Ethanol renal effects

In most cases the mechanism is not known. Stimulators of vasopressin secretion include vincristine, cyclophosphamide, tricyclic antidepressants, nicotine, epinephrine, and high doses of morphine. Lithium, which inhibits the renal effects of vasopressin, also enhances vasopressin secretion. Inhibitors of vasopressin secretion include ethanol, phenytoin, low doses of morphine, glucocorticoids, fluphenazine, haloperidol, promethazine, oxilorphan, and butorphanol. Carba-mazepine has a renal action to produce antidiuresis in patients with central diabetes insipidus but actually inhibits vasopressin secretion via a central action. 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

For patients who have ingested more than 30 ml of (pure) methanol or ethylene glycol, dialysis is recommended, and haemodialysis is more effective than peritoneal dialysis. Dialysis both removes the alcohols and their metabolites, and corrects the renal and metabolic disturbances and so is the preferred treatment in severe poisoning. The maintenance dose of ethanol required may be tripled during haemodialysis as ethanol is also removed. Early treatment is indicated if ethylene glycol concentrations are above 20 mg/100 ml (200 mg/1), if the arterial pH is below 7.3, if serum bicarbonate concentrations are less than 20 mM/1, and when there are oxalate crystals in the urine. 

Ethanol is a diuretic. This effect may be caused by its ability to inhibit secretion of antidiuretic hormone from the posterior pituitary, which leads to a reduction in renal tubular water reabsorption. The large amount of fluid normally consumed with ethanol also contributes to increased urine production. 

Glyburide has few adverse effects other than its potential for causing hypoglycemia. Flushing has rarely been reported after ethanol ingestion, and the compound slightly enhances free water clearance. Glyburide is contraindicated in the presence of hepatic impairment and in patients with renal insufficiency. 

TAC of blood plasma in rats fed an ethanol-supplemented diet increases, although ethanol is known to induce oxidative stress. The effect is due to ethanol-induced purine degradation and increase in the level of uric acid (G2). TAC of blood plasma in critically ill patients with renal dysfunction is augmented, again due to increase in uric acid level (Ml). Caloric restriction, a procedure known to improve the redox status and prolong the life span of mammals, decreases TAC of rat serum (C12). 

Treatment should include correction of metabolic acidosis, inhibition of ethylene glycol metabolism and if necessary, extracorporeal elimination of the parent alcohol and metabolites. Acidemia likely increases tissue penetration of toxic metabolites and hinders renal clearance. Although evidence is lacking, bicarbonate administration should be given to correct acidemia. Although more expensive, fomepizole is preferred to ethanol for ADH inhibition due to proven efficacy, predictable pharmacokinetics, and lack of adverse effects [105]. Inhibition of ADH with fomepizole prevents formation of toxic metabolites and renal injury, and improves add-base status [106]. Elimination half-life of ethylene glycol with fomepizole in patients with preserved renal function is approximately 20 hours [107]. Pyridoxine and thiamine should be administered to promote glyoxyhc add conversion less toxic metabolites than oxalate [108]. 

Usual measures for decontamination (ipecac/lavage, activated charcoal, cathartics) are recommended within 2h of ingestion. Renal and hepatic function should be monitored and supported. If acidosis occurs, treatment should begin with 1 or 2 mEq kg (for children ImEqkg ) of sodium bicarbonate intravenously, repeated every 1 or 2 h as needed. Hemodialysis may be necessary for severe acid/base disturbances or renal failure. Treatment with ethanol has been effective in animals, but efficacy data for humans are not available. 

Carbon tetrachloride, which has been used in fire extinguishers as a fire suppressant, is a known renal toxin. In a study of people exposed to carbon tetrachloride vapors during fire fighting activities, it was found that those individuals with histories of alcohol abuse experience greater nephrotoxic effects (including renal failure) than those who do not abuse alcohol. The authors of the study conclude that ethanol potentiates the nephrotoxic effects of carbon tetrachloride. 11 This is an example of a potentiated effect being observed when exposure is to a mixture of a lipophile (carbon tetrachloride Kow = 2.83) and a hydrophile (ethanol Kow = -0.32). 

The renal toxicity of carbon tetrachloride is also potentiated by isopropanol (IPA), as well as by ethanol. Workers in a chemical packaging plant were exposed to a mixture of vapors of carbon tetrachloride and IPA when the spacing between two packaging lines (one for each solvent) was small enough to create a mixed vapor atmosphere. Renal failure developed in 4 of the 14 workers so exposed. The authors of the study attribute the potentiating effect of IPA on carbon tetrachloride to acetone, a metabolite of IPA. They contrast this with the potentiation of ethanol on carbon tetrachloride, where it is the contaminant (ethanol) and not the metabolite that is the cause of the potentiation. P21 This is a further example of a potentiated effect being observed from a mixture of a lipophile (carbon tetrachloride, Kqw = 2.83) and a hydrophile (acetone, Kqw = -0.24). 

Although both ethanol and tobacco smoke are renal toxins, a laboratory animal study demonstrated that the combination of the two produced nephrotoxic effects different from either one alone. P9]... 

Associated with renal dysfunction (4 PGs) and hypoglycemia. Many drug interactions (ethanol T GI bleeding, T effects of sulfonylurea hypoglycemics, and warfarin, 4 effects of uricosurics). 

Mineralocortioids and glucocorticoids inhibition of AVP release—ethanol and phenytoin reduction of AVP effect on renal tubules and diuresis—lithium... 

The major receptor-mediated adverse effect is water intoxication, which can occur with desmopressin or vasopressin. Many drugs, including carbamazepine, chlorpropamide, morphine, tricyclic antidepressants and NSAIDs, can potentiate the antidiuretic effects of these peptides, while lithium, demeclocycline and ethanol can attenuate the antidiuretic response to desmopressin. Desmopressin and vasopressin should be used cautiously when a rapid increase in extracellular water may impose risks (e.g., in angina, hypertension, and heart failure) and should not be used in patients with acute renal failure. Patients receiving desmopressin to maintain hemostasis should be... 

I. Mechanism of toxicity. Carbon tetrachloride and chloroform are CNS depressants and potent hepatic and renal toxins. They may also increase the sensitivity of the myocardium to arrhythmogenic effects of catecholamines. The mechanism of hepatic and renal toxicity is thought to be a result of a toxic free-radical intermediate of cytochrome P-450 metabolism. (Bioactivation of CCI4 has become a model for chemical toxicity induced by free radicals.) Chronic use of metabolic enzyme inducers such as phenobarbital and ethanol increases the toxicity of carbon tetrachloride. Carbon tetrachloride is a known animal and suspected human carcinogen. Chloroform is embryotoxic and an animal carcincogen. 

Diethylene glycol Highly nephrotoxic similar to ethylene glycol. Renal failure, coma, acidosis, and death have been reported In 5 patients with extensive burn Injuries after repeated dermal application. Vomiting, diarrhea, renal failure, metabolic acidosis, hepatitis, pancreatitis, coma, and death reported after Ingestion. Calcium oxalate crystals have been seen In animal studies. Molecular weight Is 106. Ethanol and fomepizole may be effective. 

Paul MD, Parfrey PS, Smart M, Gault H. The effect of ethanol on serum cycloi rine A levels in renal transplant patients. AmJKidney Dis ( 9%7) 10,133-5. 

In rats orally administered single doses of 50 or 100 mg/ kg of water or ethanol extracts of pill-bearing spurge daily, a time-dependent increase in urine output was observed. The water extract increased the urine excretion of sodium, potassium, and bicarbonate. In contrast, the ethanol extract increased the excretion of bicarbonate, decreased the loss of potassium, and had little effect on renal removal of sodium. The activity of pill-bearing spurge was noted as similar to the drug acetazolamide (Johnson et al. 1999). 

Angervall L, Bengtsson U, Lehmann L (1972) Renal diseases caused by drugs. In Samter M, Parker CW (eds) International encyclopedia of pharmacology and therapeutics. Sect 75 Hypersensitivity to drugs. Pergamon, Oxford Atkinson JP, Sullivan TJ, Kelly JP, Parker CW (1977) Stimulation by alcohols of cAMP metabolism in human lymphocytes. Possible role of cAMP in the anti-inflammatory effects of ethanol. J Clin Invest 60 284-294... 

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