However, these lower doses may therefore produce less chronic toxicity and provide a harm minimization approach to chronic alcoholism. It is, in essence, the antithesis of a disulfiram approach which tries to increase the buildup of acetaldehyde resulting in positive punishment for the patient. Compliance, and adherence, is a substantial problem in disulfiram-based approaches. Disulfiram also has a considerably longer half-life than that of fomepizole, requiring the person to not drink ethanol in order to avoid severe effects. If the person is not adequately managed on a benzodiazepine, barbiturate, acamprosate, or another GABAA receptor agonist, the alcohol withdrawal syndrome, and its attendant, life-threatening risk of delirium tremens "DT", may occur. Disulfiram treatment should never be initiated until the risk of DT has been evaluated, and mitigated appropriately. Fomepizole treatment may be initiated while the DT de-titration sequence is still being calibrated based upon the persons withdrawal symptoms and psychological health. Adverse effects
Common side effects associated with fomepizole use include headache and nausea. Kinetics
Absorption and distribution
Fomepizole distributes rapidly into total body water. The volume of distribution is between 0.6 and 1.02 L/kg. The therapeutic concentration is from 8.2 to 24.6 mg (100 to 300 micromoles) per liter. Peak concentration following single oral doses of 7 to 50 mg/kg of body weight occurred in 1 to 2 hours. The half-life varies with dose, so has not been calculated. Metabolism and elimination
Hepatic; the primary metabolite is 4-carboxypyrazole (about 80 to 85% of an administered dose).
It is still available to physicians for patients in emergency situations that are life-threatening or require hospitalization.Prucalopride (brand name Resolor) is a current
drug approved for use in the EU since October 15, 2009, in Canada (brand name Resotran) since December 7, 2011, and in the United States since December 2018. Chloride channel activators
Lubiprostone is used in the management of chronic idiopathic constipation and irritable bowel syndrome. It causes the intestines to produce a chloride-rich fluid secretion that softens the stool, increases motility, and promotes spontaneous bowel movements (SBM). Comparison of available agents
Effectiveness
For adults, a randomized controlled trial found PEG (MiraLax or GlycoLax) 17 grams once per day to be superior to tegaserod at 6 mg twice per day. A randomized controlled trial found greater improvement from two sachets (26 grams) of PEG versus two sachets (20 grams) of lactulose. 17 grams per day of PEG has been effective and safe in a randomized controlled trial for six months. Another randomized controlled trial found no difference between sorbitol and lactulose.For children, PEG was found to be more effective than lactulose. Problems with use
Laxative abuse
Some of the less significant adverse effects of laxative abuse include dehydration (which causes tremors, weakness, fainting, blurred vision, kidney damage), low blood pressure, fast heart rate, postural dizziness and fainting; however, laxative abuse can lead to potentially fatal acid-base and electrolyte imbalances. For example, severe hypokalaemia has been associated with distal renal tubular acidosis from laxative abuse. Metabolic alkalosis is the most common acid-base imbalance observed.