Effects Of Alcohol Withdrawal Research Articles

The effects of alcohol withdrawal and acute doses of alcohol on the acid-base balance in mice and rats

While respiratory alkalosis has been reported to occur in human alcoholics during the withdrawal period, and may causally contribute to the expression of the withdrawal syndrome, we found no evidence of this in either alcohol physically-dependent mice (DBA/2J) or rats (Sprague-Dawley) as reflected in blood pH, plasma pCO 2, or intracellular brain pH relative to pair-fed control (no alcohol) animals. The inhalation of atmospheres high in CO 2 (5% and 15%), which would be expected to reverse a respiratory alkalotic state, had no effect on the expression of the withdrawal syndrome in alcohol-dependent mice. These results indicate that a withdrawal syndrome of considerable intensity can develop in mice and rats in the absence of an alkalotic state.

Alcohol withdrawal seizures: Implications of kindling

The periodic administration of convulsive agents, even at doses or intensities that initially have no convulsive effect, can lead to a progressive and enduring increase in the susceptibility to subsequent convulsive stimulation. This kindling effect has contributed to the understanding of the convulsive effects of alcohol withdrawal in three ways. First, rats kindled by the periodic application of electroconvulsive shock, local brain stimulation, or pentylenetetrazol were found to be hypersusceptible to the convulsive effects of subsequent alcohol withdrawal, thus raising the possibility that some forms of electrical or pharmacological therapy can potentiate the alcohol withdrawal syndrome in humans. Second, the duration of seizures elicited in kindled rats has been used as a sensitive index of convulsive withdrawal effects; increases in the duration of kindled motor seizures and afterdischarges can be detected following the metabolism of a single intoxicating injection of ethanol. Third, it was suggested that the potentiation of the convulsive effects of alcohol exposure and withdrawal by prior episodes of alcohol withdrawal may reflect a kindling-like process rather than an increase in physical dependence.

Diazepam kinetics in acute alcohol withdrawal

We performed a within-subject comparison of the kinetics of diazepam given to 7 alcoholic subjects during acute alcohol withdrawal and again after detoxification. The initial rapid exponential decline of plasma diazepam concentrations (t1/2 alpha) was more rapid during (0.21 +/- 0.03 hr) than after withdrawal (0.44 +/- 0.14 hr, p less than 0.05). Terminal t1/2, clearance, and volumes of distribution changed in individual patients, but mean values did not change. Protein binding was less in patients (93.4 +/- 2.4%) than in healthy controls (97.0 +/- 1.0, p less than 0.05). The effects of alcohol withdrawal on diazepam disposition do not explain the high doses of diazepam commonly required to treat the withdrawal.

Effects of alcohol withdrawal and undernutrition on cannibalism of rat pups

Pregnant Long-Evans hooded rats were treated (po) with alcohol (4 or 6 g/kg/day) throughout pregnancy. Pair-fed and ad lib fed animals served as controls. Alcohol-treated and pair-fed animals did not differ in the incidence of cannibalism when tested within 24 hr of parturition, but all four groups cannibalized pups to a greater extent than did ad lib fed controls. On Day 2 of testing, alcohol-treated mothers continued to cannibalize pups whereas pair-fed and ad lib fed animals did not kill pups.

Alcohol withdrawal effects on brain serotonin in mice behaviorally attracted to alcohol.

Serotonin concentration in whole brain tissue of CF1 mice behaviorally attracted to a 3% alcohol solution was significantly depressed 48 hours after access to the solution was denied. Norepinephrine concentration was not affected.

The effect of alcohol withdrawal on electrolyte and acid-base balance

A metabolic balance study of 5–7 days' duration was carried out on 8 chronic alcoholic males during alcohol withdrawal; 5 nonalcoholic patients were used as controls. Four alcoholic subjects without liver damage showed significant weight gain and Na + retention. Of 4 alcoholics with liver damage, only one showed a comparable Na + retention, and none gained weight. The 5 controls were close to Na + balance, and 4 of them lost weight. There was no significant difference between groups with respect to K + balance. Blood and plasma volume were significantly higher in the alcohol withdrawal group than in the controls, and the urine specific gravity tended to rise appreciably during the first 2 days of alcohol withdrawal. The alcohol withdrawal group, but not the controls, showed evidence of systemic alkalosis, as indicated by elevation of arterial blood pH and urine pH, decreased urinary NH 4 and titratable acidity, and reduced serum K +. These findings are consistent with the hypotheses that (1) alcohol withdrawal results in a “rebound” increase in antidiuretic hormone activity, following prolonged suppression of ADH by continuous drinking, (2) increased aldosterone activity occurs during continuous drinking but is masked by the opposing effects of ethanol; it is suggested that when alcohol is withdrawn the aldosterone effect becomes evident.

The treatment of drug and alcohol withdrawal effects with thorazine.

A comparison is made between patients treated by other methods, and with chlorpromazine, who were suffering from severe acute alcoholic intoxication, post-intoxication withdrawal, delirium tremens and postdelirious agitation. Dosages and methods of administration are discussed, as are the side effects encountered. Chlorpromazine is found to be the drug of choice for these syndromes.