Cloral hydrate

Both alcohol and cloral hydrate are CNS depressants, and their effects may be at least additive, or possibly even synergistic. Some patients may experience a disulfiram-like flushing reaction if they drink alcohol after taking cloral hydrate for several days. 

Studies in 5 healthy subjects given cloral hydrate 15 mg/kg and alcohol... 

The disulfiram-like reaction has been described in other reports. Note that the earliest report was published more than a century ago in 1872 and described two patients taking cloral hydrate who experienced this reaction after drinking half a bottle of beer. ... 

Alcohol, cloral and trichloroethanol (to which cloral hydrate is metabolised) are all CNS depressants. During concurrent use, the metabolic pathways used for their elimination are mutually inhibited blood-alcohol levels rise because the trichloroethanol competitively depresses the oxidation of alcohol to acetaldehyde, while trichloroethanol levels also rise because its production from cloral hydrate is increased and its further conversion and clearance as the glucuronide is inhibited. As a result the rises in the blood levels of alcohol and trichloroethanol are exaggerated, and their effects are accordingly greater.In one subject, blood levels of acetaldehyde during the use of cloral hydrate with alcohol were only 50% of those after alcohol alone, so that the flushing reaction, despite its resemblance to the disulfiram reaction, may possibly have a partially different basis. ... 

It seems likely that cloral betaine, triclofos and other compounds closely related to cloral hydrate will interact with alcohol in a similar maimer, but this requires confirmation. 

The anticoagulant effects of warfarin are increased in the first few days of cloral hydrate use, but this is normally of little or no clinical importance. Cloral betaine and triclofos may be expected to behave similar. ... 

In a retrospective study in patients just starting warfarin, the same loading doses of warfarin were given to 32 patients taking cloral hydrate daily and 67 patient who did not receive cloral hydrate. The warfarin requirements of the cloral group during the first 4 days fell by about one-third, but rose again to control requirements by the fifth day. ... 

In a study in 8 subjects, the concurrent use of warfarin (loading dose 25 mg then 5 mg daily for 5 days) and cloral hydrate 1 g each night resulted in potentiation of the effect of warfarin, when compared with placebo (increase in prothrombin time of about 3 to 4 seconds). However, in a longer term study, the addition of cloral hydrate 500 mg at night for 4 weeks to subjects stabilised on warfarin did not alter the average prothrombin time before, during, and after the cloral treatment (18.9, 19.3, and 19.2 seconds, respectively). ... 

Similar results have been described in other studies in patients taking warfarin and cloral hydrate or triclofos. Qoral betaine appears to behave similarly. An isolated and by no means fully explained case of fatal hypoprothrombinaemia occurred in a patient taking dicoumarol who was given cloral hydrate for 10 days, later replaced by secobarbital." Another patient taking dicoumarol had a reduction in prothrombin times when given cloral hydrate."... 

Cloral hydrate is mainly metabolised to trichloroacetic acid, which then successfully competes with warfarin for its binding sites on plasma proteins. As a result, free and active molecules of warfarin are displaced into the plasma water and the effects of the warfarin are increased. But this is... 

The interaction between warfarin and cloral hydrate is well documented and well understood, but normally of little or no clinical importance. There is very good evidence that concurrent use need not be avoided. " However, it may be prudent to keep an eye on the anticoagulant response during the first 4 to 5 days, just to make sure it does not become excessive. It is not certain whether other anticoagulants behave in the same way because the evidence is sparse, indirect and inconclusive, but what is known suggests that the coumarins probably do. Triclofos and cloral betaine appear to behave like cloral hydrate. Dichloralphenazone on the other hand interacts quite diflerently (see Coumarins+Dichloralphenazone , p.399). 

The phenazone , (p.434) component of dichloralphenazone is a potent liver enzyme inducer, which increases the metabolism and clearance of the warfarin, thereby reducing its effects. The effects of the cloral hydrate , (p.396) component appear to be minimal. 

There is in vitro evidence that the serum binding of warfarin is decreased by sodium valproate so that free warfarin levels rise, by 32% according to one study. The increase in free warfarin levels is transient until a new equilibrium is reached, but theoretically could result in a transient increase in INR, as is seen with cloral hydrate , (p.396). 

Miscellaneous Buspirone, Clomethiazole, Cloral betaine, Cloral hydrate, Eszopiclone, Glutethimide, Hydroxyzine, Meprobamate, Promethazine, Triclofos, Zalepbn, Zolpidem, Zopiclone... 

There is some evidence to suggest that the metabolism of some benzodiazepines (such as alprazolam, bromazepam, diazepam, and also possibly midazolam, nitrazepam and triazolam) may be reduced by some SSRIs (such as fluoxetine and fluvoxamine). On the whole, no clinically significant interaction appears to occur between other SSRIs and the benzodiazepines or related dri s such as cloral hydrate or zaleplon. There is some evidence to support the su estion that sedation is likely to be increased by the concurrent use of SSRIs and benzodiazepines. Rare cases of hallucinations have been seen with zolpidem and some SSRb. Symptoms of the serotonin syndrome have been reported in two patients taking paroxetine and a benzodiazepine. 

In contrast, isolated cases of visual hallucinations lasting up to 7 hours have been reported in patients taking zolpidem who were also taking fluoxetine. Marked drowsiness occurred for a whole day in a patient taking fluoxetine 20 mg daily after being given cloral hydrate 500 mg the night before. She later tolerated cloral hydrate 1 g in the absence of fluoxetine without adverse effects. ... 

Fluvoxamine has been found not to interact adversely with cloral hydrate.Fluvoxamine (50 mg on day one, 100 mg on day 2, then 150 mg daily thereafter) for 16 days decreased the clearance of a single 10-mg dose of diazepam given on day 4 in 8 healthy subjects by about 65%. The half-life was increased from 51 to 118 hours, and the AUC was increased threefold. " ... 

Intravenous injection of furosemide after treatment with cloral hydrate occasionally causes sweating, hot flushes, a variable blood pressure and tachycardia. 

Six patients in a coronary care unit given an intravenous bolus of 40 to 120 mg of furosemide and who had received cloral hydrate during the previous 24 hours developed sweating, hot flushes, variable blood pressure, and tachycardia. The reaction was immediate and lasted for about 15 minutes. No special treatment was given. Furosemide had caused no problems when given before the cloral hydrate was started. ... 

A retrospective study of hospital records revealed that, out of 43 patients who had received both cloral hydrate and furosemide, one patient developed this reaction and 2 others may have done so. The interaction has also been described in an 8-year-old boy. ... 

Not understood. One suggestion is that furosemide displaces trichloroacetic acid (the metabolite of cloral hydrate) from its protein binding sites, which in its turn displaces levothyroxine or alters the serum pH so that the levels of free levothyroxine rise leading to a hypermetabolic state. ... 

An established interaction, but information is limited to three reports. The incidence is uncertain but probably low. Concurrent use ne not be avoided, but it would be prudent to give intravenous furosemide cautiously if cloral hydrate has been given recently. It seems possible that derivatives of cloral hydrate that break down in the body to release cloral hydrate (e g. dichloralphenazone, cloral betaine) might interact similarly. There is no evidence that furosemide given orally or cloral hydrate given to patients already taking furosemide causes this reaction. ... 

A case of fatal hyperpyrexia and another case of serious hypertension have been linked to interactions between cloral hydrate and phenelzine, but in both cases there are other plausible explanations for the reactions seen. 

There is no clear evidence that either of these adverse reactions was due to an interaction between phenelzine and cloral hydrate, and there do not seem to be any other reports to suggest that an interaction between these drugs is likely. 

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