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Biomedical subjects

M Dam

Publications and source records attributed to M Dam.

At least 145 records · Page 8Linked to original sources
PubMed1980

Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man.

Interactions between analgesics and anti-epileptic drugs may sometimes present a serious clinical problem. The aim of the study was to investigate the influence of usually applied doses of dextropropoxyphene (DPX) on the steady state levels of carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB). Sixteen patients in monotherapy completed the trial, while four patients dropped out. In patients on CBZ serum levels increased (mean appr. 66%) after 6 days on DPX. In three of the patients a further increase was seen after an additional week on DPX. One patient discontinued the DPX intake because of clinical signs of toxicity, but the remainder were clinically unaffected. CBZ-epoxide levels declined simultaneously. For DPH only a doubtful increase was observed after 1-2 weeks on DPX. For PB an average increase of 20% in serum level was noted after 1 week. The protein binding of CBZ and DPH was not affected. It is concluded that patients on CBZ should be treated only with DPX if monitored properly. Patients on DPH or PB should be followed carefully until further evidence has been produced.

Adolescent↗
PubMed1979

Carbamazepine vs phenytoin. A controlled clinical trial in focal motor and generalized epilepsy.

The antiepileptic effects of carbamazepine and phenytoin were compared in a double-blind crossover trial studying patients with primary and secondary generalized seizures and partial seizures with motor symptoms. Each treatment period lasted ten weeks. The patients were seen every two weeks, and doses were adjusted according to plasma levels. It was attempted to keep levels in the optimal plasma range, ie, 10 to 20 and 4 to 10 mg/liter for phenytoin and carbamazepine, respectively. Twenty-three patients entered and 19 completed the study. No statistically significant differences were found between carbamazepine and phenytoin with regard to seizure control and acute side effects.

Adolescent↗
PubMed1977

Interaction between carbamazepine and propoxyphene in man.

This investigation was carried out because of a clinical suspicion of drug interaction between Propoxyphene (PRX) hydrochloride and Carbamazepine (CBZ). Seven out-patients, six suffering from epilepsy and one from trigeminal neuralgia, treated with CBZ alone or in combination with phenobarbitone, received PRX hydrochloride capsules, 65 mg three times a day. Two patients stopped the PRX intake after 2 days due to severe side effects. Three of the remaining patients had symptoms and signs of drug intoxication. Blood samples were examined by thin-layer chromatography. A marked increase (45-77 per cent) in CBZ plasma level was found in all patients on combined treatment of CBZ and PRX. There were no significant changes in CBZ-10,11-epoxide level. The results suggest an inhibition of CBZ metabolism when CBZ and PRX are administered simultaneously.

Adolescent↗
PubMed1976

Multiple sclerosis. The value of clinical vestibular examination.

A clinical vestibular examination was carried out on 82 patients with multiple sclerosis (MS) selected on McAlpine's criteria. Spontaneous nystagmus, positional nystagmus or pathological caloric test were found in 49 (60%) patients. Pathological horizontal optokinetic nystagmus occurred in 47 (57%) patients. In 36 cases horizontal optokinetic nystagmus was pathological to both sides, in 28 cases combined with a pathological vertical optokinetic nystagmus, indicative of diffuse intracerebral lesions. Lesions in the central vestibular system and in the optokinetic pathways were frequently discovered in early or atypical cases of MS.

Adult↗
PubMed1976

Diazepam: intravenous infusion in the treatment of status epilepticus.

As the anticonvulsant plasma level of diazepam (DZP) after intravenous injection is maintained only for a short period, it is profitable to administer DZP as an intravenous infusion. It has, however, been claimed that DZP cannot be mixed with dextrose injection as DZP would precipitate. As this is in contrast to our clinical experience we added DZP of various brands to dextrose injections. A precipitate was in fact found in dextrose injections containing Valium and Stesolid whereas Diazepam A.L. was not only slightly cloudy. The concentration of DZP was, however, the same in all the samples and corresponded to the calculated concentration. The precipitate in the solutions with Valium and Stesolid which did not pass the filter must therefore be due to additives, most probably benzoates. On the basis of these findings and our clinical experience of this mode of administration we recommend the infusion method as one of the most effective in the acute treatment of status epilepticus.

Benzoates↗
PubMed1976

Clinical pharmacokinetics of anticonvulsants.

Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies. The most important advantage is that the frequent interindividual variation in the plasma level/dose ratio for these drugs can be circumvented by plasma level monitoring. For several anticonvulsants the brain concentration is shown to parallel the plasma concentration. Phenytoin (diphenylhydantoin) is stil the most important anticonvulsant and the one for which kinetics have been thoroughly investigated in man. These investigations have revealed several reasons for the wellknown difficulties in using this drug clinically. The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose. The elimination capacity is saturable causing dose dependent kinetics, which again means disproportional changes in plasma level with changes in dose. Great individual variations exist in the rate of metabolism, and several pharmacokinetic drug interactions are known. As an optimum therapeutic plasma concentration range has been established monitoring plasma levels must be strongly advocated. Interpretation of plasma levels in uraemic patients must take into account decreased protein binding of the drug. Carbamazepine is probably as effective as phenytoin. The elimination is a first order process, but the rate of metabolism increases after a few weeks' treatment. An active metabolite (epoxide) may be the cause of some side-effects. Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary. An optimum therapeutic concentration range has been suggested and plasma monitoring is advocated, along with that of the active metabolite, the epoxide. Phenobarbitone is still much used but its kinetics have been investigated to a lesser extent. The main problem is the variability in the rate of elimination. In children the half-life of phenobarbitone is only half of that in adults. An optimum therapeutic plasma range has been established and monitoring is recommended. Primidone may have an anticonvulsant activity in itself, but its main metabolite is phenobarbitone. The relatively rapid elimination of primidone is offset by the long half-life of phenobarbitone. An optimum therapeutic range has been suggested, but plasma level monitoring must include determination of phenobarbitone. Ethosuximide. The clinical pharmacokinetics of this important petit mal anticonvulsant is not well known. It has a relatively long half-life (in adults 2 to 3 days; in children shorter). An optimum therapeutic range has been suggested, and routine monitoring of plasma levels may be recommended. Diazepam exerts a repid anticonvulsant activity when the plasma concentration exceeds approximately 500ng/ml after intravenous injection. The kinetic pattern is complex in man. Clonazepam. The clinical pharmacokinetics are still not fully investigated but a therapeutic range has been suggested...

Administration, Oral↗