Ethanol chronic ingestion

Barbiturates Carbamazepine Ethanol, chronic ingestion Phenytoin... 

In adults, ethanol is metabolized at about 10 to 15 mL/hour. Since metabolism of ethanol is slow, ingestion must be controlled to prevent accumulation and intoxication. There is little evidence that chronic ingestion of ethanol leads to a significant induction of alcohol dehydrogenase, even in heavy drinkers. 

The rates of metabolism are also impaired in vitamin deficiency states (especially vitamin A, vitamin B, C and E). Starvation in mice leads to decrease in the rates of metabolism of certain drugs like pethidine, acetanilide, hexobarbitone etc. Ethanol increases the hepatic content of monooxygenase enzymes and cytochrome P450 on chronic ingestion. 

How does chronic ingestion of ethanol lead to the development of a fatty liver, if you are told that ethanol stimulates the activity of phosphatidic acid phosphatase ... 

Depending upon the size and time of the dose, ethanol may have two opposing effect on the biotransformation of VOCs. Intake of ethanol (short-term) in moderate amounts has a marked inhibitory effect on the biotransformation of several VOCs such as toluene, TCE, styrene, and w-xylene. However, chronic ingestion of alcohol induces the liver P450s. 

Most, if not all, of the tissues and organs in the body are adversely affected by chronic ingestion of excessive amounts of alcohol, including the liver, pancreas, heart, reproductive organs, central nervous system, and the fetus. Some of the effects of alcohol ingestion, such as the psychotropic effects on the brain or inhibition of vitamin transport, are direct effects caused by ethanol itself. However, many of the acute and chronic pathophysiologic effects of alcohol relate to the pathways of ethanol metabolism (see Chapter 25). 

Chronic ingestion of ethanol has increased the content of MEOS, the microsomal ethanol oxidizing system, in Al Martini s liver. MEOS is a cytochrome P450 enzyme that catalyzes the conversion of ethanol, NADPH and O2 to acetaldehyde, NADP, and 2 H2O (see Chapter 9). The adjective microsomal is a term derived from experimental cell biology that is sometimes used for processes occurring in the ER. When cells are lysed in the laboratory, the ER is fragmented into vesicles called microsomes, which can be isolated by centrifugation. Microsomes, as such, are not actually present in cells. 

Ethanol Ethanol (OES 1000 ppm 8h TWA) has well-known effects on the CNS and can cause irritation. Although metabolised to acetaldehyde and acetate, ethanol appears to have little ability to cause chronic toxic effects at exposure levels likely to be encountered in reasonable industrial and laboratory use. It should be noted that ethanol may compete with other substances present in the workplace atmosphere for the oxidative enzyme systems involved in this metabolism, thereby inhibiting their metabolism or excretion and increasing their toxic effects. This may occur with a number of solvents including trichloroethylene, xylene, benzene and dimethylformamide. The presence of denaturants (e.g. methanol, pyridines) greatly increases the toxicity of ethanol by ingestion and may also present a hazard by the inhalation route. 

Chronic excessive ingestion of ethanol causes progressive liver damage because both ethanol and its metabolic products are direct hepatotoxins. 

Chronic ethanol use increases the risk of hepatotoxicity when acetaminophen is used in high doses however, acute ingestion of alcohol along with an acetaminophen overdose decreases the toxicity of acetaminophen. 

Blagoeva, et al. DNA alterations in rat organs after chronic exposure to cigarette smoke and/or ethanol ingestion. 

VLDLs are produced in the liver (Figure 18.17). They are composed predominantly of triacylglycerol, and their function is to carry this lipid from the liver to the peripheral tissues. There, the triacylglycerol is degraded by lipoprotein lipase, as discussed for chylomicrons (see p. 226). [Note "Fatty liver" (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic triacylglycerol synthesis and the secretion of VLDL. Such conditions include obesity, uncontrolled diabetes mellitus, and chronic ethanol ingestion.]... 

What are the major acute toxicological effects of ethanol How is ethanol exposure usually measured or expressed What is a particular chronic toxicological effect of long-term ethanol ingestion ... 

Hepatic Fibrosis/Cirrhosis Fibrosis usually results from chronic inflammation which can be the result of continuous exposure to a variety of hepatotoxic chemicals such as organic arscnicals, vinyl chloride, or high doses of vitamin A (Zimmerman, 1999), chronic ethanol ingestion and nonalcoholic fatty liver disease. Fibrosis usually occurs around the portal area, in the space of Disse, and around the central veins. This results in loss of liver architecture and function. The hepatocytes are replaced with fibrous material and thus there is hepatocyte loss. Periportal fibrosis may lead to portal hypertension. 

Alcohol abuse can predispose to paracetamol hepatotoxicity (84-91), even in moderate social drinkers who take therapeutic or modestly excessive doses (92), and there have been anecdotal reports of severe hepatotoxicity in chronic ethanol abusers after ingestion of 4 g/day (93). Alcoholics are more likely to exceed the recommended dosage of paracetamol and consequently may be at higher risk of hepatotoxicity than non-alcoholics (91,94). 

Chronic ethanol ingestion has also been shown to produce liver damage, which can eventually lead to cirrhosis of the liver and possibly death. Signs include enlarged liver, elevated serum enzymes, and jaundice. 

The mainstay of medical treatment of patients with ethanol toxicity is supportive care. In general, a conservative approach is recommended for ethanol intoxication. Supportive therapy for overdose may include treatment for respiratory depression, hypotension, and altered glucose or thiamine levels. If the ingestion occurred within one hour of presentation, placing a nasogastric tube and evacuating the stomach contents can prove helpful. In patients with chronic ethanol abuse, therapy may include administration of thiamine to prevent neurologic injury. The administration of medications to cause emesis is not recommended because of the rapid onset of CNS depression as well as aspiration risks. 

Chronic ethanol exposure by ingestion of alcoholic beverages produces widespread toxicity, ranging from liver and nervous system damage to reproductive impairment and birth defects. People are not likely to be exposed orally to ethanol alone when used as a fuel additive, and systemic effects of chronic exposure to ethanol by respiratory and dermal uptake would be negligible. 

Results of chronic MTBE exposure studies are the most widely available of all studies on the ether-like fuel oxygenates (MTBE, ETBE, TAME, DIPE). Evidence from animal bioassays demonstrates that long-term, high-level exposures to MTBE by either ingestion or inhalation cause cancer in rodents. Inhalation exposure to MTBE produced an increased incidence of renal and testicular tumors in male rats and liver tumors in mice. Oral administration of MTBE produced an increased incidence of lymphomas and leukemias in female rats and testicular tumors in male rats. Chronic exposure to ethanol also produces cancers (e.g., esophageal) in laboratory animals. 

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