Disulfiram effect

Alcohol or substances with disulfiram effect (e.g. mushrooms, griseofulvin,sulfonyl urea)... 

I These cephalosporins contain the methylthiotetrazole side chain and can cause hypopro-thrombinemia and bleeding problems as well as a disulfiram effect, that is, an intolerance to ingested ethanol. 

McCance-Katz EF, Kosten TR, Jatlow P (1998) Disulfiram effects on acute cocaine administration. Drug Alcohol Depend 52 27-39... 

Kharasch, E.D., D.C. Hankins, C. Jubert, R.E. Thummel, and J.K. Taraday (1999). Lack of singledose disulfiram effects on cytochrome P-450 2C9, 2C19,2D6, and 3A4 activities Evidence for specificity toward P-450 2E1. Drug Metab. Dispos. 27, 717-723. 

Chivers CP. Disulfiram effect from inhalation of dimetiiylformamide. Lancet ( 91 ) i, 331. 

McCance-Katz EF, Gruber VA, Beatty G, Liun P, Ma Q, Diffancesco R, et al. Interaction of disuffiram with antiretroviral medications efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism. Am J Addict 2013 23(2) 137-44. 

Procarbazine causes myelosuppression, hypnotic and other effects on the central nervous system, e.g., vivid nightmares. Also, procarbazine causes a disulfiram like syndrome on ingestion of ethanol. 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

One fascinating aspect of the effect of the genetic polymorphisms described earlier is that acculturation can partially overcome the protective factor, and Asian groups born in North America may have only partial protection (Goldman 1993 Tu and Israel 1995). In individuals who consume small amounts of alcohol over time, the aversive effects diminish, an effect similar to that described in clinical reports of patients who developed a resistance to the effects of disulfiram. 

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

Disulfiram is usually given orally. Because there is an increased risk of side effects and toxic hazards as the dosage is increased, the daily dosage prescribed in the United States has been limited to 250—500 mg/day. However, efforts to titrate the dosage of disulfiram in relation to a challenge dose of ethanol indicated that some patients require in excess of 1 g/day of disulfiram to reach blood levels sufficient to produce a DER (Brewer 1984). 

Anton RF, Pettinati H, Zweben A, et al A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24 421 28, 2004 Aragon CM, Stotland LM, Amit Z Studies on ethanol-brain catalase interaction evidence for central ethanol oxidation. Alcohol Clin Exp Res 15 165-169, 1991 Arizzi MN, Correa M, Betz AJ, et al Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats studies with low and high rate operant schedules. Behav Brain Res 147 203—210, 2003 Azrin NH, Sisson RW, Meyers R, et al Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psychiatry 13 105—112, 1982 Babor TF, Kranzler HR, Lauerman RL Social drinking as a health and psychosocial risk factor Anstie s limit revisited, in Recent Developments in Alcoholism, Vol 5. Edited by Galanter M. New York, Plenum, 1987, pp 373 02... 

Brewer C How effective is the standard dose of disulfiram a review of the alcohol-disulfiram reaction in practice. Br J Psychiatry 144 200—202, 1984... 

Chester JA, Cunningham CL GABA(A) receptor modulation of the rewarding and aversive effects of ethanol. Alcohol 26 131—143, 2002 Chick J Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Saf 20 427 35, 1999... 

Azrin NH, Sisson RW, Meyers R, et al Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psy 13 105-112, 1982 Bickel WK, Amass L, Higgins ST, et al Effects of adding behavioral treatment to opioid detoxification with buprenorphine. J Consult Clin Psychol 65 803—810, 1997 Bien TH, Miller WR, Tonigan JS Brief interventions for alcohol prohlems a review. Addiction 88 315-335, 1993... 

Bartonicek V, Teisinger J. 1962. Effect of tetraethyl thiram disulphide (disulfiram) on metabolism of trichloroethylene in man. Br JIndMed 19 216-221. 

MacDonnell. M.F and Fessock, L. Some effects of ethanol, amphetamine, disulfiram and p-CPA on seizing of prey in feline predatory attack and on associated motor pathways. Q J Stud Ale 33 437-450, 1972. 

Otherwise, if benzodiazepines are combined with disulfiram the pharmacologic effect may be greater than expected, and the dose of benzodiazepine may need to be lowered. 

Disulfiram decreases the clearance of cocaine from the body may see increased or prolonged cocaine effects with this combination. 

Disulfiram works by irreversibly blocking the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol, resulting in increased blood levels of the toxic metabolite acetaldehyde. As levels of acetaldehyde increase, the patient experiences decreased blood pressure, increased heart rate, chest pain, palpitations, dizziness, flushing, sweating, weakness, nausea and vomiting, headache, shortness of breath, blurred vision, and syncope. These effects are commonly referred to as the disulfiram-ethanol reaction. Their severity increases with the amount of alcohol that is consumed, and they may warrant emergency treatment. Disulfiram is contraindicated in patients who have cardiovascular or cerebrovascular disease, because the hypotensive effects of the disulfiram-alcohol reaction could be fatal in such patients or in combination with antihypertensive medications. Disulfiram is relatively contraindicated in patients with diabetes, hypothyroidism, epilepsy, liver disease, and kidney disease as well as impulsively suicidal patients. 

The therapeutic dose of acamprosate is 666 mg orally three times daily, and it is supplied as a 333 mg tablet. It can be started at the full dose in most patients without titration. It differs from disulfiram and naltrexone in that it is excreted by the kidneys without liver metabolism. Consequently, it is contraindicated in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/minute), and dose reduction is necessary when the creatinine clearance is between 30 and 50 mL/minute. The most common side effects are gastrointestinal and include nausea and diarrhea. Rates of suicidal thoughts were also increased in patients treated for 1 year with acamprosate (2.4%) versus placebo (0.8%). If necessary the total daily dose maybe decreased by 1 to 3 tablets (333-999 mg) per day to alleviate side effects. 

Metronidazole maybe administered orally as a single 2-g dose or 500 mg twice daily for 7 days.17 Pregnant women should be prescribed the single dose of metronidazole. Cure rates are greater than 90% when metronidazole is administered as either a single 2-g dose or a 7-day regimen. Possible adverse effects include an unpleasant metallic taste, reversible neutropenia, urticaria, rash, flushing, dry mouth, darkened urine, and a disulfiram-like reaction. 

Bourdelat-Parks B., Anderson G., Donaldson Z. et al. (2005). Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice. Psychopharmacol. (Berl). 183, 72-80. 

Patients taking metronidazole should be instructed to avoid alcohol ingestion during therapy and for 1 to 2 days after completion of therapy because of a possible disulfiram-like effect. 

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