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Biomedical subjects

D N Bateman

Publications and source records attributed to D N Bateman.

157 records · Page 9Linked to original sources
PubMed1979

Metoclopramide and haloperidol in tardive dyskinesia.

The effect of single intravenous doses of metoclopramide (10 mg, 20 mg and 40 mg) and haloperidol (5 mg and 10 mg) have been compared to placebo (saline) in a double blind randomised study in 8 patients with tardive dyskinesia secondary to neuroleptic therapy. Tardive dyskinesia rating scores were improved significantly (P less than 0.01) 6 hours after dosing by metoclopramide 40 mg, and haloperidol 5 mg and 10 mg, when compared to placebo. Single doses of dopamine receptor blocking agents improve tardive dyskinesia. The dose of metochlopramide required to show a beneficial effect was high, and this therefore suggests that it is unlikely to be of therapeutic value as the incidence of adverse reactions would be greatly increased. By monitoring the effects of single doses of dopamine receptor blocking drugs in patients with tardive dyskinesia it is possible to compare the relative potencies of these drugs on dopaminergic systems in vivo in man.

Aged↗
PubMed1978

Pharmacokinetic and concentration-effect studies with intravenous metoclopramide.

1 Pharmacokinetic and concentration-effect studies have been carried out following intravenous injection of 10 mg metoclopramide hydrochloride to seven normal male volunteers. 2 It is proposed that a two-compartment model adequately describes the disposition of the drug which is rapidly distributed (T1/2alpha = 4.9 +/- 1.1 min) and eliminated (T1/2beta = 165.7 +/- 20.2 min). Total body plasma clearance of the drug is high (10.9 +/- 1.5 ml min-1 kg-1) and approximates to liver plasma flow. 3 Metoclopramide i.v. increases gastric emptying as measured by an ethanol absorption test (P less than 0.005). The duration of this effect is at least 3 h. 4 Ethanol given after i.v. metoclopramide administration produces significant sedation during the first hour and at 3 h (P less than 0.001). 5 The effect of metoclopramide on gastric emptying, and the degree of sedation induced by ethanol would appear to be related to plasma metoclopramide concentration. 6 Metoclopramide increases serum prolactin to 59 +/- 5.8 microgram/1 at 30 min after injection. There is a linear relationship (r = 0.809) between serum prolactin increase and plasma metoclopramide concentration.

Adult↗
PubMed1978

Treatment of the on-off syndrome in Parkinsonism with low dose bromocriptine in combination with levodopa.

The addition of bromocriptine, given in divided doses up to 30 mg per day, to conventional anti-Parkinsonism therapy has been studied in a double-blind placebo controlled clinical trial in 11 patients with Parkinsonism with the "on-off" syndrome. Four patients withdrew because of side effects. Of the seven remaining, three had clinical benefit from bromocriptine with reduction in severity and frequency of fluctuations. There was, however, no statistically significant benefit of bromocriptine when the group as a whole was assessed in terms of severity or frequency of fluctuations measured by three different methods. The mean frequency of major fluctuations on placebo was 2.9/day and on bromocriptine 1.8/day (P less than 0.1 greater than 0.05). There appears to be a limited role for bromocriptine as additional therapy in the management of some patients with the on-off syndrome.

Antiparkinson Agents↗
PubMedDate not supplied

Using the Adverse Reactions Register to study the effects of age and sex on adverse drug reactions.

Many countries maintain a register of reports of adverse reactions to drugs. Although reports are made voluntarily by doctors and dentists these registers contain much information that may be useful in pharmaco-epidemiological studies. We show how the epidemiology of adverse drug reactions (ADRs) can be studied using data from such a register, together with estimates of the numbers of prescriptions of the drug, categorized by age and sex of the patient. Reporting rates of ADRs are compared for different ages and sexes by logistic analysis, using extrapyramidal reactions to metoclopramide as an example. Highly significant effects of sex and age on reporting rates are found, with young women being most at risk. We consider possible alternative explanations of this finding, and show that relative overdosage does not account for the differences between the age and sex groups. Other possible errors in the data are also considered unlikely to alter these conclusions; these include differential bias in reporting ADRs for various age-sex groups, and errors in the prescription data. Studies based on the adverse reactions registers are useful for formulating hypotheses which can be tested in a prospective study.

Adolescent↗
PubMedDate not supplied

Clearing 'the fog on the Tyne': can the quality of therapeutics be assessed?

1. The rise in prescribing costs in developed countries is a concern for all physicians, but a particular challenge for clinical pharmacologists. 2. There are wide variations in the amounts and types of drugs prescribed in developed countries. 3. In order to address cost appropriately it is also necessary to address quality. Various aspects of the quality of therapeutics may be considered, including audit of process, patterns of prescribing of specific drugs and reporting of adverse drug reactions. 4. A consensus process is described in which primary care physicians developed criteria of prescribing quality, using data readily available within the UK. Practitioners scores using these criteria did not correlate directly with prescribing costs, indicating that cost alone cannot be used as criterion of quality. 5. The measurement of quality in therapeutics remains an important challenge for the future.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

The effect of total parenteral nutrition on hepatic drug oxidation.

Hepatic dysfunction is a frequent complication of total parenteral nutrition (TPN), indicated by derangement of standard liver function tests. However, such changes are variable and nonspecific, and represent hepatic injury rather than changes in hepatic function. Antipyrine (Phenazone) clearance is a sensitive indicator of hepatic microsomal enzyme activity and provides a more specific indication of hepatic function. This was used to investigate the effect of different TPN regimens. Patients receiving a postoperative 2000 kcal TPN regimen providing all nonprotein calories as dextrose (n = 16) showed a 34% reduction of mean antipyrine clearance after 7 days of TPN compared to controls (n = 13, p less than 0.05). This effect was seen also in patients receiving a 1600 kcal dextrose-based regimen (n = 8). In patients receiving a 2000 kcal TPN regimen in which 500 kcal were provided as lipid (n = 10), mean antipyrine clearance was not significantly different from that of the control group. This study indicates the sensitivity of hepatic microsomal oxidative function, an important route of drug metabolism, to different TPN regimens.

Antipyrine↗
PubMedDate not supplied

Clinical pharmacokinetics of metoclopramide.

Metoclopramide is rapidly and well absorbed from the gastrointestinal tract, and in man undergoes variable first-pass metabolism (oral bioavailability 32 to 100%). In man, N-4 sulphate conjugation is an important pathway of metabolism and after oral administration the ratio of free to conjugated metoclopramide in urine correlates with the plasma AUC. The elimination half-life of metoclopramide is dose-dependent after both intravenous and oral administration of single doses between 5 and 20mg. Metabolic profiles in animal species studied are very different from man. The clearance of metoclopramide is reduced in patients with renal failure to approximately 50% of normals and the terminal half-life is prolonged; this is despite the fact that renal clearance of free drug accounts for only 20% of the administered dose in normals. Preliminary studies after 'high dose' metoclopramide demonstrate accumulation to high plasma concentrations with linear kinetics, suggesting that current high dose regimens are unnecessarily cumbersome.

Aged↗
PubMedDate not supplied

Quinine amblyopia: is current management appropriate?

Thirty-one patients blind from overdoses of quinine are reported. One died from cardiotoxicity. Of the survivors, thirteen received bilateral stellate ganglion block, seven unilateral block, five a variety of other treatments aimed at increasing retinal blood flow, and five no specific treatment. Nine patients recovered vision completely but twenty were left with varying degrees of visual field constriction and one was blind at last follow-up. No treatment for oculotoxicity was of benefit. Since experimental and clinical observations show that the primary toxic effect of quinine is on photoreceptor cells, stellate ganglion block and other vasodilator treatments have no rational basis and should no longer be recommended.

Amblyopia↗