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Biomedical subjects

J L Crammer

Publications and source records attributed to J L Crammer.

At least 37 records · Page 2Linked to original sources
PubMed1985

Phenolic metabolites of thioridazine in man.

After oral administration of thioridazine or mesoridazine to man, faecal extracts contained mainly unconjugated 7-hydroxy-thioridazine and its demethylated analogue, together with some 3-hydroxy-thioridazine, and 7-hydroxy derivatives of sulphoridazine and desmethyl sulphoridazine. In contrast, urine contained free 7-hydroxy-mesoridazine, and no free 7-hydroxy-thioridazine was detectable. Conjugates of all these phenols were also found. After oral sulphoridazine administration (thioridazine side-chain sulphone), urine contained mainly 7-hydroxy-sulphoridazine and faeces both 7-hydroxy-sulphoridazine and its desmethyl analogue. Sulphoridazine metabolism is therefore much simpler than that of thioridazine. This different elimination pattern in faeces and urine may be due to reduction of sulphoxides but not sulphones by intestinal bacteria.

Administration, Oral↗
PubMed1980

A pilot of plasma thioridazine and metabolites in chronically treated patients.

Plasma concentrations of thioridazine, mesoridazine, sulphoridazine and thioridazine ring sulphoxide have been measured individually by specific gas-liquid chromatographic (GLC) methods, and collectively by a radio-receptor assay, in 16 elderly in-patients during chronic treatment. The sulphoridazine level was above 0.135 microgram/ml in 5 out of 6 symptomatically well-controlled patients, and below this level in 9 out of 10 who were poorly controlled. No such division was so clear for the other substances measured. A new assay for the total dopamine receptor-blocking activity of the plasma correlated highly at lower levels with the sum of drug plus metabolites obtained by GLC, but exceeded the sum at higher values. Both sulphoridazine and neuroleptic levels need further study.

Aged↗
PubMed1979

Lithium concentration and clinical responses.

The clinical use of measurements of drug concentrations in blood is empirical and largely confined to compliance and toxicity monitoring. As currently used in once or thrice a day dosage, lithium treatment is pulsatile, the blood concentration varying threefold over 24 hours; routine measurements reveal nothing of this and therefore do not aid therapeutic use. In a pilot study it is shown that the plasma lithium concentration can be raised from 0 to 2 mmol/l in a few hours, inducing changes in both kidney function and neuropsychological tests after only short delay. This suggests that mania might be quickly controlled with rapid dosage and opens up a new way of analysing the mechanisms of lithium action, or of using it to reveal changes in cerebral functioning.

Diuresis↗
PubMed1978

Psychosis in young doctors.

Three young men who had serious psychotic illnesses as final-year medical students, with damaging recurrences later in two, have subsequently succeeded as clinical practitioners. One has so far completed five healthy years, the others two years each, since treatment with phenothiazines and support.

Humans↗
PubMed1977

Measurement of thioridazine in blood and urine.

1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non-specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine-plus-sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0-7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half-life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding.

Chromatography, Gas↗
PubMed1977

Hormone responses to methylamphetamine in depression: a new approach to the noradrenaline depletion hypothesis.

The corticosteroid response to methylamphetamine was lower in ten patients when they were depressed than when they were recovered (P less than .026). The growth hormone responses to the same injection in the depressed and recovered states were not significantly different. This pattern of responses is seen in normal subjects after blockade of alpha adrenergic receptors. These findings may indicate a functional deficiency of noradrenaline at alpha adrenergic receptors in these patients during the time they are depressed.

Adrenal Cortex Hormones↗
PubMed1976

Change in diurnal temperature rhythm in manic-depressive illness.

The temperatures of six manic-depressive patients were taken every three hours consecutively for many weeks, covering at least one depressive and one manic episode in each patient. While the daily temperature curve was essentially normal in manic phases, with pronounced 24-hour rhythm, during depression the daytime temperatures appeared disorganised, often falling during the morning instead of rising, and with suggestions of a 12-hour rhythm. It may be useful to look on manic-depressive illness as resulting from a desynchronisation of circadian rhythms and to compare the pharmacologies of temperature regulation and mood regulation in psychosis.

Adult↗
PubMed1974

Blood levels and management of lithium treatment.

The limited value of plasma measurements in the management of treatment with lithium is discussed in the light of the mechanisms of its therapeutic actions and toxic effects.The plasma level of lithium usually rises twofold or threefold in the three to five hours after ingestion of each dose of delayed-release tablets and then gradually falls. The precise shape and height of the lithium curve depend on gastric emptying, which can be slowed with propantheline or speeded with metoclopramide. Depressed or demented patients may be irregular in taking their tablets and variable in food intake. Both the time of the blood test and this behaviour must be considered before changing the prescribed dose of lithium salt because of a laboratory result. A lithium tolerance curve may be a safer guide to treatment than single measures.Mild intermittent thirst is a common early side effect, and severe persistent thirst with polyuria is an uncommon later effect of daily intakes of at least 1,500 mg lithium carbonate. This diabetes insipidus is reversible, non-progressive, unrelated to plasma level, and distinct in attack from lithium-induced hypothyroidism, which may occur at low dosage but is also usually of late onset and reversible or treatable with thyroxine while lithium is continued. Obesity is another occasional effect of large doses. These side effects and the antimanic and prophylactic effects may have different mechanisms.

Administration, Oral↗
PubMed1972

Benzhexol and side effects with long-acting fluphenazine therapy.

Sixteen patients who had for some months been on fluphenazine enanthate injections (1-3 ml) every two or three weeks, with daily oral benzhexol (6-40 mg), were divided into two groups comparable in age, diagnostic category, and drug dose.Placebo was substituted under blind controlled conditions for benzhexol in one group, and both groups were regularly assessed by Simpson rating scale for extra-pyramidal signs, and by a 30-question symptom check list. Both assessments were found reliable.Four out of eight patients had severe reactions when off benzhexol, but symptoms such as tremor and daytime sleepiness were unaltered in all patients. The other four did not suffer adversely from withdrawal of benzhexol.Acute withdrawal is therefore unjustified, but occasional revision of dosage of anti-Parkinsonian drugs is advisable. There is no evidence that tolerance develops to any effect of a phenothiazine, but long-continued benzhexol might induce a denervation supersensitivity. It is also possible that Parkinsonian signs are dependent on affective state.

Administration, Oral↗