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

654 Withdrawal signs and symptoms occur when drug
administration in a physically dependent person is terminated
abruptly. Withdrawal symptoms have at least
two origins:
SECTION II
NEUROPHARMACOLOGY
• Removal of the drug of dependence
• CNS hyper-arousal owing to readaptation to the
absence of the drug of dependence
Pharmacokinetic variables are of considerable
importance in the amplitude and duration of the withdrawal
syndrome. Withdrawal symptoms are characteristic
for a given category of drugs and tend to be
opposite to the original effects produced by the drug
before tolerance developed. Thus, abrupt termination of
a drug (such as an opioid agonist) that produces miotic
(constricted) pupils and slow heart rate will produce a
withdrawal syndrome including dilated pupils and
tachycardia. Tolerance, physical dependence, and withdrawal
are all biological phenomena. They are the natural
consequences of drug use and can be produced in
experimental animals and in any human being who takes
certain medications repeatedly. These symptoms in
themselves do not imply that the individual is involved
in misuse or addictive behavior. This form of dependence
should not be confused with addiction (compulsive
drug-taking). Patients who take medicine for appropriate
medical indications and in correct dosages still may
show tolerance, physical dependence, and withdrawal
symptoms if the drug is stopped abruptly rather than
gradually. For example, a hypertensive patient receiving
a β adrenergic receptor blocker such as metoprolol
may have a good therapeutic response, but if the drug is
stopped abruptly, the patient may experience a withdrawal
syndrome consisting of rebound increased blood
pressure temporarily higher than that prior to beginning
the medication. This response is thought to be due to
adaptive synthesis of β receptors that, in sudden the
absence of antagonist, facilitate an excessive β adrenergic
response in cardiac cells.
Medical addict is a term used to describe a patient in treatment
for a medical disorder who has become “addicted” to the available
prescribed drugs; the patient begins taking them in excessive doses, out
of control. An example would be a patient with chronic pain, anxiety,
or insomnia who begins using the prescribed medication more often
than directed by the physician. If the physician restricts the prescriptions,
the patient may begin seeing several doctors without the knowledge
of the primary physician. Such patients also may visit emergency
rooms for the purpose of obtaining additional medication. This scenario
is very uncommon, considering the large number of patients who
receive medications capable of producing tolerance and physical
dependence. Fear of producing such medical addicts results in needless
suffering among patients with pain, because physicians needlessly
limit appropriate medications. Tolerance and physical dependence
are inevitable consequences of chronic treatment with opioids and
certain other drugs, but tolerance and physical dependence by themselves
do not imply “addiction.”
CLINICAL ISSUES
The treatment of physical dependence will be discussed
with reference to the specific drug of abuse and dependence
problems characteristic to each category: CNS
depressants, including alcohol and other sedatives;
nicotine and tobacco; opioids; psychostimulants, such
as amphetamine and cocaine; cannabinoids; psychedelic
drugs; and inhalants (volatile solvents, nitrous
oxide, and ethyl ether). Abuse of combinations of drugs
across these categories is common. Alcohol is so widely
available that it is combined with practically all other
categories. Some combinations reportedly are taken
because of their interactive effects. An example is the
combination of heroin and cocaine (“speedball”), which
will be described with the opioid category. Alcohol and
cocaine is another very common combination. When
confronted with a patient exhibiting signs of overdose
or withdrawal, the physician must be aware of these
possible combinations because each drug may require
specific treatment.
CNS Depressants
Ethanol. Experimentation with ethanol is almost universal,
and a high proportion of users find the experience
pleasant. More than 90% of American adults report experience
with ethanol (commonly called “alcohol”), and
~70% report some level of current use. The lifetime
prevalence of alcohol use disorders (alcoholism) in men
is almost 20% and in women is 10-15% (Hasin et al.,
2007). This drug is discussed more fully in Chapter 23.
Ethanol is classified as a depressant because it indeed produces
sedation and sleep. However, the initial effects of
alcohol, particularly at lower doses, often are perceived as
stimulation owing to a suppression of inhibitory systems.
Those who perceive only sedation from alcohol generally
choose not to drink when evaluated in a test procedure
(de Wit et al., 1989).
Alcohol impairs recent memory and, in high doses, produces
the phenomenon of “blackouts”: the drinker has no memory of his or
her behavior while intoxicated. The effects of alcohol on memory are
unclear, but evidence suggests that reports from patients about their
reasons for drinking and their behavior during a binge are not reliable.
Alcohol-dependent persons often say that they drink to relieve anxiety
or depression. When allowed to drink under observation, however,
alcoholics typically become more dysphoric as drinking continues