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Disulfiram
Disulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals. Disulfiram is also being studied as a treatment for cocaine dependence, as it prevents the breakdown of dopamine (a neurotransmitter whose release is stimulated by cocaine); the excess dopamine results in increased anxiety, higher blood pressure, restlessness and other unpleasant symptoms. Several studies have reported that it has anti-protozoal activity as well. Research for possible disulfiram use in cancer therapy has been announced.
History
The drug's action was discovered by accident in 1948 by the researchers Erik Jacobsen, Jens Hald, and Keneth Ferguson at the Danish drug company Medicinalco. The substance was intended to provide a remedy for parasitic infestations; however, workers testing the substance on themselves reported severe symptoms after alcohol consumption.
Uses
Alcohol abuse
Under normal metabolism, alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to the harmless acetic acid. Disulfiram blocks this reaction at the intermediate stage by blocking the enzyme acetaldehyde dehydrogenase. After alcohol intake under the influence of disulfiram, the concentration of acetaldehyde in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. As acetaldehyde is one of the major causes of the symptoms of a "hangover" this produces immediate and severe negative reaction to alcohol intake. Some 5–10 minutes after alcohol intake, the patient may experience the effects of a severe hangover for a period of 30 minutes up to several hours. Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural fainting, and circulatory collapse.
Disulfiram should not be taken if alcohol has been consumed in the last 12 hours. There is no tolerance to disulfiram: the longer it is taken, the stronger its effects. As disulfiram is absorbed slowly through the digestive tract and eliminated slowly by the body the effects may last for up to two weeks after the initial intake; consequently, medical ethics dictate that patients must be fully informed about the disulfiram-alcohol reaction.
A nine-year study published in 2006 found that incorporation of supervised disulfiram and a related compound calcium carbimide into a comprehensive treatment program resulted in an abstinence rate of over 50%.
Antiprotozoal and anti-scabies
A study reported that it may be potentially useful in the treatment of Giardia infection. Another study found that it had activity against Trichomonas vaginalis which was resistant to the most common treatment, metronidazole.
It is also useful in the treatment of scabies as a combination drug of Benzyl benzoate/disulfiram.
Cancer
A patient with metastatic ocular melanoma was successfully treated by disulfiram with zinc gluconate. This can be explained as disulfiram creating complexes with metals (dithiocarbamate complexes) is proteasome inhibitor and can represent a new approach to proteasome inhibition. Clinical trials are recommended. There is ongoing clinical trial of disulfiram with copper gluconate against liver cancer in Utah (ClinicalTrials.gov Identifier: NCT00742911) and clinical trial of disulfiram as adjuvant against lung cancer in Israel (ClinicalTrials.gov Identifier: NCT00312819).
Side effects
The most common side effects (in the absence of alcohol) are drowsiness, headache, and a metallic or garlic taste in the mouth, though more severe side effects may occur. Tryptophol is a chemical compound that induces sleep in humans. It is formed in the liver after disulfiram treatment.
Cases of disulfiram neurotoxicity have also occurred, causing extrapyramidal and other symptoms.
Dosage
Disulfiram is supplied in 200 mg, 250 mg, and 500 mg tablets. The usual initial dose is 500 mg a day for 1 to 2 weeks, followed by a maintenance dose of 250 mg (range 125 mg–500 mg) per day. The total daily dosage should not exceed 500 mg.
Preparation
Disulfiram may be prepared from oxidation of sodium diethyldithiocarbamate with iodine:
2 NaS
2
CNEt
2
+ I
2
→ Et
2
NC(S)S-SC(S)NEt
2
+ 2 NaI (Et = C
2
H
5
)
Disulfiram. (2011, October 14).
In Wikipedia, The Free Encyclopedia.
Retrieved 11:26, October 17, 2011, from
http://en.wikipedia.org/w/index.php?title=Disulfiram&oldid=455564780
Cancer
Cancer /ˈkænsər/ ( listen), medically called a malignant neoplasm, is a term for a large group of different diseases. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous. Benign tumors do not grow uncontrollably, do not invade neighbouring tissues, and do not spread through the body.
Healthy cells control their own growth and will destroy themselves if they become unhealthy. Cell division is a complex process that is normally tightly regulated. Cancer happens when problems in the genes in a cell prevent these controls from working. These problems with genes may be from damage to the gene or may be inherited. Damage to genes can come from many sources inside or outside of the cell. Faults in two types of genes are especially important: oncogenes, which drive the growth of cancer cells, and tumor suppressor genes, which prevent cancer from developing.
Determining what causes cancer is complex, and it is often impossible to assign a specific cause for a specific cancer. Many things are known to increase the risk of cancer including tobacco use, infection, radiation, lack of physical activity, poor diet and obesity, and environmental pollutants. These can directly damage genes or combine with existing genetic faults within cells to cause the disease. A small percentage of cancers, approximately five to ten percent, are entirely hereditary.
Cancer can be detected in a number of ways, including the presence of certain signs and symptoms, screening tests, or medical imaging. Once a possible cancer is detected it is diagnosed by microscopic examination of a tissue sample. Cancer is usually treated with chemotherapy, radiation therapy and surgery. The chances of surviving the disease vary greatly by the type and location of the cancer and the extent of disease at the start of treatment. While cancer can affect people of all ages, and a few types of cancer are more common in children, the risk of developing cancer generally increases with age. In 2007, cancer caused about 13% of all human deaths worldwide (7.9 million). Rates are rising as more people live to an old age and as mass lifestyle changes occur in the developing world.
Cancer. (2011, October 9). In
Wikipedia, The Free Encyclopedia
. Retrieved 10:10, October 17, 2011, from
http://en.wikipedia.org/w/index.php?title=Cancer&oldid=454709980
INVESTMENTS IN EDUCATION DEVELOPMENT
INVESTMENTS IN EDUCATION DEVELOPMENT. Project OP VK CZ.1.07/2.3.00/20.0062. An inexpensive drug Antabuse as anticancer remedy: mechanism of action and clinical trials.