The History Of Disulfiram (Antabuse) In The Treatment Of Alcoholism
For 40 years the Disulfiram was the drug causing alcoholism which was most often used by the American doctors for treatment of alcohol addiction. Lower about indications and efficiency of this drug.
The Disulfiram will cause unpleasant reaction with ethanol, usually in a dose from 250 to 500 mg/day though at some patients at this level reaction with disgust can be absent. The warm, hepatic and neurologic toxicity can also arise in this range of doses.
If it is necessary to use a disulfiram, the patient has to understand accurately risk of alcohol intake during administration of drug, and the doctor and the patient have to agree about need of constant clinical observation and monitoring of efficiency and side effects. The doctor also has to recognize that the disulfiram is only additional therapy and that continued support, observation and other therapeutic measures is required.
- Antabuse, is possibly effective in decrease in frequency of alcohol intake at the pliable patient during the short period (for example, 6 months). Certain subgroups of patients, for example, those who are more senior those who are more socially steady, and those who are motivated can test positive effect during longer periods
- Antabuse can be the most effective in decrease in short-term alcohol intake when the patient is under observation. Purpose of a disulfiram without the accompanying training, consultation and the accompanying therapy of alcoholism is not favorable
- Disulfiram has no proven effect on the remote consequences of alcoholism. and the accompanying therapy of alcoholism is not favorable
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. | Am J Med 1991 Oct;91(4):446.
Sometimes it happens that random observations lead to great discoveries. These discoveries will wash the non-trivial thinking of the researchers. For example, A. Becquerel "accidentally" discovered radioactivity, and A. Fleming - penicillin. A similar story happened with the Danish doctor and researcher Oluf Martensen Larsen.
In the first synthesis of the compound Disulfiram known since 1881, in the work of the German chemist M. Grodzki. Then, a minor discovery brought it back into the spotlight, finding its use in the rubber industry to speed up vulcanization. It was here that E. Williams drew attention to workers engaged in the processing of substances after drinking alcohol. For more than 200 years, Disulfiram and related chemicals have been used in the rubber industry as catalytic accelerators of vulcanization (stabilization) of rubber by adding sulfur. 117 In the early 1900s, workers exposed to Disulfiram developed adverse reactions to exposure to ethanol. American doctor Williams suggested that disulfiram may be a useful supplement in the treatment of alcoholism.
Sciences - Williams EE. Effects of alcohol on workers with carbon disulfide
The creation of the drug Antabuse
However, the leading character within the story with the Antabuse was Dr. Eric Jacobsen (1903-1985), UN agency was prof of medicine at the University of national capital. within the Forties, he and Dr. Jens Hald began acting on the metabolism of copper enteric parasites, that is that the main metal within the metabolism pigment of helminths. They found that Antabuse will kind chelate with copper, resulting in the death of organisms. throughout these years, Dr. Jacobsen took up the position of head of the organic chemistry laboratory of the Danish pharma healthful Co. Inc., that straight off took an interest in these results. At that point, thanks to the harm caused by the Second war, itch and enteric worms were major public health issues, and so the Antabuse was quickly raised at the height of recognition.
Then there have been positive results of his action on rabbits, and Dr. Jacobsen, at home with attempting new medication on himself, determined to subject himself to Antabuse. terribly quickly he realised that "the Antabuse tablets very modified the result of alcohol within the most undesirable direction." once similar results were obtained from his partner, Dr. Hold, they thought of victimization this substance within the treatment of patients with alcohol-related disorder. However, the thought aroused heat interest as a result of white plague wasn't thought of an enormous enough drawback.
Later, at the urging of Dr. Oluf Martensen Larsen, associate degree professional within the treatment of alcohol patients, UN agency pointed to the large potential of the drug as a deterrent to alcohol, interest within the drug was once more supported. Another random commixture of the Antabuse sample with copper resulted in an exceedingly higher molecule with a bigger surface and simply absorbed in organisms. later on, this molecule was proprietary underneath the Danish name Antabuse in 1952, however before long became referred to as Antabuse - this name not solely witnessed its quality, however conjointly witnessed its purpose.
Interesting fact about acetaldehyde
This story had another breakthrough, that happened quite inadvertently, once one in all their colleagues suddenly entered their laboratory with the "smell of acetaldehyde", which Dr. Jacobsen unnoticed, for ages engaged within the area, puzzling over the mechanism Actions. , Later, Hald and Jacobsen were ready to demonstrate elevated levels of ethanal within the blood, further as within the exhaled air. By now, due to the previous work of Dr. Eric Widmark, it had been documented that plant product is metabolized within the liver by consecutive changing ethanal so into carboxylic acid exploitation the catalyst alcohol and organic compound dehydrogenase consequently. They then known that the drug works by inhibiting organic compound dehydrogenase, that ends up in the buildup of ethanal.
This was followed by a series of articles, ab initio in Scandinavian magazines, followed by publications within the European and yank communities. alternative researchers additionally began exploitation the drug with promising results. Dr. Martinsen Larsen reportable the utilization of medicine in eighty three patients, of that regarding five hundredth were ready to "significantly win." Researchers like Dr. Eric Glud additionally pointed to the necessity to optimize the treatment plan to mirror variations in alcohol consumption patterns within the yank and Scandinavian communities.
Later, studies on the molecule began to diversify within the vary from the interaction of disulfiram-ethanol to the pathophysiological effects of ethanal made. Studies of medicine not solely excited studies of alcohol metabolism, however additionally joined the chemical and medicine aspects resulting in the invention of another substances which will cause a reaction with alcohol, like tetramethyl taurus monosulfide, that were terribly almost like medicine.
That's however the formula of this substance is represented within the language of chemical science - (carbonothioyl nitrile) tetraethyl, or "Tetraethyl thiuram disulfide ", formula: C10H20N2S4.
Action of the disulfiram
The mechanism of action of the drug is based on the blocking of the enzyme Acetaldehyde Dehydrogenase, responsible for the oxidation of the most toxic intermediate product of alcohol disposal - acetaldehyde (vinegar aldehyde). It turns out that alcohol drunk by a person is not excreted from the body, and the process of its removal is "slowed down" at the level of a toxic substance, which causes a powerful poisoning, threatening serious consequences. The French pharmaceutical giant Sanofi, which has been producing it since the mid-60s of the last century under the name "Esperanal" - which comes from the Latin Espero - "hope" was the most active in promoting the new drug.
Indeed, there were great hopes for the prospects for the use of Disulfiram in broad medical practice. And it must be said, in many respects, their hopes have been justified, and today it is one of the leading means of maintaining sobriety. Disulfiram is produced under different trade names and is designed for various ways of clinical use - from daily taking of conventional tablets to implants, made for long periods, and how much is held in the body by disulfiram and other practical data you can find out in our clinic, contacting you in any way you like.
It's important to know the side effects
Adverse drug reactions (ADRs) to disulfiram treatment have been reported as isolated cases, but there are few systematic studies. In this study, we analyzed ADR's spontaneous reports to the Danish Drug Adverse Reaction Committee during 1968-1991. During this period, 154 ADR Disulfiram were recorded, mainly hepatic, neurological, skin and psychiatric reactions, in order of descending frequency. The safety of the disulfiram, estimated by the number and number of reported reactions, corresponds to an intermediate frequency of adverse reactions (1 in 200-2000 treatment). Over a 23-year period, 14 deaths were reported in Denmark, equivalent to 1 in 25,000 medical years; the main cause was toxicity to the liver. Reports from the WHO-affiliated Centre for International Drug Monitoring in Uppsala, Sweden, showed the same ADR profile, albeit with higher neurological and psychiatric levels and lower levels of liver reactions. The delay from the onset of treatment to The ADR varied from organ to organ. Hepatitis originated with a distinct peak after 2 months of treatment, skin reactions peaked after 2 weeks, and the frequency of neurological ADR increased with the duration of therapy. The link between skin reactions and hepatitis and nickel allergies, as well as the dose dependence of neuropathy, is discussed. The accompanying treatment with disulfiram affects the metabolism of some drugs and the dynamics of others, leading to a number of clinically important drug interactions. Disulfiram drug interactions are considered.
Alarming reactions can occur as a result of taking even a small amount of people who are treated with disulfiram. There is a pronounced depression, cardiovascular collapse, heart rhythm disorders, myocardial infarction, acute congestive heart failure, loss of consciousness, convulsions, as well as sudden and unexplained deaths.
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