Biomedical Engineering Reference
In-Depth Information
4.1.1
Pharmacodynamics
Cocaine acts as a potent local anesthetic and is a strong CNS stimulant: it extends
and intensifies the effects of dopamine, norepinephrine, serotonin neurotransmitters
[
3
]. The effects of cocaine can vary in relation to the individual characteristics, the
administered dose, frequency of use, and route of administration. The intranasal
administration causes plasma peak concentrations after 5-20 min, the euphoric
effect in 15-20 min with a half-life of 40 min. The oral route involves a slow and
low absorption with plasma peak concentrations after approximately 90 min and
euphoric effect in 15-20 min. Intravenous plasma peak is immediate, euphoric
effect occurs after 4-8 min with a half-life of about 40 min. Finally it may be admin-
istered through inhalation of combustion products or crack vapors, with great
absorption speed.
4.1.2
Effects
A few seconds after the administration there is a subjective euphoric phase (rush), a
feeling of extreme pleasure and comfort. Then a rapid rebound of the cortical
depression (down) leads the subject to a condition of anxiety, depression, and irrita-
bility. When regularly used, the physical and psychological discomfort that accom-
panies the end of the effects is configured as a real abstinence syndrome (crash),
whose main symptoms are depression, physical breakdown, irritability, and above
all the compulsive and uncontrollable desire for cocaine.
The clinical symptoms of cocaine intake are the following: vasoconstriction,
dilated and reactive pupils, hyperthermia, arrhythmias, increased blood pressure,
dry mouth, increased sweating, tremors, dizziness, muscle spasms, hyperactivity,
and insomnia. Cocaine-related deaths are generally caused by cardiac arrest or sei-
zures followed by respiratory arrest [
11
] .
4.1.3
Pharmacokinetics
Cocaine easily passes the blood brain barrier and the plasma levels are detectable
for about 4-6 h after nasal ingestion; it is rapidly metabolized into inactive metabo-
lites: benzoylecgonine (BEG), ecgonine methyl ester (EME), and ecgonine [
12
] .
These molecules are biomarkers for the identification of cocaine abuse due to their
higher biological half-life with respect to cocaine (about fivefold).
EME and BEG, which is mainly obtained by enzymatic hydrolysis, represents
respectively the 32-49 % and 29-45 % of total urinary metabolites; cocaine can be
converted, in small amounts, to norcocaine (NCOC) and psychoactive metabolite
norbenzoylecgonine (NBE). The combined intake of alcohol and cocaine deter-
mines the formation of a pharmacologically active metabolite, the cocaethylene
(ethyl ester of benzoylecgonine, CE), with a significant liver toxicity [
13
] .
