A Textbook of Clinical Pharmacology and Therapeutics

● Introduction 433
● Pathophysiology of drug dependence 433
● General principles of treating addictions 434
● Opioid/narcotic analgesics 434
CHAPTER 53
DRUGS AND ALCOHOL ABUSE
INTRODUCTION
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.
● Drugs that alter perception 437
● Central stimulants 438
● Central depressants 439
● Miscellaneous 442
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 crosstolerance,
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.
Key points
Features of drug dependence
• A subjective awareness or compulsion to use a drug,
often related to unsuccessful efforts to reduce drug
intake.
• Continued drug use despite awareness of its harmful
effects on physical health, social functioning, etc.
• Priority of drug-taking or obtaining drugs over other
activities, limiting normal social or work roles.
• The development of tolerance and withdrawal
symptoms.
• After abstinence, dependence may recur rapidly with
reuse of the drug.
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.