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Biomedical subjects

L F Prescott

Publications and source records attributed to L F Prescott.

At least 55 records · Page 3Linked to original sources
PubMed1988

Reduced felodipine bioavailability in patients taking anticonvulsants.

Felodipine is a dihydropyridine calcium antagonist, structurally related to nifedipine, which undergoes extensive first-pass hepatic metabolism and normally has an oral bioavailability of 15%. Felodipine disposition was studied in 10 patients who had microsomal enzyme induction due to chronic anticonvulsant therapy, and in 12 normal volunteers matched for age and sex. Plasma felodipine concentrations after a 5 mg oral dose were grossly reduced in the epileptic patients: the mean peak concentration was 1.6 (vs 8.9) nmol/l, and the area under the curve was only 2.0 (vs 30.0) nmol.h/l. The relative bioavailability of felodipine in the epileptic patients was thus only 6.6% of that in the normal subjects, and less than 1% of the oral dose was systemically available. Patients on anticonvulsant treatment will require substantially higher doses of felodipine to achieve plasma concentrations equivalent to those in non-induced subjects.

Administration, Oral↗
PubMed1988

The toxic effects of alpha-chloralose.

1. Alpha-chloralose, formed by the condensation of glucose with chloral, is used as a rodenticide and in the control of bird pests. 2. In two cases of poisoning with alpha-chloralose the clinical features included coma and generalized convulsions resembling the effects of strychnine more than those of chloral hydrate. 3. The principles of management are the support of vital functions in the unconscious patient and removal of unabsorbed poison by gastric lavage. Diazepam may be used to control convulsions.

Adolescent↗
PubMed1987

Who needs molar units for drugs?

The standardisation of units for drug concentration measurement in clinical medicine is an urgent necessity. The obvious choice is mass units based on the litre. A change to molar units for drug concentrations would make no sense unless drugs were also prescribed in moles, which would cause disruption and inconvenience. There would be considerable danger to patients and the change would be expensive. Most importantly, molar units for drugs will not benefit doctors or their patients. Mass units should be retained and proposals for the adoption of molar units should be abandoned.

Humans↗
PubMed1987

Haemodialysis for paraquat poisoning.

Paraquat can be removed by haemodialysis and haemoperfusion but, although clearance values are high, the quantities recovered are insignificant. Prevention of death is most unlikely except perhaps in patients with plasma paraquat concentrations very close to the previously proposed line separating concentrations in fatal cases and survivors at different time intervals. Even if delays incurred in measuring plasma paraquat concentrations and in setting up haemodialysis or haemoperfusion could be reduced to a minimum, elimination by these procedures would achieve little because paraquat disappears rapidly from the plasma in the first few hours after ingestion as it is taken up by the tissues and excreted into the urine. Further studies on patients at borderline risk are required and the value of 'continuous' haemoperfusion requires further assessment.

Adult↗
PubMed1987

Changes in cardiorespiratory function during gastric lavage for drug overdose.

Cardiorespiratory function in 42 patients admitted to the Regional Poisoning Treatment Centre, Edinburgh who underwent gastric lavage for self poisoning, was studied using an electrocardiograph and an ear oximeter. Mean pulse rate rose from 92 to 121 beats per min and the mean partial pressure of oxygen fell from 95 to 80 mmHg during lavage (P less than 0.001). These changes were significantly greater in conscious than unconscious patients, in smokers than in non-smokers and most marked in male smokers aged 45 or older. No sex or age differences were noted. Electrocardiograph changes were noted in 41% of patients, including potentially serious changes in 2 patients. The indications for gastric lavage should probably be reviewed particularly in conscious older patients who smoke and due consideration given to induced emesis and ingestion of activated charcoal as alternatives.

Adolescent↗
PubMed1987

Self-poisoning and therapeutic intoxication with lithium.

Of 68 admissions for lithium overdose over 16 years, 25 were due to therapeutic intoxication and 43 to deliberate self-poisoning. Three patients with therapeutic intoxication had acute diabetes insipidus with hypernatraemia. One of them had acute renal failure requiring dialysis, prolonged Parkinsonism and generalised myopathy. Twenty-two patients with therapeutic intoxication had peak serum lithium concentrations above the therapeutic range. In contrast, of 22 self-poisoned patients with peak serum lithium concentrations above the therapeutic range only 3 developed toxicity. The mean admission plasma urea concentration in patients with therapeutic intoxication was higher than in self-poisoned patients and the mean admission plasma bicarbonate concentration was lower. The mean serum lithium half-life in 8 patients with therapeutic intoxication was considerably longer than in 5 self-poisoned patients. Renal lithium clearance is enhanced by increased sodium excretion and we recommend that lithium toxicity be treated with saline diuresis and frusemide if fluid retention occurs. Haemodialysis is mandatory when renal failure is present, and may be indicated when serum lithium concentrations are very high or rising rapidly.

Adolescent↗
PubMed1986

Inter-subject and ethnic differences in paracetamol metabolism.

The 24 h urinary excretion of paracetamol and its metabolites following a single oral dose of 1.5 g was compared in 111 Caucasians (Scotland), 67 West Africans (Ghana) and 20 East Africans (Kenya). The fractional recovery of the mercapturic acid and cysteine conjugates of paracetamol was 9.3% in the Caucasians compared with only 5.2% and 4.4% in the Ghanaians and Kenyans respectively (P = less than 0.0005). This probably indicates markedly reduced metabolic activation of paracetamol in the Africans. There were no ethnic differences in the sulphate conjugation of paracetamol, but the mean fractional recovery of the glucuronide conjugate in Caucasians (54%) was significantly less than in the Africans (58%). The sulphate conjugation of paracetamol was increased and glucuronide conjugation reduced in Caucasian females compared with males. A similar trend was seen in the Ghanaians but there were no other significant sex differences. The range of intersubject variation in the metabolic activation of paracetamol was sixty fold compared with only a three fold variation in glucuronide and sulphate conjugation. This has important implications for susceptibility to paracetamol hepatotoxicity following overdosage especially in a small subgroup showing extensive metabolic activation. These ethnic differences in paracetamol metabolism may be related to genetic or environmental factors including differences in diet and protein intake.

Acetaminophen↗
PubMed1986

The effect of chloroquine on paracetamol disposition and kinetics.

The effect of chloroquine on paracetamol kinetics and disposition was investigated in six healthy male Ghanaian volunteers. Chloroquine administration shortened the time taken to reach peak plasma paracetamol concentration (tmax) in five of the volunteers. Peak plasma paracetamol concentration (Cmax) was significantly increased by chloroquine administration. The area under the plasma paracetamol concentration-time curve was also significantly increased by chloroquine administration. There was, however, no effect of chloroquine on paracetamol metabolism.

Acetaminophen↗
PubMed1986

Toxicological studies in a Distalgesic addict.

The disposition and kinetics of paracetamol, dextropropoxyphene and their metabolites were investigated in an addict who claimed to be taking 80-100 Distalgesic tablets daily regularly. Plasma concentrations of paracetamol, dextropropoxyphene and their principal metabolites were measured after an oral dose of 15 Distalgesic tablets. The absorption of paracetamol and dextropropoxyphene was rapid with peak plasma concentrations at 15 and 30 min respectively. The elimination half-life for paracetamol was 2.3 h. Nordextropropoxyphene remained at steady state with very high plasma concentrations (5 mg/l). The urinary excretion of paracetamol and metabolites was not abnormal. The total recovery of paracetamol was only 31% of the dose. Apart from raised plasma gamma-glutamyltransferase activity there was no biochemical evidence for paracetamol-induced hepatocellular damage despite ingestion of 97.5 g of paracetamol over the 11 days of the withdrawal period.

Acetaminophen↗
PubMed1986

Effects of non-narcotic analgesics on the liver.

Serious hepatotoxicity is uncommon with the proper therapeutic use of non-narcotic analgesics but experience with new non-steroidal anti-inflammatory drugs (NSAIDs) is limited. Drugs such as ibufenac, fenclofenac and benoxaprofen were withdrawn from the market because of hepatotoxicity, and liver damage has been reported on occasion with virtually all non-narcotic analgesics. However, a clear pattern of toxicity with characteristic clinical, biochemical and histopathological abnormalities has emerged with relatively few. With the exception of acute hepatic necrosis following overdosage of paracetamol, little is known of the mechanisms of liver injury induced by non-narcotic analgesics. Involvement of the liver in a generalised drug reaction does not imply specific hepatotoxicity. About 50% of patients given aspirin regularly in anti-inflammatory doses develop mild, dose-dependent reversible liver damage as shown by elevation of the plasma aminotransferase activity. Liver damage is more severe in a small minority and it may rarely be complicated by disseminated intravascular coagulation and encephalopathy with a fatal outcome. There have also been isolated reports of chronic active hepatitis associated with the use of salicylates. Salicylate hepatitis has been reported most often in young females with connective tissue diseases. Many patients with Reye's syndrome have been given aspirin during the prodromal phase, and this serious condition closely resembles subacute salicylate intoxication in children. Salicylate probably has a causal or contributory role in Reye's syndrome, but many refuse to accept this and the issue is the subject of heated debate. Paracetamol in overdosage causes acute hepatic necrosis, and liver damage has been attributed to its therapeutic use. However, most reports have involved chronic alcoholics who took excessive doses and in these patients the clinical, biochemical and pathological findings were typical of paracetamol overdosage. Many authors have failed to make the distinction between therapeutic use and a therapeutic dose. In other cases liver damage could have been caused by exposure to other agents, viral infection or naturally occurring liver disease. If these cases are excluded, there are very few reports of liver damage associated with the proper therapeutic use of paracetamol. In some cases, the picture resembled chronic active hepatitis but no causal relationship has been established between this condition and paracetamol use. Paracetamol does not cause deterioration in liver function in patients with chronic liver disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Liver damage with non-narcotic analgesics.

Non-narcotic analgesics can produce a variety of hepatic lesions but clinically significant liver damage is uncommon with normal therapeutic use. The pattern of hepatotoxicity caused by the salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen) and the pyrazolones differs but many of these drugs can cause generalised reactions which involve the liver. Depending on the drugs in question, the risks of liver injury may be conditioned by factors such as age, sex, dose and duration of treatment. Hepatotoxicity associated with the use of salicylates and most NSAIDs has been reported most often in females with collagen diseases but this may simply reflect the greater use of these drugs in such patients. Paracetamol-induced liver damage occurs almost exclusively as a result of overdosage. Except for the microvesicular fatty changes in hepatocytes in patients with Reye's syndrome attributed to salicylate, the acute centrilobular necrosis caused by paracetamol in overdosage and the marked cholestasis produced by benoxaprofen, the pathological changes in hepatic reactions to non-narcotic analgesics are rather variable and nonspecific. About 50% of patients given salicylate in full anti-inflammatory dosage develop minor abnormalities of liver function. There is usually a mild to moderate increase in plasma aminotransferase activity with patchy necrosis and degeneration of hepatocytes. These changes are related to plasma salicylate concentration and are usually rapidly reversible. In a small minority of patients, particularly the young, liver damage is more severe and may be associated with liver failure, acidosis, hypoglycaemia and encephalopathy. This picture closely resembles Reye's syndrome. In overdosage, paracetamol can cause acute hepatic necrosis. Without specific treatment, some 8% of adults suffer severe liver damage with plasma aminotransferase activity greater than 1000 U/L and about 1% die with hepatic failure and encephalopathy. The administration of sulfhydryl compounds such as N-acetylcysteine within 8 to 10 hours effectively prevents liver damage and death. Liver damage has been attributed to the therapeutic use of paracetamol. However, in most reports the dose was excessive and many patients were chronic alcoholics (who seem to be at increased risk). In these cases the features were typical of acute overdosage. A consistent and characteristic pattern of hepatotoxicity is evident with relatively few non-steroidal anti-inflammatory and pyrazolone analgesics. A rank order of relative risk cannot be established and the incidence in relation to use is not known.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗
PubMed1986

Treatment of phenobarbitone poisoning with repeated oral administration of activated charcoal.

Six patients with moderate to severe phenobarbitone intoxication were treated with repeated oral doses (50 g) of activated charcoal following an initial dose of 50 to 100 g. All recovered more rapidly than would otherwise be expected with supportive care alone. The mean maximum rate of fall in plasma phenobarbitone concentrations corresponded to a half-life of only 6.2 +/- 2.5 h (normally three to five days); 62 to 93 per cent of the absorbed dose was eliminated within 24 h and the mean total body clearance of the drug during and for up to 12 h after administration of charcoal was 84 +/- 34 ml/min. Treatment with repeated oral doses of activated charcoal is simple and safe. It seems to be as effective as forced alkaline diuresis, haemodialysis and haemoperfusion for the removal of phenobarbitone following overdosage.

Administration, Oral↗