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Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 109 records · Page 6Linked to original sources
PubMed1986

Major differences between lung, skin and liver in the microsomal metabolism of homologous series of resorufin and coumarin ethers.

Phenoxazone and a homologous series of its ethers (methoxy to octoxy plus benzyloxy), and coumarin and a series of its ethers (methoxy to propoxy), were metabolized by liver, lung and skin microsomes of normal adult female BALB/c mice. For each series of substrates, and with each tissue, clear structure-activity relationships were seen, relating metabolic activity to the length of the ether side-chain. With the coumarin series of substrates the structure-activity relationships were almost identical in the three tissues, with liver more active than lung and lung more active than skin. Liver, lung and skin microsomes each showed very different structure-activity relationships, however, for metabolism of the phenoxazone series of substrates. Benzyloxyphenoxazone was metabolized almost twice as fast in lung as in liver, but for the other phenoxazone substrates the activities were much greater in liver than in lung or skin. Liver, lung and skin microsomal propoxy- and benzyloxyphenoxazone dealkylase activities differed in their sensitivities to inhibition by metyrapone and alpha-naphthoflavone. The structure-activity relationship and inhibitor data for the phenoxazone substrates are consistent with a view that mouse lung and sking cyt. P-450 are predominantly similar to phenobarbitone-induced and 3-methylcholanthrene-induced forms of hepatic cyt. P-450 respectively. The results also show that the pattern of microsomal metabolism of xenobiotics in lung and skin cannot be reliably predicted from that in liver.

Animals↗
PubMed1986

Comparative efficacy of soluble aspirin and aspirin tablets in postoperative dental pain.

The efficacy of single doses (1.2 g) of soluble aspirin and aspirin tablets was determined in a randomised, placebo-controlled, double-blind, parallel study in 90 patients (45 females) with postoperative pain after removal of impacted lower third molars. Also investigated was the relationship between plasma aspirin esterase activity and overall pain scores after both aspirin preparations. Patients reported significantly less pain (p less than 0.001) after treatment with aspirin than after treatment with placebo. However, patients receiving soluble aspirin reported both an earlier onset and a longer duration of pain relief than those who received aspirin tablets. A significant correlation was observed between plasma aspirin esterase activity and overall pain scores after both soluble aspirin (r = 0.57, p less than 0.01) and aspirin tablets (r = 0.51, p less than 0.02). It is concluded that soluble aspirin is the preferred aspirin formulation for treating postoperative pain after third molar surgery and that plasma aspirin esterase activity is determinant of a patient's analgesic response to aspirin in postoperative dental pain.

Adolescent↗
PubMed1986

Activity of esterases in plasma from Ghanaian and British subjects.

We have measured aspirin esterase, cholinesterase, paraoxonase, and phenylacetate esterase activities in samples of plasma from British and Ghanaian subjects. Aspirin esterase, paraoxonase, and phenylacetate esterase activities were significantly lower in Ghanaians compared with British subjects. However, cholinesterase activities were similar in Ghanaian and British plasma samples. The lower esterase activities in Ghanaian plasma samples may result in higher circulating concentrations and greater pharmacological effects of drugs such as aspirin.

Aryldialkylphosphatase↗
PubMed1986

Ethoxyresorufin O-deethylation by human liver microsomes.

As a substrate for human liver microsomes, ethoxyresorufin appears to be metabolised by a group of cytochrome P450 isoenzymes which are inducible by cigarette smoking. Kinetic studies in microsomes from four human livers indicate that only one enzyme component is involved over the full substrate range. Ethoxyresorufin O-deethylation activity at both high and low substrate concentrations correlated with the high affinity component of ethoxycoumarin O-deethylation and of diphenyloxazole metabolism.

Adult↗
PubMed1986

Pharmacodynamics and pharmacokinetics of single doses of ketanserin and propranolol alone and in combination in healthy volunteers.

The potential interaction between ketanserin and propranolol has been investigated in eight healthy volunteers. Volunteers received single doses of placebo, propranolol (80 mg), ketanserin (20 mg), and propranolol (80 mg) plus ketanserin (20 mg) following a randomised double-blind regimen. A single dose of ketanserin had little effect on resting heart rate and blood pressure and the effects of propranolol and ketanserin in combination were similar to those of propranolol alone. The inhibition of exercise induced tachycardia by propranolol was not affected by ketanserin. The pharmacokinetics of propranolol elimination were not influenced by the concurrent administration of ketanserin, nor the pharmacokinetics of ketanserin by propranolol.

Adult↗
PubMed1986

Massive glibenclamide overdose without hypoglycaemia in a man with diabetes after partial pancreatectomy.

A 49-year-old man with non-insulin-dependent diabetes mellitus (NIDDM) from alcoholic pancreatitis took 100 mg of glibenclamide without symptoms of hypoglycaemia even when glibenclamide concentrations were high (191 micrograms/l). There was no increase in serum C-peptide concentration. The observed half-life of glibenclamide was 6 h. It is concluded that high doses of glibenclamide will not provoke pancreatic insulin secretion in NIDDM caused by pancreatic destruction, there was no evidence for an acute extra-pancreatic effect of glibenclamide and the elimination of glibenclamide may be slower than supposed previously.

Diabetes Mellitus, Type 2↗
PubMed1986

Substrate specificity of the mouse skin mixed-function oxidase system.

The metabolism of nine model substrates for the mixed-function oxidase system was studied in skin and liver microsomes from Balb/C mice. Rates of skin metabolism per mg microsomal protein ranged from 0.5-15% of liver rates depending on the substrate. Relative to liver, mouse skin preferentially metabolized ethoxyresorufin, benzo[alpha]pyrene and diphenyloxazole over aldrin, coumarin and the C1-C4 7-alkyl umbelliferone ethers. NADPH-cytochrome P-450-dependent metabolism of aldrin and ethoxyresorufin was differentially inhibited in skin microsomes by metyrapone and alpha-naphthoflavone, respectively. Biphasic Eadie-Hofstee plots were obtained in both skin and liver microsomes for the metabolism of aldrin, whereas metabolism of ethoxyresorufin in both systems was described by linear kinetics. It is concluded that mouse skin contains multiple forms of cytochrome P-450, and that forms functionally analogous to those induced by polycyclic hydrocarbons in rodent liver are present in untreated mouse skin.

Aldrin↗
PubMed1986

Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom.

The epidemiology of extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom has been studied using reports in the Adverse Reactions Register of the Committee on the Safety of Medicines (CSM) and from general practitioner prescribing data. Between 1967 and 1982 there were an estimated 37.0 million prescriptions for prochlorperazine and 3.2 million for haloperidol; in this time there were 104 reports of adverse reactions to prochlorperazine and 62 to haloperidol. The predominant extrapyramidal reaction reported was dystonia-dyskinesia (99 reports for prochlorperazine and 47 for haloperidol). The remaining reactions reported were of Parkinsonism. Dystonia-dyskinesia usually occurred within three days of commencing treatment, and for both drugs the incidence, expressed per million prescriptions, varied significantly with age, the highest incidence being in patients under 20 years. Thus young patients appear at particular risk of acute extrapyramidal reactions to dopamine receptor antagonists.

Adolescent↗
PubMed1986

Regulatory decisions and consumers.

Consumers expect regulatory authorities to evaluate the risks and benefits of non-narcotic analgesics both before marketing and throughout their marketing life. In making their evaluation, regulatory authorities attempt to ensure that before a product is marketed it is of satisfactory quality, is efficacious, tested for likely toxicological hazards and that prescribers are provided with appropriate, objective information. After marketing of a drug, regulatory authorities use spontaneous adverse drug reaction (ADR) reporting systems as their principal monitoring technique and use the data collected to help identify risk factors for human toxicity.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1985

Extrapyramidal reactions with metoclopramide.

The epidemiology of extrapyramidal reactions to metoclopramide was studied by examining reports in the Adverse Reactions Register of the Committee on the Safety of Medicines and comparing these with prescribing figures by general practitioners in the United Kingdom for metoclopramide (Maxolon). In the period 1967-82 there were an estimated 15.9 million prescriptions and 479 reports of extrapyramidal reactions (455 of dystonia-dyskinesia, 20 of parkinsonism, and four of tardive dyskinesia). When corrected for prescribing rates the relative risk of dystonia and dyskinesia was 1.8 in female compared with male patients (95% confidence interval 1.4-2.2). The overall reporting rate for dystonia and dyskinesia was 28.6/million prescriptions but was significantly more common in young adults (p less than 0.0001) and especially girls and women aged 12-19 (190.7 reports/million prescriptions). By contrast parkinsonian reactions were significantly more common in the elderly (p less than 0.0001).

Adolescent↗
PubMed1985

Which drug for the adult epileptic patient: phenytoin or valproate?

A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered.

Adolescent↗
PubMed1985

Drug acetylation and expression of lupus erythematosus.

Acetylator phenotype was measure in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls. Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D+SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators.

Acetylation↗
PubMed1985

The metabolism of 7-ethoxycoumarin in human liver microsomes and the effect of primary biliary cirrhosis: implications for studies of drug metabolism in liver disease.

Using 7-ethoxycoumarin as a probe substrate, microsomal monoxygenase activity has been measured in liver tissue from patients with primary biliary cirrhosis (PBC) of varying histological severity, and in histologically normal control tissue. Interindividual variation in enzyme activity was considerable, and in no histological category was the activity significantly different to control. We conclude that: (a) in PBC, hepatic microsomal monoxygenase activity is determined primarily by factors other than the histological severity of the liver disease, and (b) studies of xenobiotic metabolism in patients with liver disease should specify the nature of the underlying disease process.

Coumarins↗
PubMed1985

Determinants of plasma alpha 1-acid glycoprotein (AAG) concentrations in health.

The concentration of alpha 1-acid glycoprotein (AAG) was measured in plasma from 200 healthy subjects belonging to 78 family units. The AAG concentration varied markedly between individuals (mean 0.77, range 0.36-1.46 g 1(-1]. When the genetic contribution to the variability was assessed, the only significant correlation observed was that between husband and wife and this was weak. We conclude that in addition to the known effects of age and gender, environmental (rather than genetic) factors largely determine the variance of AAG concentrations.

Adolescent↗