COCAINE
by dr. Italiano Claudio, a former physician Ser.T.
Origin and history of cocaine: It 's an alkaloid
removable leaves Eritroxylon Coke. Isolated for the first time in 1880 as an
anesthetic for operations on the eye, used later in the interventions on the
nose, throat and teeth having vasoconstrictor properties and thus reducing
bleeding. It is generally used as cocaine hydrochloride. The free-base form is
inhaled or snorted, while the use ev is less frequent. Used in the U.S. by 20-30
million people daily by 800,000, is known from time immemorial: Inca skulls in
which cocaine was found is also 150 hours in human tissues;
Incas believed that chewing coca leaves the soul could be transferred from one
body to another and we put between the teeth of dead leaves. Freud introduced
the culture of cocaine in Europe, using it as an antidepressant, but cocaine was
also used as medicine for diarrhea, syphilis, etc.. The writer Stevenson, who
probably used it, wrote Dr. Jackill and Mr. Hyde, Joyce wrote the Ulysses
instead, where on some pages of the book, the effect of drugs are disconnected
periods without syntax or grammar ... In the U.S. in 1886 was contained up to
60mg / glass in the cola drink! In 1914, however, after heavy intoxication was
eliminated and there are currently only XCola drink preparations of the extracts
of coca leaves but no cocaine. In the 60s there was another boom er is passed to
the "crack", so called for crackles that are heard while smoking pipes in the
form of solid crystals of cocaine mixed with sodium hydroxide or NaOH, sometimes
with NaHCO3, sodium bicarbonate, or ammonia and water to assorbimentoo fast.
Chemistry is a benzoilmetilecgonina the ecgonine is a basic amino alcohol
similar to atropine, the amino alcohol dell'atropina. The cocaine is then an
ester of benzoic acid containing a nitrogenous base.
Preparation: large quantities of leaves, 5 cm to 1% of cocaine, are thrown in
barrels or in holes in the ground to rubble, mixed with kerosene or other
solvents to make a kind of fleshy pulp that is treated with hydrochloric acid
for remove impurities and other unnecessary chemicals. When the process is
finished you have the cocaine hydrochloride in the form of crystalline powder,
odorless and white reaching a purity level of up to 90-100% and another solvent
used is benzene but cause leukemia and cancer in cocaine!
Absorption: you can also smoke coca paste, the tox make use of pure cocaine
hydrochloride inhaling, "sniffing" in pulling the strips powder straws in each
nostril at doses of 20-50 mg. The purity of street cocaine varies between 10%
and 50% being used adulterants cutting: lactose, mannitol, procaine, lidocaine,
glucose, caffeine, talc, quinine and morphine itself. The half-life is 40-45
minutes (half life = half life time of substances in the blood), the
bioavailability is low, absorption is slow, a cocaine rush, a kind of orgasm
that involves the whole body, so the tox hires inhalation or intravenously,
orally clearly not the aim of having a flash of intense pleasure, the same
vision of snow in New York is recalling stimulus in the mind of the idea of
cocaine cocainoma (Associative Memory - phenomenon neuronal plasticity), heated
in cocaine crystals are obtained by extraction in sodium hydroxide or sodium
hydroxide, known as "rock", if the characteristic noise damage smoked crack, a
mixture of ammonia and water solution of cocaine hydrochloride, in free solution
pulmonary bed large quantities of cocaine, with significant increase in peak
blood you smoke pipes in the form of crystals with concentrations ranging from
20 to 30% in the brain up to 20 times greater than the blood, doses ranging from
20 mg to 50 mg for the crack up to 250 mg!
Phenomenon of addiction: Cocaine is addictive type that manifests psychological
inability to experience pleasure (dell'anedonìa concept), there is a reason why
cocaine evokes the production of dopamine in the pleasure centers of perception
(ventromedial nucleus of the midbrain) which is the least noble of the brain but
certainly important for the conservation of the pleasure centers are located
where sex and power. Of substance abuse is causing drug - seeking behavior, ie,
the act obsessive-complulsivo Search Drugs as the ventromedial nucleus of the
midbrain there are projections in the motor centers and, therefore, a motor
associative memory: an animal that is Moving back to the substance, after he
learned how to get the pleasure, the drug substance is characterized as positive
reinforcement.
Meso-cortico-limbic system: there is a nervous system in our brain that makes us
a) feel the pleasure and 2) back to the motor with a message like: eg classic
baby hears the mother's breast and go back to the breast. Cocaine, in this sense,
is the most powerful drug to stimulate this system in addition to its
recruitment determines euphoria and well-being, but is also associated with an
unpleasant action ansiogenetica and dysphoria. The tox understand that cocaine
was not sufficient and that test anxiety and dysphoria for this reason and then
pull back to cocaine in order to win the dysphoria. 3), awareness of the
increased performance of physical and sexual certainly not least the first time
that it takes, returning to the resolution of the withdrawal syndrome. The
depressed patients, anhedonia, if they take cocaine and feel like become,
therefore, easy to cocaine.
This system is activated if you took cocaine and takes pleasure because dopamine
is released, but messages are activated motors that you return with pleasure.
How can this be?
It was shown that cocaine blocks the reuptake of synaptic dopamine in the range
that since dopamine is responsible for neurotransmission at postsynaptic
pleasure and so the site is inhibited system reuptake transporter (reuptake)
whose job is to modulate synaptic concentration of dopamine in the range.
Cocaine, in fact, interacts with the system operator, responsible for DA
reuptake and blocks but it can also be done with Noraepinefrina or NE (norepinephrine)
and 5HT (read five hydroxytryptamine or serotonin) but has higher affinity (ie
capacity to bind) with the dopamine reuptake site, but if it blocks the reuptake
of NE action prevails peripheral vasoconstriction mediated by norepinephrine
precisely with the possibility of death from myocardial infarction and coronary
spasm, with block serotonin reuptake will have a stimulation of pyramidal cells
of the cerebral cortex that those delegated to the transformation of sensations
into perceptions, their activation gives me eg. vision but a real and concrete
hyperstimulation (eg under influence of ecstasy) I will feel strange kind of
LSD, with an increase of the sphere and therefore perceptual illusions and
hallucinations, paranoid schizophrenia, to stimulation with increasing DA, I
have pleasure intense.
Pharmacological mechanism: The receptors on which fixed the DA are 5 types, in
turn divided into subgroups, we regard the action of cocaine involving those D1
and D2, because after stimulation of the ventral mesencephalic tegmentum there
are two nerve projections to the nucleus accumbens (message motor) to D1
receptors that cause damage and increase dell'AMPciclico dysphoric effect, that
is the sadness of cocaine and irritable with reduction dell'AMPciclico D2 (second
messenger), so after stimulus with cocaine during the first 10 minutes we
euphoria with the release of dopamine D2, then anxiety and dysphoria to dopamine
D1 receptor stimulation, the cocaine addict who believe that euphoric effects
have gone back to summarize and cocaine, for which an individual it will crack
the binge of cocaine and will go into depression (CRASH), the phenomenon of
tolerance exists for cocaine for which the tox will need to increase the doses,
even a gram / day, but it draws more and more is dysphoria; D2 receptors are
indeed coupled to an inhibitory G protein and the transduction of the message
after interaction with the DA will be an action of reducing levels of cyclic AMP
second messenger or by inhibiting meaning. Stimulation of D1, however, because
the cause dysphoria and increases cAMP formed dynorphin, and DA Case D1 receptor
stimulation and produce dynorphin, another receptor that acts on kappa and
determines dysphoria. Prohibiting cocaine, therefore, the pleasure mediated by
D2 receptor and hence the euphoria fades but remains only the dysphoria and
anxiety and the object becomes anhedonia (ie no pleasure), depressed and lost.
Then appears the craving, the need to return to obsessive and compulsive drug
use.
Effect: dysphoria
Effect: pleasure and then decline
Effects of abuse: So we have 3 stages of doping: 1) phase is characterized by
craving the stimulation of D1 as the nucleus accumbens through dynorphin
produces dysphoria and the subject returns obsessively and compulsively cocaine
hoping to achieve the reduction of dysphoria, 2) and then the phase of the
crash, after 9 hours and 4 days after repeated cocaine intake is passed to the
phase of the crash, because you run out of DA, and appears hard, easy
exhaustibility respect to fatigue, 3 ) phase in which the subject goes to sleep
and when you will awaken the hunger but not the craving, but after the crash
there was a period of abstinence and the subject will become anhedonia and after
1 / 10 weeks anhedonia and craving ferocious if the person exceeds 10 weeks in
phase 3 and has a resolution of mood away from cocaine and provided it snows,
otherwise the subject will relapse (relapse) and return to the abuse of cocaine;
Psychiatric aspects and Soma: The subject cocaine may develop delusions of
grandeur, reference and themes of persecution, the subject is afraid and smokes
crack and plan to use substances that he knows have a sedative effect: alcohol
and heroin and speed makes -ball or fastball, that is, heroin + cocaine together,
but here goes towards double intoxication.
Cocaine can develop a paranoid schizophrenic and that is a danger to avoid,
which means there are illusions microzoopsie, that is the subject sees small
animals, bugs cocaine, perhaps due to vasoconstriction and cut the meat with a
sharp object, there vasoconstriction and myocardial infarction, stroke with
hypertension, cardiac arrhythmias and constriction of blood vessels with
perforation of the nasal septum and reduced seizure threshold with risk of
seizures, appears on sexual impotence and hyperprolactinemia and gynecomastia.
Problems in pregnancy: the USA 6 to 45% of newborns are exposed to cocaine,
crack's babies, exposed to passive smoking but also after conception cocaine
attaches to sperm and remains in the zygote causes vasoconstriction: the
resulting low metabolic exchanges between mother and fetus, fetal hypoxia,
placental detachment as possible, fetal hypoglycemia, fetal low birth weight,
microcephaly, disorders of myelination, and risk to the child who will be very
irritable, with seizures and at risk of sudden death from cerebral subarachnoid
hemorrhage: school age will be misfit, has an attention deficit and
hyperactivity syndrome. Today's crack babies are treated with Prozac, fluoxetine
hydrochloride.
Therapy
Objectives: 1) block the action of cocaine -> mission impossible, because the
present state of our knowledge there is no drug cocaine antagonist;
2) enhance the adverse effects, such as Antabuse for ethanol;
3) try to solve the psychological dependence from 1 to 10 weeks after the crash,
and solve the anhedonia;
you can do with an antidepressant based DESIMIPRAMINA at doses between 10 and 75
mg / day in 3 doses, 25 mg NORTIMIL CPR, because it reduces the craving
dopaminimimetico;
Bromocriptine, Parlodel, which increases L dopa, as in Parkinson's disease, but
may cause an increase in psychological dependence, because the pharmacological
effect of giving an increased release of dopamine modeled essentially those of
cocaine!
4) Use of partial agonists, more or less power but reduced total effect, ie
drugs that may now have agonist action, ie giving the effect of dopamine, when
we are at the stage of anhedonia, with increased mood and, conversely, of almost
antagonistic when the subject takes cocaine, the modulating effect of the
substance through the pharmacological action, they are PRECLAMOLO, SDZ208911 the
TERGURIDE, SDZ 208,912.
5) Antibodies directed against the molecule that cocaine or benzoilecgonica,
detach from the benzoic acid molecule, as with those against digoxin in the
intoxication by digitalis;
6) The treatment of psychological support that may be useful.
.......
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