Calcium Carbimide Research Articles

The calcium carbimide‐ethanol interaction: Effects of ethanol dose

In a double-blind, placebo-controlled study involving five male alcoholic volunteers, oral administration of 0.7 mg/kg of calcium carbimide (CC) 12 hr before ingestion of ethanol (0.125, 0.25, and 0.5 gm/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia, and decreased diastolic blood pressure. The order of intensity of the interaction with regard to ethanol dose was 0.5 greater than 0.25 greater than 0.125 k gm/kg. The subjects were aware of a CC-ethanol interaction only for 0.25 and 0.5 gm/kg of ethanol, for which heart rate was elevated above 100 bpm. With the criterion of heart rate above 100 as indicative of the CC-ethanol interaction, the onset was 0.25 and 0.38 hr for the 0.5 and 0.25 gm/kg ethanol doses and the duration of the interaction was 1.0 and 0.38 hr, respectively. There were positive linear correlations between blood acetaldehyde level and both heart rate and pulse pressure. There was appreciable individual variability in the intensity and duration of the interaction. Pretreatment with CC reduced the rate of ethanol metabolism at the 0.5 gm/kg ethanol dose.

Drug-induced peripheral neuropathies.

Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely.

The presence of an aldehyde dehydrogenase inhibitor in animal diets and its effects on the experimental results in alcohol studies.

1. The effects of chronic ethanol administration on the metabolism of ethanol and acetaldehyde were studied in rats fed on a commercial diet containing an aldehyde dehydrogenase inhibitor, calcium cyanamide (calcium carbimide), as a contaminant in the calcinated bone-meal fraction of the diet. 2. Rats given an ethanol solution (150 ml/l) for 3 months and fed on a diet containing calcinated bone meal showed two times higher activity of the low-Km acetaldehyde dehydrogenase in the liver, 26% higher rate of ethanol elimination, and two to three times lower acetaldehyde levels in blood during ethanol elimination compared with control rats pair-fed on the same diet. 3. The results obtained from the ethanol-treated rats were similar to those obtained in experiments on control rats fed on diets not containing calcinated bone meal. 4. Experiments performed in vitro and in vivo on the inhibition of the acetaldehyde metabolism by cyanamide suggested that the apparent effects of chronic ethanol intake were really caused by calcium cyanamide in the diet.

A study of the calcium carbimide-ethanol interaction in man.

In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4 greater than 8 approximately 12 greater than 24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.

Chemical aversion treatment of alcoholism: Lithium as the aversive agent

Animal work indicating flavour aversion produced by chemical aversion therapy (CAT) with lithium might be effective in the treatment of alcoholism led to this treatment being given to 25 patients. The abstinence rate six months later of 36% was significantly better than the 12% rate for an equivalent group of patients, treated with a disulfuram-like drinking deterrent, calcium carbimide. The rate for the CAT group improves to 47% if 8 patients are excluded who did not develop sickness reactions to lithium. CAT with lithium appears safe given proper medical precautions.

Primary hyperoxaluria with normal alpha-ketoglutarate: glyoxylate carboligase activity. Treatment with isocarboxazid.

A 10-year-old girl with primary hyperoxaluria, calcium oxalate nephrolithiasis, and normal blood urea was studied. Despite high urinary oxalate and glycolate excretion, normal activity of α-ketoglutarate:glyoxylate carboligase was observed in both mitochondria-containing and soluble cytoplasmic fractions of striated muscle tissue. No effect on the urinary excretion of oxalate or glycolate was observed with the administration of pyridoxine, allopurinol, or calcium carbimide. A 40% reduction in urinary oxalate excretion was produced by isocarboxazid therapy. Further studies are necessary to elucidate the role of monoamine oxidase inhibitors in the treatment of primary hyperoxaluria.

Transplantation and Renal Oxalates

To the Editor:— In the report entitled Failure of Renal Transplantation in Primary Oxalosis, ( 209 : 551, 1969), I overlooked that there is a statement which says, We believe that transplants should not be performed in primary oxalosis. I do not think that this particular case proves this point. At autopsy, there was listed moderate stenosis of the right renal vein at the site of the anastomosis. I do not believe that we can conclude that the loss of the kidney was solely due to the deposit of oxalate crystals within the substance of the kidney alone. It is certainly possible that Dr. Solomons' work on calcium carbimide might save transplants in this condition.

Investigation of possible effect o f calcium carbimide on urinary oxalate excretion in primary hyperoxaluria.

Investigation of possible effect o f calcium carbimide on urinary oxalate excretion in primary hyperoxaluria.

Klinische Erfahrungen und biochemische Aspekte bei der Behandlung des Alkoholismus mit Calciumcarbimid (DIPSAN)

The substance calcium carbimide (DIPSAN) which produces alcohol intolerance was tested on 72 alcoholics aged 23—66 years. Unlike the well-known disulfiram (ANTABUS), which obviously inhibits a large number of ferments, calcium carbimide appears to act selectively on acetaldehyde dehydrogenase. The results of an alcohol—dipsan reaction are therefore easier to check, more constant, and lack unpredictable complications. In the foreground is facial flushing, and to a lesser degree of other parts of the skin. Trunk and extremities may be affected in patches. If the contraindications are kept in mind (patients with hypertony, decompensated heart disease, cerebral circulatory disturbance, bronchial asthma, kidney disease, stomach and intestinal ulcers, and pregnancy) massive undesirable side effects and complications are seldom to be feared. Our investigations of blood chemistry show the following differences from disfuliram: 1. The fasting levels of acetaldehyde rose after the administration of disulfiram even without alcohol being consumed. This seems to be connected to the fact that as a rule the administration of disulfiram will produce mild symptoms such as headache and dizziness. The rise is much smaller in the case of calcium carbimide so that without alcohol it is well tolerated even over longer a period, and virtually without discomfort. 2. After the consumption of alcohol the acetaldehyde levels in patients treated with calcium carbimide are much higher than in those on disulfiram. There appears to be a direct relationship between the level of acetaldehyde and the degree of the reaction to alcohol with calcium carbimide. These findings are related to the selective inhibition of acetaldehyde hydrogenase. 3. 1 or 2 hours after the first dose of calcium carbimide a complete alcohol reaction is achieved, which means that preparative treatment as with disulfiram is not necessary. 4. In contrast to patients treated with disülfiram, in whom the cumulative effect can still produce a marked intolerance of alcohol even 7—10 days after completion of treatment, those taking calcium carbimide, even for prolonged periods, show only negligible signs of intolerance 48 hours after the last dose.

Treatment of primary hyperoxaluria with calcium carbimide.

VARIOUS measures have been proposed to reduce the endogenous production of oxalic acid in patients with primary hyperoxaluria; these include the oral administration of sodium benzoate,1 pyridoxine,2 hydroxymethane sulfonic acid3 and allopurinol.4 Recently, Solomons and his colleagues5 have proposed the use of calcium carbimide on the grounds that this compound would inhibit the enzymic oxidation of glycolaldehyde to glycollic acid and hence the production of oxalic acid (Fig. 1). These authors reported that oxalate excretion was reduced to near normal values during the oral administration of citrated calcium carbimide (25 to 37.5 mg daily) to a patient with primary hyperoxaluria. . . .

The effects of calcium carbimide and thyroid powder on thyroid morphology and feed efficiency in rats

Rats treated with 10, 20, 40, or 80 mg/kg/day of calcium carbimide showed a dose-related depression of body weight gain, food consumption, and feed efficiency that was greatest at the 80 mg/kg/day dose level. Histometric quatiification of the thyroid glands of these animals showed a marked hyperplasia of follicular epithelium, loss of colloid, and capillary hyperemia compared with control animals. Administration of 80 mg/kg/day of thyroid powder together with 80 mg/kg/day of calcium carbimide resulted in a marked increase in total food consumption with a concurrent decrease in feed efficiency and produced a colloid “storage phase” in the thyroid gland. The physiologic change characterized by a reversal of the morphologic pattern of the thyroid gland from severe hyperplasia to colloid storage may be interpreted as indicative of a significant decrease in the activity of the thyroid gland.

The influence of disulfiram and calcium carbimide on the serum diphenylhydantoin. Excretion of HPPH in the urine.

TWO DRUGS are used as aids in the treatment of chronic alcoholism in Denmark, namely disulfiram (Antabuse) and calcium carbimide (Dipsan). An increase in the diphenylhydantoin content of the serum 1 was found in patients given this drug in combination with disulfiram. The administration of the usual therapeutic dose of disulfiram (400 mg daily) for nine days was followed by an increase in diphenylhydantoin content in the serum by 100% to 400%. The aim of this study was to determine if the rise in serum diphenylhydantoin caused by disulfiram is the result of inhibition of the conversion of diphenylhydantoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) in the liver. Furthermore, we wished to determine whether the administration of calcium carbimide causes an increase in the diphenylhydantoin content of the serum in patients with epilepsy who require therapy for chronic alcoholism. Material and Methods Six male patients who had been treated with diphenylhydantoin for

Comparative studies on the morphologic effects of calcium carbimide, propylthiouracil, and disulfiram in male rats

The morphologic effects of dietary administration of calcium carbimide were evaluated in comparison with propylthiouracil and disulfiram in male rats. In addition, the regression of some of the drug-induced lesions was studied during and after a 16-week recovery period. Increasing diet concentrations up to 0.2% of calcium carbimide administered for 14 weeks caused general inhibition of growth, general edema, morphologic activation of the thyroid gland accompanied by regressive changes of the acidophilic and thyrotrophic cells in the anterior portion of the pituitary gland, regressive transformation of the adrenal cortex, and dystrophic changes in the testes. A hemolytic anemia which led to a slight siderosis of the spleen, postnecrotic liver fibrosis, and osteoporotic changes in the femur were also found at the end of the experiment but could not be related to hypothyroidism. The antithyroid effect of calcium carbimide was more pronounced than that of propylthiouracil. With the exception of a slight siderosis of the mesenteric lymph nodes, disulfiram produced no toxic effects. Some of the harmful drug effects such as the morphologic activation of the thyroid gland, the dystrophic cellular changes in the pituitary gland, the regressive transformation of the adrenal cortex, the postnecrotic liver fibrosis, and the osteoporosis showed signs of regression during and after a recovery period of 16 weeks.

Comparative Clinical Study of the Effects of Disulfiram and Calcium Carbimide. II. Reaction to AlcohoI

Comparative Clinical Study of the Effects of Disulfiram and Calcium Carbimide. II. Reaction to AlcohoI

Comparative Clinical Study of the Effects of Disulfiram and Calcium Carbimide. I. Side Effects

Comparative Clinical Study of the Effects of Disulfiram and Calcium Carbimide. I. Side Effects

Citrated Calcium Carbimide in the Treatment of Alcoholism

Clinical trials have proved citrated calcium carbimide (CCC) to be a valuable agent in treating chronic alcoholism. Fewer side effects occur with use of this drug than with disulfiram. Reaction to alcohol intake begins within five minutes after administration of CCC. Maximal effect is observed within 30 minutes to an hour.The authors report the results of a study in which CCC was administered to 24 adults, including five normal subjects and 19 alcoholics. Improvement was noted in four subjects, and alcoholism was alleviated in eight.

Citrated calcium carbimide in the treatment of the alcoholic.

Citrated calcium carbimide in the treatment of the alcoholic.

Disulfiram and citrated calcium carbimide in the treatment of alcoholism.

Since disulfiram (tetraethylthiuram disulphide) was first reported to cause intolerance to alcoholic beverages (Haldet al., 1948) it has been used extensively as an adjunct in the treatment of alcoholism. Impressions of most therapists have been favourable (e.g. Martensen-Larsen, 1953; Wallersteinet al., 1957). At Warlingham Park Hospital the drug has been administered over the past five years to more than 250 alcoholics (as part of a fairly comprehensive therapeutic programme—Glatt, 1955) and has been found by a great many patients very helpful after discharge from hospital.

Use of citrated calcium carbimide in alcoholism.

Effective control of alcoholism by chemotherapy dates from 1943, when Asmussen and co-workers¹and Jacobsen and Martensen-Larsen²first described the reaction of patients receiving disulfiram and alcohol. In 1951, Graham³demonstrated that disulfiram interferes with the metabolism of alcohol by inhibiting it at the acetaldehyde stage. Physical symptoms of the alcohol-disulfiram reaction (flushing, headache, tachycardia, and dyspnea) are believed to be due to the accumulation of acetaldehyde, and these symptoms are sufficiently unpleasant to serve as deterrents to further drinking. The value of disulfiram has been generally recognized, but its application has been limited by certain unpleasant side-effects, the most common of which are gastrointestinal disturbance, impaired taste, unpleasant breath and perspiration odors, lassitude, drowsiness, and diminished sexual potency. In 1953, Fergusen⁴reported that citrated calcium carbimide (Temposil) in the presence of ingested alcohol produced an acetaldehyde reaction similar to that of disulfiram and alcohol. Either

Use of citrated calcium carbimide (temposil) in treatment of chronic alcoholism.

A single dose of 50 mg. of citrated calcium carbimide will sensitize an individual to alcohol. After treatment with calcium carbimide, conjunctival injection, flushing of the face, headache, and dyspnea were routinely seen 5 to 10 minutes after sufficient alcohol was taken to initiate a reaction. The alcohol reaction reached a maximum in about 30 minutes and usually lasted from 60 to 90 minutes, after which the patient felt lethargic and drowsy. The most striking and reassuring observation was the infrequency with which acetaldehyde shock developed. In only 6 of 73 male patients were the objective findings such as to cause concern; 4 of these patients became cyanotic, one developed a generalized tremor with chilling and marked apprehension, and the 6th patient was a known asthmatic who became very dyspneic at the height of the reaction.