DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

mucosa, producing higher cocaine levels in the blood and a more
rapid onset of stimulation. Subsequently, it was found that a solution
of cocaine hydrochloride could be administered intravenously,
giving a more rapid onset of stimulatory effects. Each newly available
cocaine preparation that provided greater speed of onset and an
increment in blood level was paralleled by a greater likelihood of
addiction. In the 1980s, the availability of cocaine to the American
public was increased further with the invention of crack cocaine.
Crack, sold illegally and at a low price ($1-3 per dose), is alkaloidal
cocaine (free base), which can be readily vaporized by heating.
Simply inhaling the vapors produces blood levels comparable to
those resulting from intravenous cocaine owing to the large surface
area for absorption into the pulmonary circulation following inhalation.
The cocaine-containing blood then enters the left side of the
heart and reaches the cerebral circulation without dilution by the systemic
circulation. Thus, inhalation of crack cocaine is much more
addictive than chewing, drinking, or sniffing cocaine. Inhalation,
with rapid attainment of effective drug levels in the brain, also is the
preferred route for users of nicotine and cannabis.
Although the drug variables are important, they
do not fully explain the development of addiction. Most
people who experiment with drugs of high addictive
potential (addiction liability) do not intensify their drug
use and lose control. The risk for developing addiction
among those who try nicotine is about twice that for
those who try cocaine (Table 24–2). This does not
imply that the pharmacological addiction liability of
Table 24–2
Dependence among Users 1990–1992
EVER
RISK OF
USED ∗ ADDICTION ADDICTION
AGENT % % %
Tobacco 75.6 24.1 31.9
Alcohol 91.5 14.1 15.4
Illicit drugs 51.0 7.5 14.7
Cannabis 46.3 4.2 9.1
Cocaine 16.2 2.7 16.7
Stimulants 15.3 1.7 11.2
Anxiolytics 12.7 1.2 9.2
Analgesics 9.7 0.7 7.5
Psychedelics 10.6 0.5 4.9
Heroin 1.5 0.4 23.1
Inhalants 6.8 0.3 3.7
*The ever-used and addiction percentages are those of the general
population. The risk of addiction is specific to the drug indicated and
refers to the percentage who met criteria for addiction among those
who reported having used the agent at least once (i.e., each value in
column 4 was obtained by expressing the number in column 3 as a
percentage of the number in column 2, subject to errors of rounding).
Source: Anthony et al., 1994.
nicotine is twice that of cocaine. Rather, there are other
variables listed in the categories of host factors and
environmental conditions that influence the development
of addiction.
Host (User) Variables. In general, effects of drugs vary
among individuals. Even blood levels can show wide variation
when the same dose of a drug on a milligram-perkilogram
basis is given to different people. Polymorphism
of genes that encode enzymes involved in absorption,
metabolism, and excretion and in receptor-mediated
responses may contribute to the different degrees of reinforcement
or euphoria observed among individuals
(Chapters 6 and 7).
Children of alcoholics show an increased likelihood of developing
alcoholism, even when adopted at birth and raised by nonalcoholic
parents. The studies of genetic influences in this disorder
show only an increased risk for developing alcoholism, not a 100%
determinism, consistent with a polygenic disorder that has multiple
determinants. Even identical twins, who share the same genetic
endowment, do not have 100% concordance when one twin is alcoholic.
However, the concordance rate for identical twins is much
higher than that for fraternal twins. The abuse of alcohol and other
drugs tends to have some familial characteristics, suggesting that
common mechanisms may be involved.
Innate tolerance to alcohol as measured by level of response
to alcohol administered under experimental conditions may represent
a biological trait that contributes to the development of alcoholism
(Chapter 23). While innate tolerance increases vulnerability to alcoholism,
impaired metabolism may protect against it. See Chapter 23
for a discussion of the genetic variation common in Asian populations
that results in facial flushing and reduced alcohol intake or no
alcohol intake in those homozygous for the gene variant. Similarly,
individuals who inherit a gene associated with slow nicotine metabolism
may experience unpleasant effects when beginning to smoke
and reportedly have a lower probability of becoming nicotine
dependent.
Psychiatric disorders constitute another category of host variables.
Drugs may produce immediate, subjective effects that relieve
preexisting symptoms. People with anxiety, depression, insomnia,
or even subtle symptoms such as shyness may find, on experimentation
or by accident, that certain drugs give them relief. However,
the apparent beneficial effects are transient, and repeated use of the
drug may lead to tolerance and eventually compulsive, uncontrolled
drug use. While psychiatric symptoms are seen commonly in drug
abusers presenting for treatment, most of these symptoms begin after
the person starts abusing drugs. Thus, drugs of abuse appear to produce
more psychiatric symptoms than they relieve.
Environmental Variables. Initiating and continuing illegal
drug use appear to be influenced significantly by
societal norms and peer pressure. Taking drugs may be
seen initially as a form of rebellion against authority. In
some communities, drug users and drug dealers are
role models who seem to be successful and respected;
thus, young people emulate them. There also may be a
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CHAPTER 24
DRUG ADDICTION