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At least 109 records · Page 6Linked to original sources
PubMed1989

Chlormethiazole sedation for critically ill patients in renal failure.

Chlormethiazole infusions were used successfully to provide night sedation for 10-19 nights in three patients with renal failure managed by continuous veno-venous haemofiltration with dialysis. Fluid overload has accompanied the use of this drug previously because of its low concentration. The ability to remove large amounts of fluid during haemofiltration dialysis proved to be effective in preventing this. All three patients had impaired liver function and showed evidence of chlormethiazole accumulation after 4-6 days. The combination of progressive reduction in dose and daily withdrawal of infusions prevented a major problem. Acceptance of this technique by the patients was high. Chlormethiazole may be a useful addition to the drugs available to provide sedation in well defined clinical circumstances.

Adult↗
PubMed1979

Influence of chlormethiazole on cerebral blood flow and oxygen consumption in the rat, and its effect on the recovery of cortical energy metabolism after pronounced, incomplete ischaemia.

The influence of an anaesthetic dose of chlormethiazole (Hemineurin) on blood flow (CBF) and oxygen consumption (CMRO2) in the rat brain was investigated. In spontaneously breathing animals a dose of 160 mg . kg-1 of chlormethiazole, infused i.v., induced a state close to surgical anaesthesia. In paralyzed animals, the same dose decreased CBF and CMRO2 to about 60% of control, an effect similar to that observed after an anaesthetic dose of phenobarbitone. Neither a protective nor a detrimental effect of chlormethiazole could be demonstrated when the drug was given during reversible and pronounced, incomplete ischaemia, as evaluated from the postischaemic tissue concentrations of labile phosphates (PCr, ATP, ADP, AMP) and of lactate and pyruvate. It is concluded that protection in this situation (as earlier shown with phenobarbitone) must, at least partly, be related to other mechanisms than a depression of metabolism.

Anesthesia, General↗
PubMed1986

A comparison of chlormethiazole and thioridazine in agitated confusional states of the elderly.

Chlormethiazole and thioridazine were found to be equally effective in the management of the agitational component of agitated confusional states in the elderly. Confusion and nocturnal awakening were found to be controlled more effectively with chlormethiazole than with thioridazine. Chlormethiazole treatment also resulted in significant reductions in physical disability as assessed by the Clifton Behaviour Rating Scale. A greater incidence of adverse effects was associated with thioridazine treatment.

Aged↗
PubMed1986

Chlormethiazole in intensive care.

Patients in the intensive care unit frequently require sedation. The advantages of using an intravenous infusion of chlormethiazole to produce sedation include the rapidity of sedation and recovery, and the lack of cardiovascular effects. Chlormethiazole is contraindicated in patients with hepatic failure or those in whom central nervous system functioning has to be assessed. Provided care is taken, chlormethiazole is a very valuable agent in treating patients in an intensive care unit.

Adult↗
PubMedDate not supplied

Intravenous chlormethiazole in the management of primary trigeminal neuralgia resistant to conventional therapy.

The therapeutic efficacy of 0.8% chlormethiazole, administered as 3-10 intravenous infusions each lasting 5-6 h on alternate days, was assessed in an uncontrolled study of 16 patients, aged 44-82 years, with primary trigeminal neuralgia. Prior to entry into the study, patients showed a high frequency of neuralgic paroxysms (20-70 attacks/day) which were refractory to high dosages (1600-2000 mg/day) of carbamazepine. After treatment with chlormethiazole neuralgic paroxysms no longer occurred in five patients, were considerably reduced in intensity and frequency (less than or equal to 5 attacks/day) in six patients, moderately improved in two patients, slightly improved in one patient and showed no change in two patients. The relatively small number of cases and short post-treatment follow-up period limit the conclusions which can be drawn. These results indicate, however, that infusion with chlormethiazole is effective in the treatment of primary trigeminal neuralgia in patients for whom conventional therapy has been unsuccessful.

Aged↗
PubMed1986

Charcoal-column haemoperfusion does not significantly enhance chlormethiazole removal.

A 26-year-old man had convulsions after taking an overdose of slow-release aminophylline tablets. The convulsions were treated with an infusion of chlormethiazole and theophylline was removed by charcoal-column haemoperfusion. It has been suggested that haemoperfusion might be useful for removing chlormethiazole and this was investigated. There was no evidence that charcoal-column haemoperfusion could remove clinically significant amounts of chlormethiazole.

Adult↗
PubMed1979

The effect of chlormethiazole on serum gonadotrophins and testosterone in chronic alcoholics.

Serum gonadotrophins (LH and FSH) and testosterone concentrations were estimated by radioimmunoassay in 7 male chronic alcoholics on admission and following treatment with chlormethiazole for 6 days. Individual and mean values of serum LH and FSH were within normal limits both before and after treatment, but serum testosterone concentrations were found to be slightly higher than normal on both occasions. Chlormethiazole does not seem to have any effect on serum gonadotrophins or testosterone. It is further suggested that chlormethiazole does not interfere with the hypothalamic releasing factors for pituitary gonadotrophins and that it has no direct effect on testicular endocrine functions.

Adult↗
PubMed1976

Physiological dependence on, and symptoms of withdrawal from, chlormethiazole.

The uses of chlormethiazole (Heminevrin) are briefly mentioned. Differing views of its potential for producing dependence are discussed. The consensus opinion is taken to be that a risk of psychological dependence does exist, but only one case has appeared in the medical literature to date of physiological dependence on chlormethiazole, with withdrawal symptoms. This case is re-examined. A second case is described in which the features of increasing dosage and withdrawal were followed by confusion, disorientation, delusions, hallucinations and muscular spasm and coarse jerking. This is taken as confirmation of the potential of chlormethiazole to produce physiological dependence. Some personal opinions of the author regarding indications for use and incidence of abuse are briefly mentioned.

Adult↗
PubMed1979

Chlormethiazole abuse.

This report describes 17 cases of chlormethiazole abuse or dependence. These include one case with symptoms and signs of withdrawal and two other similar cases where undoubted dependence was combined with excessive alcohol intake. Seven other patients with alcoholism who indulged in drug-seeking behaviour involving chlormethiazole are also reported, together with a further seven abusers of various other drug who were also discovered to be taking chlormethiazole.

Adult↗
PubMed1975

Metabolism and urinary excretion of chlormethiazole in humans.

1. Chlormethiazole and five of its metabolites excreted in urine in man have been investigated by g.l.c.-mass spectrometry. 2. Four metabolites have been identified by comparison with authentic compounds as 5-acetyl-4-methylthiazole, 5-(1-hydroxyethyl)-4-methylthiazole, 5-(2-hydroxyethyl)-4-methylthiazole and 4-methyl-5-thiazoleacetic acid; 4-methyl-5-thiazoleacetaldehyde is proposed for the other metabolite. 3. The amounts of chlormethiazole and its identified metabolites excreted in urine have been quantitatively determined after a single oral dose in three healthy adults. Approximately 16% of the dose was excreted as chlormethiazole, 5-acetyl-4-methylthiazole, 5-(1-hydroxyethyx)-4-methylthiazole and 4-methyl-5-thiazoleacetic acid.

Adult↗
PubMed1988

[Treatment of refractory status convulsivus with chlormethiazole].

A 5 years old girl with status epilepticus refractory to treatment with Diphenylhydantoin at a dose of 30 mg/kg/day and Thiopental in continuous IV perfusion at a dose of 4 mg/kg/h is presented. Control of status was achieved by continuous IV perfusion of Chlormethiazole at a dose of 10 mg/kg/h which also caused respiratory depression. Seizure activity reappeared after IV perfusion of Chlormethiazole was retired, and could be controlled only with Sodium Valproate. Mechanisms of action of Chlormethiazole and its effectiveness in treatment of refractory status epilepticus are revised.

Child, Preschool↗
PubMed1978

Kinetics of chlormethiazole in patients with alcohol withdrawal manifestations.

Chlormethiazole administered orally to patients in mild degrees of alcohol withdrawal was generally rapidly absorbed, showed a rapid distributive phase, and had an elimination phase 1 1/2 of 2.6 to 4.7 hr. The plasma concentrations of drug attained following higher oral doses were greater than is usually the case with augmentation of dose. Intravenously infused chlormethiazole in similar patients produced relatively high plasma concentrations of the drug, with distributive and eliminative 1 1/2 similar to those of oral doses. These pharmacokinetic patterns in alcoholic patients more closely resemble those previously reported for normal young subjects than they do for normal aged subjects.

Administration, Oral↗
PubMed1982

The effect of chlormethiazole on plasma adrenocorticotrophic hormone concentrations in chronic alcoholics.

Plasma adrenocorticotrophic hormone (A.C.T.H.) levels were estimated by radioimmunoassay in 20 male chronic alcoholics (mean age +/- SD - 40.55 +/- 7.83) both before and during treatment with chlormethiazole. There was no statistically significant difference between the pre-treatment (mean +/- SD =25.25 +/- 14.87 ng/1) and post-treatment levels (mean +/- SD = 26.45 + 15.32) of plasma A.C.T.H. (paired "t" = 1.83; N.S; log transform "t" = 2.79; N.S; p less than 0.05). So, chlormethiazole has not been found to influence plasma A.C.T.H. levels adversely but because of its sedative effect, it may eliminate the ethanol-induced stress thereby helping indirectly in reducing the elevated levels. Plasma A.C.T.H. levels seem to be raised in some patients due to chronic ethanol ingestion and total abstinence for more than a week might be needed for the raised levels to return towards normal diurnal pattern.

Adrenocorticotropic Hormone↗
PubMed1994

Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA ('Ecstasy') to rats.

An investigation has been made into the effect of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') administration on the concentration of 5-hydroxytryptamine (5-HT), uptake of [3H]5-HT and [3H]paroxetine binding in rat cerebral cortex tissue. Four days after 2 injections of MDMA (20 mg/kg i.p., 6 hr apart) the concentrations of 5-HT and its metabolite 5-HIAA were reduced by 60%. The binding of [3H]paroxetine to the presynaptic 5-HT transporter was decreased and high affinity uptake of [3H]5-HT was reduced by a similar amount, indicating neurodegeneration of 5-HT terminals. Pretreatment with chlormethiazole (100 mg/kg i.p.), 10 min before each MDMA injection prevented the decrease in both [3H]parotextine binding and uptake of [3H]5-HT. The loss in 5-HT and 5-HIAA content was also attenuated. Pretreatment with dizocilpine (1 mg/kg i.p.) or haloperidol (2 mg/kg i.p.) also prevented the MDMA-induced loss of [3H]paroxetine binding and attenuated the loss of 5-HT and 5-HIAA content. All three compounds also decreased the degree of hyperthermia that follows MDMA administration, although previous studies suggest that the long term neurodegeneration is not associated with the acute hyperthermic response. These data support the findings of others that MDMA injection produces degeneration of 5-HT nerve terminals in the cortex, confirm that chlormethiazole, dizocilpine and haloperidol attenuate MDMA-induced neurotoxic loss of 5-HT and demonstrate for the first time that these compounds prevent the neurodegeneration of 5-HT nerve terminals that follows MDMA administration.

Animals↗
PubMed1988

Interactions of carbamazepine, chlormethiazole and pentobarbitone with adenosine on hippocampal slices.

1. The effects of the anticonvulsants carbamazepine, chlormethiazole and pentobarbitone and their interactions with adenosine have been studied in rat hippocampal slices. 2. Neither chlormethiazole nor pentobarbitone changed the evoked population spike in CA1 stratum pyramidale, while carbamazepine produced a gradual decline of this potential at concentrations of 100 microM or greater. 3. This effect was not prevented by 8-phenyltheophylline. 4. Only carbamazepine (greater than 20 microM) produced any change of adenosine responses: a slowly developing reduction of the inhibitory action. 5. None of the anticonvulsants altered responses to the amino acid excitant N-methyl-aspartate, or kynurenic acid.

2-Chloroadenosine↗