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Biomedical subjects

F J Vajda

Publications and source records attributed to F J Vajda.

At least 55 records · Page 3Linked to original sources
PubMed1980

The principles of pharmacology.

The importance of pharmacology to the family physician needs no emphasis. The most decisive act in his approach to the patient is writing a prescription for the most appropriate drug. To achieve this, he must understand the principles underlying the use of the drugs so that by being aware of the pharmacological properties of different classes of drugs, he can make a rational choice with regard to the most appropriate drug and regime. This knowledge is essential to get maximum efficacy and the minimum of side effects.

Absorption↗
PubMed1979

Comparison of metoprolol and pindolol in the treatment of mild to moderate hypertension: a double-blind crossover study.

Matched doses of metoprolol and pindolol were administered to 31 hypertensive outpatients in a double-blind randomized crossover trial, which was designed to compare the antihypertensive efficacy and pattern of side effects of the two drugs. Twenty-nine patients completed the study. A tenfold difference in dose (25 +/- 2 mg/day of pindolol and 234 +/- 22 mg/day of metoprolol) was required to produce a similar antihypertensive effect. There was a significantly greater fall in pulse rate during metoprolol treatment. Complaints of dry mouth, mild Raynaud's phenomenon, and eye discomfort were more frequent during treatment with metoprolol; and sleep disturbances and abnormal dreaming patterns were more frequent during treatment with pindolol.

Adult↗
PubMed1979

Comparison of intravenous and oral high-dose methotrexate in treatment of solid tumours.

An outpatient regimen of oral high-dose methotrexate was studied in 14 patients with solid tumours over 12 months. Detailed pharmacokinetic analysis in five patients showed high oral bioavailability (mean +/- SE of mean 87.6 +/- 1.5%), indicating that with this regimen oral methotrexate was well absorbed and the first-pass effect low. Oral administration resulted in peak plasma methotrexate concentrations of 8.4 +/- 0.5 mumol/l (382 +/- 23 microgram/100 ml) and was almost as effective as intravenous administration, which achieved peak concentrations of 9.9 +/- 0.4 mumol/l (450 +/- 18 microgram/100 ml). In all 14 patients the clinical response to oral treatment was comparable to that reported to intravenous administration of high-dose methotrexate used in combination with other cytotoxic drugs. The disease-free interval in cases of adult sarcoma was 7.4 +/- 1.3 months and the relapse rate 29%. Out of four patients with small-cell carcinoma, two showed an objective response to oral treatment. We suggest that oral high-dose methotrexate given in divided doses is a rational alternative to expensive intravenous high-dose methotrexate regimens, but further clinical evaluation is necessary.

Administration, Oral↗
PubMed1979

Ocular side effects with 5-fluorouracil.

The concentrations of 5-fluorouracil in tears and plasma were studied in eight patients receiving the drug for carcinoma of the colon. The drug was measured by a gas liquid chromatographic method and found to be present only in the tears of patients with excessive lacrimation. In three patients with watery eyes the peak concentration in tears (16-23.8 micrograms/ml) occurred 15 minutes after IV administration and this corresponded with the end of the distribution (alpha) phase in the plasma when the plasma levels ranged from 18-26 micrograms/ml. In five patients without eye symptoms the drug was undetectable in the lacrimal fluid even though they had similar plasma levels (15-25 micrograms/ml) of 5-fluorouracil. The volumes of distribution and plasma clearance rates were similar in the two groups [being 0.2-0.52 (mean = 0.33) 1/kg and 612-978 (mean = 850) ml/min respectively in patients with excessive lacrimation and 0.13-0.79 (mean = 0.36) 1/kg and 435-1138 (mean = 831) ml/min respectively in the five patients without symptoms.]. It appears that 5-fluorouracil produces irritation of the lacrimal apparatus in about 30% of patients on the drug and in association with this appears in the tears where it may be responsible for the reported irritation and fibrosis of the tear duct.

Chromatography, Gas↗
PubMed1979

Some aspects of the clinical use of clonazepam in refractory epilepsy.

Sodium valproate and clonazepam were given in combination to 17 refractory epileptic patients and their progress was reviewed clinically and by EEG's. Even though plasma concentrations of sodium valproate and conventional anticonvulsants were monitored and adjusted according to individual requirements, combination therapy consisting of valproate and clonazepam was ineffective in controlling seizures in the majority of patients. A further 40 patients receiving clonazepam were reviewed in relation to adverse reactions. 22 patients in this group suffered from undesirable effects attributable to clonazepam. These effects were managed by cessation of the drug or a reduction in the dose. The commonest side effects were drowsiness, loss of concentration, irritability and aggression.

Adolescent↗
PubMed1978

Studies of intravenous cefoxitin (MK306).

The pharmacokinetics of cefoxitin, a new cephamycin antibiotic, were studied in six patients who were undergoing total hip replacement, and who were given cefoxitin to provide prophylactic cover at the time of operation. Later, the efficacy of cefoxitin was studied in nine patients with severe acute infections. The mean elimination phase half-life of cefoxitin which was obtained in this study (83 to 87 minutes) was significantly longer than that obtained in other studies. Cefoxitin was also found to be effective in lung and urinary tract infections against sensitive organisms. It was well tolerated, and the only side effect was that of phlebitis in long-term therapy. Cefoxitin may be valuable for prophylactic use in bowel and orthopaedic surgery.

Aged↗
PubMed1978

Sodium valproate in Huntington's disease.

The authors assessed the effect of sodium valproate, which is thought to elevate brain gamma-aminobutyric acid (GABA) levels, in the treatment of Huntington's disease by an objective ultrasound method in three patients with Huntington's disease. Despite plasma levels ranging from 47.0 to 140.8 microgram/ml (mean, 104.7), sodium valproate had no beneficial effect on involuntary movements. The authors stress the importance of activation to achieve a standard level of arousal in the assessment of involuntary movements.

Adult↗
PubMed1978

Rectal administration of sodium valproate in status epilepticus.

Six patients suffering from status epilepticus were refractory to parenteral treatment with either diazepam, amobarbital or both, and were given sodium valproate 200 to 800 mg every 6 hours. The drug was administered rectally as 200 mg lipid-based suppositories, thereby avoiding impaired absorption, which occurs in the presence of paralytic ileus. Plasma levels of sodium valproate in all patients reached the therapeutic range within 36 hours of starting therapy. Seizures were totally controlled in five patients and a 75 percent reduction was noted in the sixth. In two patients, the route of administration was changed from rectal to an equivalent oral dose with continuing control of seizures and minimal change in plasma levels, suggesting that bioavailability is similar for the two forms of the drug. The rectal route of administration was effective in achieving systemic absorption of sodium valproate in the treatment of status epilepticus.

Adolescent↗
PubMed1978

The combined use of L-alpha-methyldopa hydrazine and methyldopa in the treatment of hypertension.

1. The combined use of alpha-methyldopa and L-alpha-methyldopa hydrazine (a peripheral decarboxylase inhibitor) has been studied, in a double-blind cross-over comparison, with alpha-methyldopa and L-alpha-methyldopa hydrazine placebo in the treatment of eight patients with essential hypertension. 2. L-alpha-methyldopa hydrazine did not enhance the antihypertensive effect of alpha-methyldopa. This suggests that because methyldopa can inhibit its own decarboxylation, peripheral decarboxylation is not an important metabolic pathway for methyldopa and elevated brain levels of methyldopa do not necessarily result in elevated brain levels of methyldopamine.

Adult↗
PubMed1978

Sodium valproate: dose-plasma level relationships and interdose fluctuations.

Individual dose-plasma level relationships were studied in 14 chronically treated epileptics, 10 of whom were concomitantly receiving other anticonvulsants besides valproate. Linear regression analysis showed each individual relationship to be linear with correlation co-efficients ranging from 0.9137 to 0.9997. A considerable inter-individual variation was found to exist in the slopes of the regression lines (range: 0.86 to 5.72). This may be the consequence of differences in absorption characteristics and metabolic handling of the drug. The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient. Hourly plasma sodium valproate measurements for 6 hours between 2 successive doses, in the same group of patients, showed that the mean percentage change in post-dose peak plasma levels was 44.5%, and range from 20.7 to 153.5%. Plasma levels returned to values close to pre-dose starting levels 6 hours after the administration of a dose. The large degree of inter-dose fluctuation between doses indicates that it is preferable to use pre-dose plasma sodium valproate levels to guide the clinical management of epileptic patients.

Adolescent↗
PubMed1978

Patterns of response to levodopa in Parkinson's disease.

The broad results of the treatment of patients with idiopathic Parkinson's disease who have received levodopa or its variants are reported. 50 patients, 24 males and 26 females, with a mean age of 66.5 years were treated with levodopa, in daily doses ranging from 0.25g to 6.0g or 'Sinemet' in daily doses of 300mg to 750mg. Periods of treatment ranged from 4 months to 8 years, with a mean of 4.02 years. The relationships of patients' age, onset of Parkinsonian symptoms and interval between initial treatment with levodopa and the current clinical state were studied. Patients were classified according to their clnical response into 3 categories: satisfactory response, progressive deterioration or intolerance of levodopa. The proportion of patients in each category was 66%, 22% and 12% respectively. The clinical results of treatment correlated with those of Webster Disability Testing Scale. Analysis showed that the majority of patients tolerated levodopa and showed an initially satisfactory response. Patients who responded well were considerably younger than those who failed to respond. Patients receiving the drug for a shorter period (less than 3 years) showed a better response. After 3 years' treatment, the response declined. Patients who had had Parkinson's disease for more than 4 years appeared to do less well than those with recently diagnosed disease, but many patients responded well even when treatment was initiated 10 years after the onset of symptoms. Patients discontinued levodopa treatment because of psychoses, nausea, dyskinesia or exacerbation of urinary incontinence. The commonest side effects were nausea (34%), postural hypotension (22%), psychoses (10%) and 'on-off' phenomena in 12% of patients.

Aged↗
PubMed1977

Measurement of carbamazepine and its epoxide metabolite by high-performance liquid chromatography, and a comparison of assay techniques for the analysis of carbamazepine.

We describe a modified high-performance liquid-chromatographic method for the simultaneous analysis of carbamazepine andits biologically active metabolite, carbamazepine-10, 11-epoxide. Concentrations of both these compounds in the plasma of 35 epileptic patients receiving chronic carbamazepine therapy are presented. Concentrations of carbamazepine in plasma were related to those of carbamazepine-10, 11-epoxide (r - 0.495, P less than 0.05). Total daily doses of carbamazepine were better correlated with plasma concentrations of carbamazepine-10, 11-epoxide (r = 0.714, P less than 0.001) than of carbamazepine (r = 0.269, P greater than 0.05). Close correlations were found between results of the three assay procedures we used to measure plasma carbamazepine concentrations: high-performance liquid chromatography, gas-liquid chromatography, and enzyme immunoassay. Correlation coefficients exceeded 0.97 and regression slopes were near unity, indicating that all three procedures were individually specific for the quantification of plasma carbamazepine.

Carbamazepine↗