Pathophysiology of delirious states.

MHPG concentration in CSF, urinary excretion of NA and A as well as activity of serum DBH were significantly elevated during alcohol delirium as compared to the recovery period. Urinary DA and HVA in CSF did not show any constant change. One single dosage of clozapine (100 mg orally) induces higher urinary NA and A excretion. There is a time course of clozapine action. MHPG in rat brain a single dosage (50 mg/kg) is elevated; after repeated administration (11 days) a decrease is observed. After 10 days of treatment with clozapine (300 mg/day) a decrease of MHPG in CSF can be seen. It is hypothesized that there is a relationship between delirious states and increases central NA turnover.

[Cyclic adenosine monophosphate (3'5' cAMP) in the alcohol withdrawal syndrome. Clinico-pathogenetic perspectives]. / L'adenosinmonofosfato ciclico (3'5' AMP-c) nella sindrome da astinenza alcoolica (S.A.A.). Prospettive clinico-patogenetiche.

The cyclic adenosine monophosphate (AMP-c) excreted in the urine over a 24 hour period was systematically measured in 40 patients suffering from alcohol withdrawal syndrome (AWS) in varying degrees from slight to delirium tremens. In almost all patients the level of excreted AMP-c was high bul returned to normal when the clinical picture together with arterial pressure and cardiac frequency, was normalised. This shows the primary importance of the central sympathetic-adrenergic system in the pathogenesis of AWS and the value of monitoring urinary AMP-c excretion during the syndrome.

[Is serotonin implicated in the pathogenesis of the alcohol abstinence syndrome?]. / E la serotonina implicata nella patogenesi della sindrome da astinenza alcoolica?

5-Hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-hydroxytryptamine or serotonin, excreted in the urine over a 24 hour period was systematically measured in 35 patients with alcohol withdrawal syndrome (AWS). The level of excreted urinary 5-HIAA ac. was high in only a few patients. The pathogenic mechanisms involved are discussed and though the role of serotonin in the pathogenesis of AWS seems of secondary importance, some 5-hydroxytryptamine methyl analogues may have a major role in the pathogenesis of hallucinations caused by alcohol withdrawal.

[Beta-blockers in the complex treatment of alcoholic delirium]. / Beta-blokatory v kompleksnoi terapii alkogol'nogo deliriia.

Seventy-two patients with acute alcoholic delirium were examined cliniconeurophysiologically. The Athena scale, neurovegetative indices as well as those of adrenaline, noradrenaline, dopamine, and DOPA excretion were used for delirium gravity estimation. Proceeding from these data an attempt was made to use the beta-blocking agent obsidan for combined delirium treatment. The data obtained allow using the pathogenetic drugs for differentiated search of delirium treatment. Application of obsidan, an agent blocking hyperactivity of central adrenergic mechanisms in abortive and typical delirium promoted the removal of affective disorders, normalized hemodynamics and prevented early exhaustion of adrenergic mechanisms. Thus, obsidan produces favorable therapeutic effects when used in a complex of measures for alcoholic delirium treatment.

Impaired water excretion and elevated plasma vasopressin in patients with alcohol-withdrawal symptoms.

Reports describing the fluid balance status of alcoholics in withdrawal are varied, and conflicting. We examined this question by recording values for a variety of parameters in response to a standard water load test. Compared with age and sex matched healthy volunteers (n = 14), alcoholics in withdrawal (n = 17) exhibited lower cumulative urine output (p = 0.0001), higher minimum urine osmolality (p = 0.0001), lower serum sodium (p = 0.0024 before loading) and elevated plasma arginine vasopressin levels (p = 0.0045 before loading). We believe that these findings are best explained by a resetting of osmoreceptors, a supposition in keeping with contemporary views on the pathogenesis of alcohol dependence and withdrawal. This additional evidence of an antidiuretic state in alcohol withdrawal leads us to question the practice of fluid supplementation in its management and we suggest that this policy be revised.

Excretion of beta-carbolines harman and norharman in 24-hour urine of chronic alcoholics during withdrawal and controlled abstinence.

Animal experiments suggest that endogenous substances that could result from the interaction between neurotransmitters (dopamine and indoleamines) and ethanol and its metabolite acetaldehyde might be involved in the pathogenesis and maintenance of alcohol dependence. Therefore, aromatic beta-carbolines (norharman and harman) were investigated repeatedly in 24-hr urine of 13 male severe alcoholics without any psychiatric comorbidity during a controlled inpatient abstention program of up to 8 weeks. Harman excretion was approximately 2-fold above levels in control subjects, with a steady decline after 3 weeks of abstinence and lower levels in patients with a longer duration of alcohol dependence. Severity of withdrawal symptoms and actual feelings of anxiety/depression were negatively associated with urinary harman excretion. Positive associations could be established with daily ethanol consumption the month before admission and the score on the scale "reward dependence" according to Cloninger's Tridimensional Personality Questionnaire. Moreover, patients without alcohol-dependent first-degree relatives and higher "reward dependence" exhibited an increased excretion of harman. Therefore, harman levels might characterize a distinct subgroup of alcoholic patients, who in part resemble the so-called type l alcoholics of Cloninger. However, this awaits further study in a larger number of individuals. In contrast, norharman excretion was elevated up to 6-fold, compared with nonalcoholics over 6 to 8 weeks of controlled abstention. No correlations to demographic or clinical variables could be observed. Therefore, increased norharman levels might be proposed as a "residual marker" or a trait variable. Whether the observed changes are specific markers of at least certain aspects of alcoholism or dependence remain to be elucidated.