45 (1990), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A study was undertaken to investigate the use of fentanyl by aerosol for postoperative analgesia. Seven patients had placebo, six received fentanyl 100 μg and seven were given fentanyl 300 μg. A significant improvement in postoperative pain, as assessed by linear visual analogue scale, was achieved in the higher dose group, and in both fentanyl groups the time to alternative analgesia was significantly longer than in the control group. Serum fentanyl levels after inhalation of 100 μg reached a plateau around 0.04 ng/ml and after 300 μg at around 0.1 ng/ml after 15 minutes. Inhaled fentanyl may have a useful analgesic effect despite these low serum levels; this supports the hypothesis that the mode of analgesia from inhaled opioids may be different from that after other routes of administration. There were no adverse effects such as respiratory depression, bronchospasm, nausea or drowsiness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1990.tb14331.x
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of verapamil on the pharmacokinetics of adriamycin (1986)
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. 239-242 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The concurrent administration of adriamycin (intravenous) and verpamil (oral) is of considerable interest because of experimental data suggesting that resistance to adriamycin may be overcome by this means. The potential for a pharmacokinetic interaction between the two drugs has therefore been investigated in five patients with small cell lung cancer treated with combination chemotherapy comprising adriamycin, VP16, vincristine and cyclophosphamide. The data indicate that a significant interaction takes place. Adriamycin peak levels, terminal halflife and the volume of distribution at steady state are higher, whereas plasma drug clearance and the volume of the central compartment are lower with co-administration of verapamil. There was no evidence of enhanced drug toxicity in this study; however, the data should be considered in the interpretation of clinical trials in which adriamycin and verapamil are used together, both in terms of toxicity and tumour response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273394
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  • 4
    Electronic Resource
    Electronic Resource
    Sedation in intensive care: morphine and renal function (1986)
    Springer
    Intensive care medicine 12 (1986), S. 359-365 
    Details
    ISSN: 1432-1238
    Keywords: Sedation ; Morphine ; Renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous morphine infusions have been administered to 12 critically-ill patients during controlled ventilation. Acute oliguric renal failure was present in 4 patients, who were treated with a combination of haemofiltration and haemodialysis. Severity of physiological disturbance was assessed using a modified APACHE Score, level of sedation by a linear-analogue scale, and blood morphine levels by high-pressure liquid chromatography. Morphine clearance was impaired in renal failure, and was dependent on haemofiltration volumes; accumulation of morphine did not occur during this form of treatment. Conscious level was clearly more closely related to the degree of physiological disturbance than blood morphine levels; and for a given blood morphine level, depression of consciousness was more pronounced the greater the degree of physiological disturbance. Use of a physiological sickness score may help to clarify some of the factors influencing cerebral function during critical illness. Careful clinical monitoring of level of sedation is important in patients with oliguric renal failure receiving morphine, and haemofiltration appears to reduce the risk of morphine accumulation in these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00292926
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  • 5
    Electronic Resource
    Electronic Resource
    Decreased drug binding in serum from patients with chronic hepatic disease (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 429-432 
    Details
    ISSN: 1432-1041
    Keywords: Drug-protein binding ; hepatic disease ; salicylate ; sulphadiazine ; phenylbutazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The binding of 3 drugs to serum proteins of patients with chronic hepatic disease has been studied by an ultrafiltration technique, and compared to that of normal subjects. The binding of phenylbutazone was reduced in all patients, salicylate in patients with inactive liver disease and sulphadiazine in patients whose disease was active. Analysis of binding data showed a real reduction in the capacity of albumin to bind the drugs in the majority of patients. Addition of bilirubin to normal plasma caused a reduction in sulphadiazine binding, but had no effect on the binding of salicylate or phenylbutazone. The possible causes of this reduction in binding are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606560
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  • 6
    Electronic Resource
    Electronic Resource
    Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 605-611 
    Details
    ISSN: 1432-1041
    Keywords: oxprenolol ; hypertension ; osmotic delivery system ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615225
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  • 7
    Electronic Resource
    Electronic Resource
    The effects of chronic carbamazepine treatment on haem biosynthesis in man and rat (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 241-247 
    Details
    ISSN: 1432-1041
    Keywords: carbamazepine ; porphyria ; epilepsy ; haem biosynthesis ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p〈0.001) and ALA-dehydratase activity was reduced by 37% (p〈0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (r s=−0.45;p〈0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (bothp〈0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558260
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  • 8
    Electronic Resource
    Electronic Resource
    Controlled evaluation of a supplementary dose of carbamazepine on psychomotor function in epileptic patients (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 195-199 
    Details
    ISSN: 1432-1041
    Keywords: carbamazepine ; epilepsy ; anticonvulants ; psychomotor function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an additional dose of 400 mg carbamazepine (CBZ) on a series of simple psychomotor tests was investigated in 8 patients with epilepsy receiving chronic CBZ monotherapy in a balanced randomised double-blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free CBZ and CBZ 10,11 epoxide (CBZ-E) concentrations were performed at 10, 12, 14, 16 and 18 h after the extra dose which was administered at 23.00 h on the previous evening. The CBZ increment produced significant impairment of (i) choice reaction recognition time from 10–16 h after the dose (ii) total choice reaction time at 12 h (iii) card sorting at 12 h (iv) sedation scoring at 12 h. No significant effect on critical flicker fusion threshold, finger tapping or simple memory testing was noted. No patient reported increased side-effects in the placebo phase while 5 noted new symptoms likely to be attributable to the additional CBZ. Areas under the concentration-time curves from 10–18 h were higher following CBZ than placebo for total and free CBZ and CBZ-E concentrations. This study has demonstrated decrements in performance of a series of simple psychomotor tests in epileptic patients receiving a supplemental CBZ dose. Patients with epilepsy who require high CBZ concentrations for optimal control of seizures may be at risk of concurrent impairment of psychomotor function. Simple objective measures of performance may help in assessing the benefit-risk ratio.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606658
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  • 9
    Electronic Resource
    Electronic Resource
    Increased peritoneal permeability in patients with peritonitis undergoing continuous ambulatory peritoneal dialysis (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 187-191 
    Details
    ISSN: 1432-1041
    Keywords: cefuroxime ; peritonitis ; peritoneal dialysis ; toxicity ; increased permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The distribution of cefuroxime (250 mg) was studied in patients with renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD). 10 uninfected patients received the drug intravenously and intraperitoneally, while 9 patients with peritonitis were randomly allocated to intravenous or intraperitoneal administration. Samples were taken over the first 6 hour dialysis period. In the infected patients, more drug (p〈0.01) crossed into the peritoneal cavity following intravenous injection and reached the systemic circulation following intraperitoneal administration than in the uninfected group. This increased permeability of the peritoneal membrane during infection may result in unexpected systemic toxicity in patients treated with intraperitoneal antibiotics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609690
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  • 10
    Electronic Resource
    Electronic Resource
    Differential induction of antipyrine metabolism by rifampicin (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 155-160 
    Details
    ISSN: 1432-1041
    Keywords: rifampicin ; antipyrine ; 3-hydroxymethylantipyrine ; 4-hydroxyantipyrine ; norphenazone ; cytochrome P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8±0.9 ml/min to 13.3±1.3 ml/min, to norphenazone from 5.8±0.6 ml/min to 19.3±2.1 ml/min and to 4-hydroxyantipyrine from 14.3±2.2 ml/min to 21.9±3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637517
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