Adverse Consequences of Alcohol Abuse and Dependence

Adverse Consequences of Alcohol Abuse and Dependence
W. Alexander Morton, Pharm.D., BCPP
Professor of Pharmacy Practice
Associate Professor of
Psychiatry and Behavioral Sciences
Medical University of South Carolina;
Institute of Psychiatry, Charleston, SC

Sophie Robert, Pharm.D.
Psychiatric Pharmacy Practice Resident
Medical University of South Carolina,
Charleston, SC

Alcohol, also known as ethanol and ethyl alcohol, is an interesting drug for a numberof reasons. Although most consumers do not consider alcohol to be a drug, alcohol in fact may be the most thoroughly studied of all drugs. The scientific literature contains numerous documented effects of alcohol.1 However, many healthcare practitioners fail to appreciate the clinical picture produced by alcohol in patients with undiagnosed conditions who use or abuse alcohol. When presented with a case involving early physical symptoms of alcohol abuse, primary care physicians in one study failed to diagnose the problem 94% of the time.2 In addition to its other adverse events, alcohol is thought to be responsible for up to 105,000 deaths per year, not including deaths attributed to drunken driving.1

This article is intended to help health practitioners recognize some of the physical and mental complications of alcohol abuse and dependence in patients with undiagnosed illnesses. The information provided can help practitioners formulate treatment plans for patients who use alcohol and who have concomitant medical and psychiatric illnesses. In addition, it may be used to educate patients, helping them view alcohol differently when they have difficulty recognizing their alcohol use as a problem.


Popular Myths About Alcohol Use

People consuming excessive amounts of alcohol will use several popular myths to justify their continued drinking. These myths are discussed below:

Alcohol is good for your heart. Overall, excess alcohol is bad for the heart because the heart has to work harder and it may function irregularly.

Alcohol protects against heart attacks. This is only partly true. Alcohol decreases the "bad" cholesterol (LDL) and increases the "good" cholesterol (HDL). When used in small amounts, alcohol has been associated with less coronary heart disease. This fact is often cited by alcoholics in an attempt to justify their continued use. The main problem with this rationalization is that alcoholics do not drink small amounts.

Alcohol relaxes you. Alcohol does act to relax a person as the blood alcohol level rises. However, alcohol levels above modest limits can actually make one more anxious as alcohol is eliminated from the body.

Alcohol helps you sleep. Alcohol does help people fall asleep; however, middle-of-the-night awakening is common, as well as inability to fall back asleep. Adverse effects on sleep have been documented to last for months after alcohol has been stopped.

Suggested Reading:
* Rosenqvist M. Alcohol and cardiac arrhythmias. Alcohol Clin Exp Res 1998;22(7,suppl.):318S-322S.
* Koskinen P, Kupari M, et al. Alcohol and new onset atrial fibrillation: a case-control study of a current series. Br Heart J 1987;57(5):468-473.
* Thun MJ, Peto R, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med 1997;337(24): 1705-1714.
* Camargo CA, Hennekens CH, et al. Prospective study of moderate alcohol consumption and mortality in US male physicians. Arch Intern Med 1997;157(1):79-85.
* Roth T, Roehrs T, et al. Pharmacological effects of sedative-hypnotics, narcotic analgesics, and alcohol during sleep. Med Clin N Am 1985; 69(6):1281-1288.

Effects of Alcohol
The unique properties of alcohol have been linked to its effects on the cell membrane.3 In general, the cell membrane regulates the activity and stability of the cell. Alcohol nonspecifically increases cell membrane permeability. In addition, it affects various neurotransmitters and their receptors, such as gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), and serotonin.3 Thus, for any cell within the body, alcohol can exert an effect--including possible adverse events. This ability alone is enough to consider alcohol a universal cellular toxin. However, the toxic effects of alcohol frequently are not seen until after many years of use.

Absorption and Distribution: Alcohol is quickly and almost completely absorbed in the stomach.4 Food and juice slow the absorption, thus, the effects.5 Most people like alcohol because it works quickly (within 5 to 15 minutes). There is a connection between choice of abused substances and the rate at which the drug produces desirable effects: the faster the onset of action, the higher the abuse potential.6

Alcohol is distributed throughout all fluids and tissues of the body, in proportion to their water content;7 this is one reason why it causes so many problems and systemic complications. Women usually have more fat tissue than men, and will generally achieve higher blood alcohol concentration when given the same dose of alcohol per kg of total body weight.7

Pharmacology: Alcohol is a central nervous system depressant.8 While some excitatory transmitter systems are enhanced by acute alcohol ingestion, most of them are inhibited. The inhibitory transmitter systems are augmented, resulting in disinhibition. Because of this decrease in inhibition, people's behavior may change dramatically. As a result of its interaction with various neurotransmitters and receptors, alcohol produces changes in the channels of the cell membrane to allow influx and efflux of ions, such as chloride, calcium, sodium, and potassium.8 This change in ion flux leads to changes in cellular polarization which, for the most part, results in inhibition of neurotransmission.

Metabolism: Alcohol is eliminated predominantly by breakdown in the liver. It is primarily metabolized by alcohol dehydrogenase to acetaldehyde, which is then rapidly destroyed by aldehyde dehydrogenase.9 On average, the body metabolizes 1 oz (30 mL) of alcohol in about 3 hours, although this metabolism rate is weight-dependent.10 Genetically controlled variants of these enzymes in ethnic groups such as the Asian population are associated with a lower risk of alcoholism.11 This fact has led to the hypothesis that higher acetaldehyde levels produce an uncomfortable sensation that can deter excessive use. A small amount of alcohol--usually less than 1%--is eliminated unchanged through the lungs. This contributes to the odor of alcohol on one's breath.4

Approved Uses
There are numerous industrial uses for alcohol, including as a germicide and a solvent; however, medical indications and approved uses are limited.10 The only FDA-approved indication is in combination with dextrose as an intravenous solution for increasing caloric intake and replenishing fluids.12 Alcohol has an unapproved use in the treatment and slowing of premature labor.12 It has also been used to treat methanol poisoning10 and as a pain reliever when injected into a nerve to cause neural toxicity.10

Adverse Effects
Alcohol can produce a variety of adverse effects at different stages of use (FIGURE 1)10,13,14 Stages of use include acute ingestion of moderate amounts, severe intoxication, chronic ingestion, withdrawal, and effects as a result of malnutrition. Mental and psychiatric adverse events include anxiety, panic, sedation, euphoria, irritability, restlessness, aggressiveness, violence, depression, sleep disturbances, memory and cognitive deficits, confabulation, hallucinations, and delusions. A lifetime comorbidity of alcohol and psychiatric disorders of 86% has been reported, and often there is a worsening of psychiatric diagnoses.15,16

CNS effects can include headaches, cerebral atrophy, ataxia, and seizures. Skull fractures and subdural hematoma can occur. The eyes may undergo blurred vision, loss of vision, or color vision abnormalities. Cardiovascular effects can include cardiomyopathy, congestive heart failure, arrhythmias, coronary artery disease (with heavy consumption), hypertension, edema, increased risk of stroke with heavy drinking (especially hemorrhagic), but possible reduced risk of ischemic stroke with moderate doses. Respiratory effects can range from increased risk of pneumonia to asthma or acute respiratory distress.

GI effects include gastritis, ulcers, bleeding, malabsorption of food and nutrients such as vitamins, diarrhea or constipation, and esophageal varices. Liver problems include fatty liver, hepatitis, jaundice, fibrosis, cirrhosis, blood coagulopathies, hypoprotenemia, and ascites. Pancreatitis can develop. Genitourinary disorders such as electrolyte imbalances, urinary tract infections, and sexual dysfunction may occur. Neurological complications include paresthesias, peripheral neuropathies, extrapyramidal symptoms and pain as well as fetal alcohol syndrome. Musculoskeletal problems such as myalgias, cramps, atrophy, weakness, joint inflammation, worsening of rheumatoid arthritis, gout, bone ischemia, necrosis, and hypofunctioning marrow can arise.

Hematological disorders are common and include iron deficiency anemia, macrocytic anemia, leukopenia, and thrombocytopenia. Dermatological adverse effects can include dermatitis, flushing, angiomas, urticaria, bruising, and sweating. Endocrine complications include altered glucose tolerance, unstable diabetes, menstrual cycle irregularities, and gynecomastia. In addition, the immune system has an impaired response. Finally, alcohol use has been associated with neoplasms in the upper digestive and respiratory tracts, liver, and with possible increases in breast and large bowel cancers.


Drug Interactions
Alcohol can alter the elimination of certain drugs by affecting gastric emptying, hence their absorption, or liver metabolism.17 Binge drinking is associated with inhibition of cytochrome P4502E1 (CYP2E1), whereas chronic heavy alcohol intake induces the activity of that enzyme group. Induction of CYP2E1 can lead to production of metabolites more toxic than the parent compound, such as is seen with concomitant use of acetaminophen.17 Alcohol can also enhance the adverse effects of various drugs, especially the sedative effects of benzodiazepines and older antihistamines.17

Use of alcohol in combination with cocaine can produce cocaethylene. This metabolite has a higher toxicity than either agent alone and has been found to produce marked toxicity.18 Recently, the combination of alcohol and methylphenidate has been found to undergo the same transformation, and may be the cause of serious adverse events.19




Long-Term Use
People who use alcohol regularly over several months can become physically dependent on it. Upon abruptly stopping, withdrawal will start within 4 to 12 hours. The symptoms will vary considerably from person to person. Sometimes the person will be asymptomatic. Withdrawal can last from 3 to 10 days. If severe withdrawal occurs and goes untreated, death can result.20

Many alcohol-dependent people never go into withdrawal because they are always drinking small amounts. Morning drinking may be an attempt to treat withdrawal. Very few people drink in the morning to get intoxicated or drunk; instead they drink to maintain performance at work. Tolerance to alcohol occurs quickly, so that more is needed to produce the same effect.21 People who can "hold their liquor" have most likely developed tolerance.8,22

Alcohol Dependence
Chemical dependence on alcohol affects almost every aspect of a person's life. In addition to the physical and mental effects cited, a person with alcohol problems will usually have major problems at work or school, with his or her family, or with friends. Financial and legal problems are also usually present. For a diagnosis of alcohol dependence, a person need only have three of the following:23

-Tolerance to the effects of alcohol so that a person needs more to produce the wanted effect--or gets less effect with the same amount.

-Withdrawal such that characteristic symptoms occur when the person stops drinking--or the person drinks to relieve withdrawal symptoms.

-Alcohol is consumed in larger amounts--or for a longer time than was intended.

-A person makes repeated attempts to cut down or control the amount of alcohol consumed.

-A lot of time is spent in obtaining alcohol or recovering from its effects (hangover).

-Important social or recreational activities are given up because of alcohol use.

-A person continues to drink even though he or she knows his or her medical or psychiatric problem is made worse by drinking.

Acute Toxicity
Acute ingestion of large amounts of alcohol can result in death due to cardiovascular collapse and respiratory arrest. Blood levels associated with coma and death average 400 mg/dL;10 however, this varies considerably; some individuals have tolerated levels as high as 1,510 mg/dL.24 (Hangover is the aftereffects of consuming alcohol and is usually related to amount consumed. It may be a combination of mild withdrawal and side effects, both mental and physical.)25

Despite the common belief that beer, wine, and liquor have different pharmacological effects, these effects depend only on the percentage of alcohol contained in the beverage. Certain substances in various beverages have been reported to produce more hangover effects. Some beverages also can be consumed faster than others, but the active ingredient is still ethyl alcohol.

Treatment
Alcohol dependence is straightforward, but difficult to treat. Withdrawal is usually treated with a safer, cross-tolerant drug; benzodiazepines are the agents of choice.26 Treatment is given for only 3-7 days to reduce the associated 10% death rate closer to 0%-1%.20 Concomitant medical and psychiatric problems, which are frequent, need to be addressed and treated effectively.20 Education about the disease of alcoholism is essential. Supportive treatment in the form of psychotherapy and group therapy is often initiated.20 Family therapy is almost always indicated, as there is often serious dysfunction in an alcoholic's family. Most people are encouraged to attend Alcoholics Anonymous (AA), as this is one consistent modality that helps people recover.20

Comorbid psychiatric disorders need aggressive treatment, usually with pharmacologic and nonpharmacologic treatment. Referral to practitioners with experience in addiction treatment may be useful in developing a successful treatment plan to prevent or minimize relapse. Recovering addicts may require initial and/or long-term treatment with nonaddictive medications. Pharmacological treatment of ethanol dependence with agents, e.g., naltrexone, can reduce drinking frequency and relapse rate.27 All substances with potential for abuse should be stopped and avoided.28 Learning and practicing alternative, safe activities that produce pleasure and decrease stress is essential in treatment and recovery.20

Conclusion
Alcohol is a drug. Practitioners need to be reminded that excessive use and/or high doses of alcohol can have profound effects on almost every system in the human body. Many medical and psychiatric conditions are often exacerbated, making these conditions difficult to control. FIGURES 1 and 2 help to demonstrate potential adverse effects of alcohol and may help practitioners rethink a patient's treatment plan if alcohol is involved and the patient is not responding optimally.

posted by Robert Heard at 9:27 AM