Chronic alcohol abuse

Abnormalities of the glycosylation of transferrin occur in the congenital disorders of glycosylation (Chapter 47) and in chronic alcohol abuse. Their detection by, for example, isoelectric focusing is used to help diagnose these conditions. 

The myopathy associated with chronic alcohol abuse has also been associated with increased free-radical activity (Martin and Peters, 1985) as have various other toxicity syndromes affecting muscle, such as cocaine toxity (Kloss et al., 1983). Little work appears to have been undertaken on the possible role of free radicals in the inflammatory myopathies, although, by analogy with other inflammatory disorders, this is likely to be an area worthy of further study. 

The Wernicke-Korsakoff syndrome follows years of chronic alcohol abuse. However, alcoholics who do not develop this condition typically display a range of other cognitive impairments (Grant et al., 1987). Deficits in performance have been... 

Some toxic effects are reversible. Everyone has been exposed to some agent, household ammonia for example, that produces irritation to the skin or eyes. Exposure ends and, sometimes perhaps with a delay, the irritation ends. Some readers have no doubt been poisoned on occasion by the ingestion of too much alcohol. The effects here also reverse. The time necessary for reversal can vary greatly depending upon the severity of the intoxication and certain physiological features of the person intoxicated. But most people also realize that chronic alcohol abuse can lead to a serious liver disorder, cirrhosis, which may not reverse even if alcohol intake ceases. This type of effect is irreversible or only very slowly reversible. It is important in making a toxicological evaluation to understand whether effects are reversible or irreversible, because one is obviously much more serious than the other. 

So-called peripheral neuropathies can result from excessive exposure to certain industrial solvents such as carbon disulfide (CS2, used in the rubber and rayon industries) and hexane (CgHn, once used in certain glues and cleaning fluids). Over-exposure to acrylamide, an important industrial chemical, and chronic alcohol abuse can also induce this effect. As the name implies, it involves attack of the chemical on and damage to axonal portions of neurons. Typical symptoms of peripheral neuropathies include weakness or numbness in the limbs, which are more or less reversible depending upon the specific agent and the intensity of exposure. 

Toxicologists nowadays take a broad view of developmental toxicity they consider not only structural but also functional abnormalities to qualify as adverse, as long as they were produced as a result of exposures incurred in utero. Thus, for example, the developmental effects of chronic alcohol abuse by pregnant women, known as fetal alcohol syndrome (FAS), are characterized not only by the presence of certain craniofacial abnormalities, but also by a variety of disabilities such as shortened attention span, speech disorders, and restlessness. Although fully expressed physical deformities included in FAS are associated with heavy drinking, debate continues on the level of alcohol consumption, if any, that is without these more subtle effects on behavior. 

Other important components of the initial evaluation include a medical evaluation including both a medical history and physical examination. This can identify medical consequences of substance abuse, such as liver impairment from chronic alcohol abuse or sinus complications from cocaine use, as well as reveal needle tracks from a variety of self-injection sites that might not be readily apparent to casual observation. 

Where patients are at risk of Wernicke s encephalopathy - for example, because of chronic alcohol abuse, hyperemesis gravidarum, or malnutrition - they should be given thiamine. In many countries no intravenous preparation of thiamine alone is available, and the compound preparations that are available are prone to cause anaphylactoid reactions, so they should be given by slow infusion, and with adequate facilities for resuscitation. A high potency preparation (Pabrinex ) that contains thiamine 250 mg in 10 ml with ascorbic acid, nicotinamide, pyridoxine and riboflavin, can be given by intravenous infusion over 10 min. 

Liver disease is the most common medical complication of alcohol abuse an estimated 15-30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Concurrent infection with hepatitis or C virus increases the risk of severe liver disease. 

Carbamazepine, chronic alcohol abuse, reserpine, sucralfate, molindon hyd rochloride, antacids containing calcium... 

Of 308 patients 73% had contraindications, risk factors, or intercurrent illnesses necessitating withdrawal of metformin (31) 19% had renal impairment, 25% heart failure, 6.5% respiratory insufficiency, and 1.3% hepatic impairment 51% had advanced coronary heart disease, 9.8% atrial fibrillation, 3.3% chronic alcohol abuse, 2% advanced peripheral arterial disease, and 0.7% were pregnant. 

Oral baclofen has also been used to reduce alcohol consumption in people who are chronic alcohol abusers.21,22 Apparently, relatively low doses of baclofen can reduce the cravings and desire for alcohol consumption via the effects of this drug on CNS GABA receptors.21 Future studies will help clarify the role of this drug in treating chronic alcoholism. 

Delirium tremens usually arises in chronic alcohol abusers. The clinical features may include hallucinations, intense fear, sleeplessness, restlessness, agitation, delirium, and sometimes grand mal convulsions. In addition, tachycardia, hypotension, and clover-shaped ST changes in the electrocardiogram are evident. 

ALCOHOLISM A disease that results in chronic alcohol abuse. Alcoholism can cause early death from complications to the brain, liver, and heart. 

There are many drugs that increase the rate of the liver s metabolism. More commonly used medications that fall into this category include rifampin, which is used to treat tuberculosis, and dilantin, phenytoin, and carbamazepine, which are medications commonly used to treat seizures and epilepsy. Chronic alcohol abuse also speeds up the metabolism of the liver. Since all of these substances cause the liver to break down methadone faster then it normally would, one way to correct the problem would be to increase the dose of methadone or break down the dose into several smaller doses given throughout the day. This should only be done on a physician s advice. 

Liver cirrhosis is among the top 10 causes of death in the Western world. The disease occurs after chronic damage to hepatic cells, mainly hepatocytes, which can be caused by viral hepatitis, chronic alcohol abuse or toxic injury, biliary disease, and metabolic liver disorders [64], Liver cirrhosis is characterized by an abnormal deposition of connective tissue in the liver, which hampers the normal functions of the liver. Other features of the disease are general tissue damage, chronic inflammation, and the conversion of normal liver architecture into structurally abnormal nodules. Secondary to these anatomical changes are disturbances in the liver function and in the hemodynamics leading to portal hypertension and intrahepatic shunting [39, 64, 103],... 

In chronic alcohol abuse, mainly two organs are damaged ... 

Chronic alcohol abuse is an expression of true dependence. Thus, therapy of this addiction is dif cult and frequently without success. There is no pharmacotherapeutic silver bullet (the NMDA receptor antagonist acamprosate may be worth trying). Above all, psychotherapeutic care, a change in milieu, and supportive treatment with benzodiazepines are important. 

Myoclonus due to maprotiline has been reported (13). Further neuromuscular symptoms that have been reported with maprotiline include cerebellar ataxia in a 54-year-old man with a history of unipolar depression and chronic alcohol abuse who was taking maprotiline 200 mg/day (14). The question of whether his history of alcohol abuse contributed by sensitizing his cerebellum to maprotiline-induced ataxia was unresolved. 

The two main memory disorders are amnesia and aphasia. Amnesia is a partial or total loss of memory caused by emotional trauma, disease, or brain injury (usually due to head trauma, surgical accidents, or chronic alcohol abuse). Memory loss can occur for events just prior to the amnesia-causing incident (retrograde amnesia), or for events occurring after the incident (anterograde amnesia). In severe cases of anterograde amnesia, the person may be unable to form n memories, although recall of material learned before amnesia s onset is usually unaffected. Many cases of amnesia (even severe) are temporary, so that the person recovers his or her memory. 

Fig. 21.15 Pericellular trabecular fibrosis showing a wire mesh pattern (so-called chicken-wire fibrosis) due to chronic alcohol abuse (Sirius red)...

Central venules only contain a small amount of collagen, with the result that in this form of fibrosis, perivenous sinusoids are always involved as well. A typical example is perivenular fibrosis in chronic alcohol abuse, (s. fig. 21.16) Centrolobular fibrosis may also be detectable in healed viral hepatitis or following slight liver damage (e.g. Meulengracht s disease). Central hyaline sclerosis, which is due to chronic alcohol abuse with intermittently recurring alcohol hepatitis, is known to be a particularly severe form of fibrosis, (s. p. 526)... 

Budd-Chiari syndrome chronic alcohol abuse chronic blood congestion... 

Fig. 21.16 Perivenular and perisinusoidal fine-meshed fibrosis and discreet cellular inflammatory reaction as a result of chronic alcohol abuse (CV = central vein) (Ladewig)...

A rise in the NADH/NAD ratio and the associated increase in the redox potential as well as the formation of acetaldehyde result in a variety of metabolic disturbances in the hepatocellular oxidation processes, so that pathophysiological consequences can be observed. This large variety of alcohol-induced metabolic disturbances is responsible for many situations of clinical importance, and thus acute and chronic alcohol abuse will eventually result in additional metabolic complications, (s. tab. 28.2)... 

De Feo, T.M., Fargion, S., Duca, L., Mattioli, M., Cappellini, M.D., Sampietro, M., Cesana, B.M., Fiorelli, G. Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron. Hepatology 1999 29 658-663... 

Parlesak, A., Schafer, C., Schiitz, T., Bode, J.C., Bode, C. Increased intestinal permeabihty to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced hver disease. J. Hepatol. 2000 32 742—747... 

Hypoglycaemia is a rare event. It is nearly always due to reduced gluconeogenesis, particularly following loss of parenchyma (usually >80%). Chronic alcohol abuse or acute alcohol intoxication can lead to hypoglycaemia. (s. p. 522)... 

Peptic ulcer is not cirrhosis-related. Duodenal ulcers are more common than gastric ulcers. Frequency of peptic ulceration in cirrhotic patients is about 8-10%, although 60—70% of these cases are as)miptomatic. Gastric ulcers heal more slowly and recur more frequently than in non-drrhotic patients. (55) This condition may be caused by chronic alcohol abuse, portal hypertension or Helicobacter pylori infection (40—50%, with elevated gastrin in the serum). (134, 205) Mallory-Weiss syndrome is often associated with cirrhosis, but there is in fact no causal relationship between the two. Gastroparesis with delayed gastric emptying is frequently observed. (190)... 

Despite its favorable safety profile, it cannot be assumed that thiamine is completely innocuous. Thiamine hydrochloride is routinely given to patients with Wernicke s encephalopathy or malnourished states (such as malabsorption, beri-beri, cancer, AIDS, and chronic alcohol abuse). Systemic reactions are rare but deaths can occur. 

Taracha E, Flabrat B, Lehner M, Wislowska A, Woronowicz BT, Bogulas M, Charewicz J, Markuszewski C, Plaznik A. Alanine ami-nopeptidase activity in urine a new marker of chronic alcohol abuse Alcohol Clin Exp Res. 2004 28 729-35. 

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