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Biomedical subjects

D N Bateman

Publications and source records attributed to D N Bateman.

At least 19 recordsLinked to original sources
PubMed1992

Mutant debrisoquine hydroxylation genes in Parkinson's disease.

The frequency of fifteen genotypes of CYP2D6 (debrisoquine 4-hydroxylase) in 53 patients with Parkinson's disease was determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses and compared with the findings in 72 healthy controls. The commonest mutant allele, CYP2D6B, was twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.70 (95% confidence interval 1.14-6.41; p = 0.0063) for subjects homozygous or heterozygous for this allele.

Aged↗
PubMed1992

The pharmacokinetics and effects of prochlorperazine in elderly female volunteers.

The pharmacokinetics and effects of prochlorperazine (PCZ) have been studied in six healthy elderly female volunteers in a double-blind placebo-controlled study of 3.125 mg intravenous (IV) and 25 mg oral PCZ. The pharmacokinetics of IV PCZ in elderly subjects appear similar to those previously obtained in young subjects, with a terminal half-life of 7.5 +/- 1.8 h after intravenous dosing. Oral bioavailability was low (14.7 +/- 1.5%). The pharmacological actions of prochlorperazine in elderly people appear to include antidopaminergic (prolactin rise) and anticholinergic (reduced salivary flow) effects. At the dose of PCZ used in this study, no significant haemodynamic or psychomotor changes were observed though there was a trend to prolongation of the movement component of the reaction time.

Administration, Oral↗
PubMed1992

Pharmacokinetic optimisation of antiemetic therapy.

Antiemetic drugs are used to treat nausea and vomiting due to a variety of causes and have a wide range of pharmacological properties. The choice of drug will, therefore, depend in part on the condition being treated. The drugs can be classified as dopamine antagonists (including phenothiazines and nonphenothiazines), corticosteroids, cannabinoids, benzodiazepines, serotonin antagonists, antihistamines and anticholinergics. There is very little evidence of a relationship between plasma drug concentrations and either their efficacy or the incidence of adverse effects with most antiemetic drugs. With drugs for which concentration-effect studies have been performed, e.g. the benzodiazepines and antihistamines, the effects monitored have not been directly relevant to their use as antiemetics. Antiemetics are used widely, for example, in cancer chemotherapy. Nonetheless, apart from metoclopramide, little work has been done on the influence of indicators of systemic disease on the pharmacokinetics of antiemetic drugs.

Adrenal Cortex Hormones↗
PubMed1992

Attitudes to adverse drug reaction reporting in the Northern Region.

1. The attitudes and knowledge of doctors in the Northern Region to reporting of adverse drug reactions were assessed using a postal questionnaire to all doctors in two, previously identified, high reporting and two low reporting health districts. Comparisons were made of the attitudes and knowledge within professional groups (GPs, Consultants and Junior Hospital Doctors), and between the amalgamated doctor groups. 2. 1181 of 1600 doctors (74%) responded. Despite being selected on the basis of previous adverse drug reaction reporting patterns, GPs and consultants from high and low reporting districts perceived they had sent a similar number of ADR reports, and there were few differences in opinion and attitude within these two groups. 3. Most differences within doctor groups were found for junior doctors, with those from low reporting districts indicating they had sent significantly less yellow cards than those in high reporting districts. There were also significant differences in the estimates junior doctors made with a frequency of adverse drug reactions, the existing documentation on adverse drug reactions, and the purposes of the adverse reaction scheme. 4. General Practitioners in low reporting areas stated they wrote more prescriptions (P < 0.02), consultants spent more time in clinical contact (P < 0.01) and junior doctors did both (P < 0.01), all of which suggest different workloads may effect reporting of adverse drug reactions. 5. When given clinical examples, or asked about the CSMs black triangle scheme, all doctor groups performed poorly. 6. The number of reports stated as being sent increased with time from qualification for 10 years, then seemed to plateau.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients.

Nine elderly parkinsonian volunteers took single doses of 384 mg of chlormethiazole, 10 mg of temazepam and placebo capsules in a double-blind three-way cross-over study on separate visits at least one week apart. In the 6 hours following the dose, the level of drowsiness, performance on a series of psychomotor tests, effects on parkinsonian symptoms and signs, and standing and lying blood pressure were recorded. Chlormethiazole produced drowsiness on all tests and impaired psychomotor performance, as compared with placebo, without affecting parkinsonian symptoms and signs, or postural blood pressure. Temazepam was consistently less potent than chlormethiazole on tests of drowsiness and psychomotor performance. Both treatments were well tolerated. It is suggested that chlormethiazole is safe to use as a hypnotic at this dosage in this group of patients with Parkinson's disease, while temazepam did not appear to be effective as a hypnotic at this dosage.

Aged↗
PubMed1991

Geographical differences in adverse drug reaction reporting rates in the Northern Region.

The reporting rates of adverse drug reactions in the Northern Region have been examined with respect to source (hospital or general practice) and district of origin for the 3 years 1986-88. Mean annual reporting rates, corrected for population, or clinical activity, varied approximately 4-fold in general practice (0.066 to 0.257 reports per 1000 resident population) and more than 12-fold in hospitals (0.14 to 1.77 reports per 1000 deaths and discharges). There was no correlation between hospital and general practice reporting rates in the same health district. Overall more reports were received from general practice (1606) than hospitals (1000), although proportionally more reports of serious adverse reactions originated from hospitals. The reasons for these differences are unclear.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1991

Clinical pharmacology of prochlorperazine in healthy young males.

1. The pharmacokinetics and pharmacodynamics of prochlorperazine (PCZ) have been studied in healthy young males following single 12.5 mg i.v. and 50 mg oral doses, and during repeated doses (25 mg twice daily) for 14 days. 2. Oral bioavailability was low and an N-desmethyl metabolite was detected. Plasma clearance was high (0.98 1 kg-1 h) and the volume of distribution was large (12.9 1 kg-1) after i.v. dosing. 3. The terminal elimination half-life of PCZ was 9 +/- 1 h and 8 +/- 2 h after i.v. and single oral dosing, respectively. The urinary recoveries of drug and metabolite were low. 4. Accumulation of PCZ and its metabolite occurred following repeated dosing. The half-life at the end of 14 days therapy was 18 +/- 4 h. 5. Postural tachycardia, decreased salivary flow, impaired psychomotor function and a diminished level of arousal were observed after intravenous PCZ. Similar effects, but of lower magnitude were observed after single oral doses. During chronic dosing postural tachycardia and antihistaminic effects were observed, the latter not being observed after single doses. 6. After single intravenous dosing the maximal drug effects occurred 2-4 h after peak plasma drug concentrations for all measures except for plasma prolactin and self-scored restlessness 7. An antagonist action at dopamine (D2), muscarinic-cholinergic and alpha-adrenoceptors is postulated after single doses, with antihistaminic effects during chronic dosing, possibly indicating the presence of an active metabolite.

Administration, Oral↗
PubMed1990

Effect of mefenamic acid on bowel transit time in healthy adult volunteers.

The effect of mefenamic acid on bowel transit time was investigated. Seven healthy adult male subjects of age 39 +/- 2.4 years (mean +/- S.E.M.) received placebo or mefenamic acid (500 mg t.d.s) orally in randomized order for five days, with a 7-day washout between studies. On the third morning after starting the drug they had a meal containing Redi-Brek and baked beans with radio-opaque markers. Small bowel transit time was measured using breath hydrogen, and whole gut transit time was measured using radio-opaque markers. The small bowel transit times were 160 min (median) with placebo and 50 min with mefenamic acid (P less than 0.05). The percentages of appearance of marker in stool within 24 h were 24.9 +/- 11.8 (mean +/- S.E.M.) with placebo and 48.9 +/- 11.7 with mefenamic acid (P less than 0.05). The times of appearance of twenty-fifth marker in stool were 41.0 +/- 4.4 h with placebo and 26.9 +/- 3.2 h with mefenamic acid (P less than 0.05). The total weights of faeces in 72 h were 500.9 +/- 96.2 g with placebo and 657.1 +/- 118.8 g with mefenamic acid (P less than 0.05). Mefenamic acid in therapeutic doses (500 mg t.d.s.) accelerated bowel transit time in healthy subjects.

Adult↗
PubMed1990

Effect of intravenous atropine on gastric emptying, paracetamol absorption, salivary flow and heart rate in young and fit elderly volunteers.

1. The effects of atropine on gastric emptying, paracetamol absorption, salivary flow and heart rate were examined in young and elderly subjects. 2. Seven healthy young male subjects of age 23 +/- 1.3 years (mean +/- s.e. mean) and seven fit elderly subjects of age 70 +/- 1.6 years received placebo (P), 300 micrograms atropine (A300) or 600 micrograms atropine (A600) in randomized order at weekly intervals. After 10 min they ingested a 500 ml orange drink containing 1 g paracetamol. Gastric emptying was measured by ultrasound, blood samples were taken to measure plasma paracetamol concentration by h.p.l.c., salivary flow was measured by dental cotton wool cylinder technique and pulse rate was recorded. 3. In young subjects, the gastric 5 min volumes were 260.1 +/- 17.9 ml (s.e. mean) with P, 310.6 +/- 10.5 ml with A300 and 317.9 +/- 8.9 ml with A600. In elderly subjects, the gastric 5 min volumes were 166.7 +/- 10.1 ml with P, 252.6 +/- 13.7 ml with A300 and 266.0 +/- 14.8 ml with A600. Thus the early adaptive phase of gastric emptying was more rapid in the elderly than the young with all treatments (P less than 0.05). The gastric emptying half-lives were 18.8 +/- 2.5 min with P, 30.0 +/- 2.7 min with A300 and 34.5 +/- 3.3 min with A600 in young subjects (P less than 0.01). In elderly subjects, the gastric emptying half-lives were 16.1 +/- 2.5 min with P, 23.7 +/- 2.4 min with A300 and 30.0 +/- 2.9 min with A600 (P less than 0.01). Thus atropine intravenously in therapeutic dose (300 and 600 micrograms) delayed gastric emptying in both young and elderly subjects. The inhibitory effect of atropine on the early adaptive phase of gastric emptying appeared to be greater in the elderly. The maximum plasma concentration (Cmax) of paracetamol was greater in the elderly than young with all treatments (P less than 0.05). There was a close relationship between the early adaptive phase of gastric emptying and paracetamol absorption (P less than 0.05). Atropine reduced salivary flow and increased resting heart rate in both young and old subjects. The effect of atropine on salivary flow was greater in the elderly. 4. The dose-response relationship varied in the three systems (stomach, salivary glands and heart rate) studied. Age had an effect on the magnitude of the response, but not on the slope of the dose-response curve for the two doses of atropine studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗
PubMed1990

The effect of pharmacological modification of gastric emptying and mouth-to-caecum transit time on the absorption of sugar probe marker molecules of intestinal permeability in normal man.

The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32-44 years, received saline, 600 micrograms atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3-O-methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l-1 and the dose administered was 80 ml m-2 body surface area. Gastric emptying was measured by ultrasound, mouth-to-caecum transit time by breath hydrogen analysis and sugar concentrations by gas-liquid chromatography. Gastric emptying half-times (min) were [mean (95% confidence intervals)] 14.9 (11:4-18.5) after saline, 22 (18.7-25.2) after atropine and 10.3 (7.0-12.6) after metoclopramide (P less than 0.002). Transit times (min) were 68.9 (52-85.2) after saline, 143 (126-159) after atropine and 38 (21.2-54.5) after metoclopramide; P less than 0.0001. Analysis of plasma levels of mannitol and 3-O-methyl glucose showed a significant within-subject effect of drug with time (P less than 0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974-1620) mg after saline, 1560 (1210-2013) mg after atropine and 955 (740-1232) mg after metoclopramide (P less than 0.03). There were no significant differences in lactulose and 3-O-methyl glucose urinary excretion between drug treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pharmacokinetics and toxic effects of nifedipine in massive overdose.

A 57-year-old man took 30 x 20 mg nifedipine retarded release tablets. He developed hypotension, tachycardia and flushing, but remained in sinus rhythm. The concentration of nifedipine 10 h after overdose was 604 micrograms 1-1, and of the M-I metabolite 110 micrograms 1-1. Log concentration time curves were linear from 10-72 h for nifedipine, with a half-life of 7.5 h; and for M-I with a half-life of 8.2 h. On this evidence, oral absorption of nifedipine retarded release is complete by 10 h. There was no evidence of saturation of nifedipine or M-I metabolism, even at concentrations ten times above the therapeutic concentration.

Drug Overdose↗
PubMed1989

Age and the pharmacokinetics of morphine.

Eight healthy young and nine healthy elderly volunteers received 10 mg morphine sulphate as an intravenous infusion, an oral solution and a slow-release tablet (MST Continus, Napp Laboratories) on three separate occasions. Pharmacokinetic profiles of morphine base were measured over a 24-h period using 13 sampling times. The elderly group showed decreased morphine clearance with a trend to a smaller volume of distribution. They achieved higher maximum plasma concentrations (Cmax) after both oral formulations and had larger areas under the plasma concentration-time curves. The times to reach maximum concentrations were the same in both groups for all formulations.

Administration, Oral↗
PubMed1989

Cyclosporine-associated hypertension in cardiopulmonary transplantation. The beneficial effect of nifedipine on renal function.

In a retrospective review of fifty heart, lung, and heart-lung recipients receiving cyclosporine, forty-six (92%) were hypertensive. This hypertension was managed with either prazosin (n = 29) or nifedipine (n = 17). Renal function was assessed by creatinine clearance estimation and found to be significantly better in those patients receiving nifedipine. (creatinine clearance = 60 ml/min [SEM 5.7] vs. 49 ml/min [SEM 2.7]; P less than 0.05). This observation suggests that nifedipine should be the drug of choice for the treatment of cyclosporine-associated hypertension in cardiac and pulmonary transplant recipients.

Adult↗
PubMed1989

Effect of oral activated charcoal on quinine elimination.

The effect of repeated dose oral activated charcoal on quinine elimination has been studied following a therapeutic (600 mg) dose of quinine bisulphate to seven normal volunteers. Activated charcoal lowered quinine half-life from 8.23 +/- 0.57 s.d. h to 4.55 +/- 0.15 s.d. h (P less than 0.001) and increased its oral clearance by 56%. Activated charcoal may have a role in the management of quinine poisoning.

Administration, Oral↗
PubMed1989

Pharmacokinetics and toxic effects of diltiazem in massive overdose.

A 50-year-old man with ischaemic heart disease took 98 tablets of diltiazem 60 mg with alcohol. He developed a junctional bradycardia, hypotension and reduced cardiac function refractory to intravenous calcium gluconate. He survived with temporary cardiac pacing and infusion of dopamine. As much as half the dose was vomited back, but nonetheless the plasma diltiazem concentration reached 6090 micrograms/l before falling mono-exponentially with a half-life of 8.6 h. Sinus rhythm returned when the plasma concentration of diltiazem was around 750 micrograms/l. Standard resuscitative procedures sufficed to treat massive diltiazem overdosage.

Adult↗
PubMed1989

Extrapyramidal reactions to metoclopramide and prochlorperazine.

We have investigated prospectively the incidence of extrapyramidal events amongst patients receiving 'first' prescriptions for metoclopramide (n = 2557) and prochlorperazine (n = 2811) from general practitioners in the Northern Region using community pharmacists to capture prescriptions. There were 12 reports of acute dystonic-dyskinetic events following metoclopramide and the incidence of this reaction was significantly greater in those under 30 years than in those 30 years and over. Following prochlorperazine there were eight reports of Parkinsonism in patients whose ages were known; seven were over 60 years. The incidence in those over 60 years was significantly higher than in those less than 60 years.

Adolescent↗