Alcohol Abuse

The World Health Organization’s (WHO) definition of drug dependence is ‘a state, psychic and sometimes physical, resulting from the interaction between a living organism and a drug characterized by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects and sometimes to avoid the discomfort of its absence’. More recent definitions include the WHO’s ICD-10 and the American Psychiatric Association’s DSM-IV diagnostic criteria for Substance-Related Disorders, which emphasize the importance of loss of control over drug use and its consequences in limiting other, non-drug-related activities, in addition to tolerance and physical dependence. In the above definitions, a distinction is made between physical and psychological dependence. Although psychological dependence has not been shown to produce gross structural changes, it must be assumed that changes have occurred in the brain at a molecular or receptor level. Central to the definition of psychological dependence is the compulsion or craving to take a drug repeatedly. In contrast, physical dependence occurs in the absence of a drug, when a range of symptoms – a withdrawal state – is present. The ease and degree to which withdrawal symptoms develop defines the liability of a particular drug to produce physical dependence. As a generalization, the withdrawal syndrome seen after cessation of a drug tends to be the opposite of the symptoms produced by acute administration of that drug (e.g. anxiety, insomnia and arousal seen after withdrawal of alcohol or benzodiazepines, or depression and lethargy seen after withdrawal of stimulants). Physical and psychological dependence may be distinguished clinically. For instance, abrupt cessation of tricyclic antidepressants leads to sympathetic nervous system activation, without psychological dependence, whereas nicotine withdrawal produces predominantly psychological changes, with minimal physical symptoms. The major difference between drug abuse and drug dependence is quantitative.

Tolerance, when repeated exposure to a drug produces progressively diminished effects, is another important concept. It may be caused by changes in the rate at which the drug is distributed or metabolized in the body, or by adaptive processes occurring in the brain. A distinct feature is cross tolerance, where tolerance to one type of drug is associated with tolerance to other drugs. Cross-tolerance, which can encompass chemically distinct drugs, has been clearly demonstrated for alcohol, benzodiazepines and other sedative drugs. It forms the basis for substitution treatment of dependency.

PATHOPHYSIOLOGY OF DRUG DEPENDENCE

Most people who are exposed to drugs do not become dependent on them. Factors that increase the likelihood of addiction include: • Genetic factors: Genetic factors can predispose to dependency, but can also protect against alcoholism (e.g. defective aldehyde dehydrogenase genes – common in East Asians – produce unpleasant flushing/headache after drinking alcohol). • Personality/environment: Drinking or drug-taking behaviour is influenced by the example set by family or peer group, or by cultural norms.

Drug availability and economic factors: Rates of dependence are increased if a drug is easily available. This may explain why dependence on nicotine and alcohol is a much greater public health problem than dependence on illegal drugs, because of their greater availability. Drug use is sensitive to price (e.g. rates of alcoholism are reduced by increasing alcohol prices). • Biochemical reinforcement: Drugs of abuse and dependence have a common biochemical pathway: they all increase dopamine in the nucleus accumbens, associated with mood elevation and euphoria. Behaviourally, this is linked with reinforcement of drug taking. Dependence-potential of different drugs is related to potency in releasing dopamine (cocaine is most potent). The rate of dopamine release is also important, e.g. smoked and intravenous drugs give a more rapid effect than oral drugs.

GENERAL PRINCIPLES OF TREATING ADDICTIONS

By the time an addict presents for assessment and treatment, he or she is likely to have diverse and major problems. There may be physical or mental illness, and emotional or attitudinal problems, which may have contributed to the addiction and/or resulted from it. Their financial and living circumstances may have been adversely affected by their drug habit and they may have legal problems relating to drug possession, intoxication (e.g. drink–driving offences), or criminal activities carried out to finance drug purchases. Attitudes to drug use may be unrealistic (e.g. denial). The best chance of a successful outcome requires that all of these factors are considered, and the use of a wide range of treatment options is likely to be more successful than a narrow repertoire. Treatment objectives vary depending on the drug. Complete abstinence is emphasized for nicotine, alcohol or cocaine addiction, whereas for heroin addiction many patients benefit from methadone maintenance. Other objectives are to improve the health and social functioning of addicted patients. Treatment success can only be determined over a long time, based on reduction in drug use and improvements in health and social functioning. A treatment programme should include medical and psychiatric assessment and psychological and social support. Addicts should be referred to specialist services if these are available. Other services based in the voluntary sector (e.g. Alcoholics Anonymous) are also valuable and complementary resources. Medical and psychiatric assessment may need to be repeated once the patient is abstinent, as it is often difficult to diagnose accurately certain disorders in the presence of withdrawal symptoms (e.g. anxiety, depression and hypertension are features of alcohol withdrawal, but are also common in abstinent alcoholics).

ALCOHOL

Ethyl alcohol (alcohol) has few clinical uses when given systemically, but is of great medical importance because of its pathological and psychological effects when used as a beverage. Alcohol is the most important drug of dependence, and in Western Europe and North America the incidence of alcoholism is about 5% among the adult population.

Pharmacokinetics Ethyl alcohol is absorbed from the buccal, oesophageal, gastric and intestinal mucosae – approximately 80% is absorbed from the small intestine. Alcohol delays gastric emptying and in high doses delays its own absorption. Following oral administration, alcohol can usually be detected in the blood within five minutes. Peak concentrations occur between 30 minutes and two hours. Fats and carbohydrates delay absorption. Alcohol is distributed throughout the body water. About 95% is metabolized (mainly in the liver) and the remainder is excreted unchanged in the breath, urine and sweat. Hepatic oxidation to acetaldehyde is catalysed by three parallel processes. The major pathway (Figure 53.1) is rate limited by cytoplasmic alcohol dehydrogenase using nicotinamide adenine dinucleotide (NAD) as coenzyme. Alcohol elimination follows Michaelis–Menten kinetics, with saturation occurring in the concentration range encountered during social drinking. A small additional ‘dose’ can thus have a disproportionate effect on the concentration of alcohol in the plasma.

Effects of alcohol Nervous system: Alcohol decreases concentration, judgement, discrimination, and reasoning and increases self-confidence. Progressively increasing plasma concentrations are associated with sensations of relaxation followed by mild euphoria, in coordination, ataxia and loss of consciousness. At high blood concentrations, the gag reflex is impaired, vomiting may occur and death may result from aspiration of gastric contents. The importance of alcohol as a factor in road traffic accidents is well known (see Figure 53.2). The central depressant actions of alcohol greatly enhance the effects of other central depressant drugs. In patients with organic brain damage, alcohol may induce unusual aggression and destructiveness, known as pathological intoxication. Death may also result from direct respiratory depression. Chronic neurological accompaniments of persistent alcohol abuse include various forms of central and peripheral neuro degeneration, most commonly involving the vermis of the cerebellum, and a peripheral neuropathy. Nutritional deficiencies may contribute to the pathogensesis of neurodegeneration. Wernicke’s encephalopathy (difficulty in concentrating, confusion, coma, nystagmus and ophthalmoplegia) and Korsakov’s psychosis (gross memory defects with confabulation and disorientation in space and time) are mainly due to the nutritional deficiency of thiamine associated with alcoholism. Any evidence of Wernicke’s encephalopathy should be immediately treated with intravenous thiamine followed by oral thiamine for several months. Psychiatric disorder is common and devastating, with social and family breakdown.

Circulatory: Cutaneous vasodilatation causes the familiar drunkard’s flush. Atrial fibrillation ( embolization) is important. Chronic abuse is an important cause of cardiomyopathy. Withdrawal (see below) causes acute hypertension and heavy intermittent alcohol consumption can cause variable hypertension by this mechanism which can exacerbate or be mistaken for essential hypertension Gastrointestinal: Gastritis, peptic ulceration, haematemesis (including the Mallory–Weiss syndrome, which is haematemesis due to oesophageal tearing during forceful vomiting, as well as from peptic ulcer or varices). Liver pathology includes fatty infiltration, alcoholic hepatitis and cirrhosis. Alcohol can cause pancreatitis (acute, subacute and chronic).

Metabolic: Alcohol suppresses ADH secretion and this is one of the reasons why polyuria occurs following its ingestion. Reduced gluconeogenesis leading to hypoglycaemia may cause fits. The accumulation of lactate and/or keto acids produces metabolic acidosis. Hyperuricaemia occurs (particularly, it is said, in beer drinkers) and can cause acute gout.

Haematological effects: Bone marrow suppression occurs. Folate deficiency with macrocytosis is common and chronic GI blood loss causes iron deficiency. Sideroblastic anaemia is less common but can occur. Mild thrombocytopenia is common and can exacerbate haemorrhage. Neutrophil dysfunction is common even when the neutrophil count is normal, predisposing to bacterial infections (e.g. pneumococcal pneumonia), which are more frequent and serious in alcoholics.

In pregnancy: Infants of alcoholic mothers may exhibit features of intra-uterine growth retardation and mental deficiency, sometimes associated with motor deficits and failure to thrive. There are characteristic facial features which include microcephaly, micrognathia and a short upturned nose. This so-called fetal alcohol syndrome is unlike that reported in severely undernourished women. Some obstetricians now recommend total abstinence during pregnancy.

Medical uses of alcohol Alcohol is used topically as an antiseptic. Systemic alcohol is used in poisoning by methanol or ethylene glycol, since it competes with these for oxidation by alcohol dehydrogenase, slowing the production of toxic metabolites (e.g. formaldehyde, oxalic acid).

Management of alcohol withdrawal syndrome develops when alcohol consumption is stopped or severely reduced after prolonged heavy alcohol intake. Several features of acute withdrawal are due to autonomic over activity, including hypertension, sweating, tachycardia, tremor, anxiety, agitation, mydriasis, anorexia and insomnia. These are most severe 12–48 hours after stopping drinking, and they then subside over one to two weeks. Some patients have seizures (‘rum fits’ generally 12–48 hours post abstinence). A third set of symptoms consists of alcohol withdrawal delirium or ‘delirium tremens’ (acute disorientation, severe autonomic hyperactivity, and hallucinations – which are usually visual). Delirium tremens often follows after withdrawal seizures and is a medical emergency. If untreated, death may occur as a result of respiratory or cardiovascular collapse. Management includes thiamine and other vitamin replacement, and a long-acting oral benzodiazepines (e.g. chlordiazepoxide or diazepam), given by mouth if possible. The initial dose requirement is determined empirically and is followed by a regimen of step-wise dose reduction over the next two to three days. The patient should be nursed in a quiet environment with careful attention to fluid and electrolyte balance. Benzodiazepines (intravenous if necessary, are usually effective in terminating prolonged withdrawal seizures – if they are ineffective the diagnosis should be reconsidered (e.g. is there evidence of intracranial haemorrhage or infection). Psychiatric assessment and social support are indicated once the withdrawal syndrome has receded.

Long-term management of the alcoholic Psychological and social management: Some form of psychological and social management is important to help the patient to remain abstinent. Whatever approach is used, the focus has to be on abstinence from alcohol. Avery small minority of patients may be able to take up controlled drinking subsequently, but it is impossible to identify this group prospectively, and this should not be a goal of treatment. Voluntary agencies such as Alcoholics Anonymous are useful resources and patients should be encouraged to attend them. Alcohol-sensitizing drugs: These produce an unpleasant reaction when taken with alcohol. The only drug of this type used to treat alcoholics is disulfiram, which inhibits aldehyde dehydrogenase, leading to acetaldehyde accumulation if alcohol is taken, causing flushing, sweating, nausea, headache, tachycardia and hypotension. Cardiac dysrhythmias may occur if large amounts of alcohol are consumed. The small amounts of alcohol included in many medicines may be sufficient to produce a reaction and it is advisable for the patient to carry a card warning of the danger of alcohol administration. Disulfiram also inhibits phenytoin metabolism and can lead to phenytoin intoxication. Unfortunately, there is only weak evidence that disulfiram has any benefit in the treatment of alcoholism. Its use should be limited to highly selected individuals in specialist clinics. Acamprosate: The structure of acamprosate resembles that of GABA and glutamate. It appears to reduce the effects of excitatory amino acids and, combined with counselling, it may help to maintain abstinence after alcohol withdrawal.