Crack is WhackThe Psycho-stimulant Cocaine

Biology of Toxins 445 - Toolson

Aaron Rivera, Sheila Rivera, Anabel Guerra

May 4, 2007

C17H21NO4

sweet lady cocaine

Chemical structure

Powder cocaine

Crack cocaine

Manufacture & Distribution

Cocaine comes from the Erythroxylum plant and is manufactured by converting tropinone into 2-carbomethoxytropinone, reducing this to ecgonine, and then converting the ecgonine to cocaine. This isn't as easy as it sounds.

South Texas remains the leading entry area for cocaine smuggled into the United States.

Mexican DTOs have developed Atlanta as a staging area for direct wholesale cocaine distribution to East Coast drug markets

• the US government seized 153,000 lbs (69,000 kg) of cocaine in 2006 but this is estimated to be only 3-5%• A conservative estimation of the amount in circulation in the US during 2006 is more than 3 million lbs (1.4 million kg)

• 1 kg sells for approximately $20,000 in today’s market • the amount seized by the DEA is worth approximately $1.4 billion which means that the amount of cocaine in circulation 2006 was worth roughly $27 billion!!

Cocaine in the US

Drug contamination of US paper currency

Jenkins AJ.Office of the Cuyahoga County Coroner, 11001 Cedar Road, 44106,Cleveland, OH, USA Forensic Sci Int 2001 Oct 1;121(3):189-93

ABSTRACTIt is known that US paper currency in the general circulation is contaminated with cocaine. Several mechanisms have been offered to explain this finding, including contamination due to handling during drug deals and the use of rolled up bills for snorting. Drug is then transferred from one contaminated bill to others during counting in financial institutions. The possibility of contamination of currency with other drugs has not been reported. In this study, the author reports the analysis of 10 randomly collected US$ 1 bills from five cities, for cocaine, heroin, 6-acetylmorphine (6-AM), morphine, codeine, methamphetamine, amphetamine and phencyclidine (PCP). Bills were immersed in acetonitrile for 2h prior to extraction and GC-MS analysis. Results showed that 92% of the bills were positive for cocaine with a mean amount of 28.75+/-139.07&mgr;g per bill, a median of 1.37&mgr;g per bill, and a range of 0.01-922.72&mgr;g per bill. Heroin was detected in seven bills in amounts ranging from 0.03 to 168.50&mgr;g per bill: 6-AM and morphine were detected in three bills; methamphetamine and amphetamine in three and one bills, respectively, and PCP was detected in two bills in amounts of 0.78 and 1.87&mgr;g per bill. Codeine was not detected in any of the US$ 1 bills analyzed. This study demonstrated that although paper currency was most often contaminated with cocaine, other drugs of abuse may be detected in bills.

The take-home thought is: the $1 bills in your wallet have a high probability of cocaine contamination and you might just have other drugs on them too.

Factoids A high from snorting may last 15-30 min while a high from

smoking cocaine may last only 5-10 min, so euphoria is temporary either way

And Keep in Mind… 0.5 kg will land a person 5 yrs in federal prison Cocaine is the no. 2 cause of drug-related emergency room

visits in the US National average of drug overdose is 7.1 deaths/100,000

people; NM is 11/100,000; Rio Arriba County is 33.1/100,000

Routes of Administration

• Injection

• Insufflation (snorting or sniffing)

• Smoking

• Coca leaf infusions

• Chewing/Eating the leaves

The Pope on Coke

His Holiness The Pope enjoyed the invigorating properties of coca wine. Leo XIII carried a personal hipflask to fortify himself in time of need. A grateful Pope awarded a Vatican gold medal to its distinguished originator, the Corsican-born pharmacist and businessman, Angelo Mariani. Mariani had a keen eye for the benefits of celebrity-endorsement.

Drug Testing

Cocaine and benzoylecgonine, a cocaine metabolite, can be detected in urine 2-4 days after the initial use; the initial screening cutoff level is 300ng/ml

Chronic cocaine use can detected in the urine up to 3 weeks or longer depending on the individual

Hair samples can be taken to test for cocaine; typically 1.5 inches, starting at the root, is tested and cocaine use can be revealed up to 90 days after use

Pharmacological Actions

Cocaine Affects

• the Central Nervous System

• the Cardiovascular System

• Skeletal Muscle

• Thermoregulation

• the Sympathetic Nervous System

• Local Actions

• the Eye

CNS Effects The first recognizable CNS action is on the

cerebral cortex Cortical action is manifested as increased

motor activity With small doses motor activity remains

coordinated, but as dosages increase lower motor centers are affected causing tremors and convulsive movements

Action of cocaine on the medulla results in increased respiratory rate

The vasomotor and vomiting centers can be stimulated and emesis is not uncommon

Central stimulation is soon followed by depression of the vital medullary centers which results in death due to respiratory failure

Positron emission tomography scans showing the average level of dopamine receptors in six primates' brains. Red is high- and blue is low-concentration of dopamine receptors. The higher the level of dopamine, the fewer receptors there will be. GVG is a drug typically used to treat epilepsy however, it blocks cocaine’s action in the brains of primates and is being tested as a treatment for cocaine addiction in humans.

Cardiovascular Systems Effects

Cocaine causes vasoconstriction which coupled with tachycardia causes a rapid rise in blood pressure

Large IV doses of cocaine may result in immediate death from cardiac failure due to direct toxic action on the heart muscle

Topical application causes direct vasoconstriction of the regional blood vessels

Effects on Thermoregulation

Cocaine is extremely pyrogenic 3 factors contribute to the rise in body temperature

1) Increased muscular activity augments heat production

2) Vasoconstriction due to central vasomotor stimulation decreases heat elimination

3) Direct action on the heat regulating centers (hypothalamus)

Sympathetic Nervous System & Skeletal Muscle Effects

Cocaine can potentiate the responses of sympathetically innervated organs to epinephrine, norepinephrine and SNS stimulation

Cocaine potentiates excitatory and inhibitory responses of muscles and glands to epinephrine or adrenergic nerve impulses

There is no evidence that cocaine increases the strength of muscular contraction therefore, it must be concluded that the ability of the drug to delay fatigue results from central stimulation which masks the sensation of fatigue

Local Actions

The most important local action of cocaine is its ability to block nerve conduction when brought into direct contact with nerve tissue (feelings of numbness)

Blocks terminal sensory nerve fibers in concentrations as low as 0.02%

Higher concentrations are required to block conduction in nerve trunks or to produce anesthesia by direct contact

Derivatives of cocaine, such as Novocain, are commonly used today for their analgesic properties

Effects on eye

Ophthalmic application results in anesthesia of the cornea, constriction of the conjunctival vessels, and blanched sclera

Anesthesia may also extend to the iris Cocaine has varying effects on

intraocular pressure of the eye, in most cases it is reduced via vasoconstriction

Application to the eye occasionally precipitates an attack of acute glaucoma

Cornea may be come dry and contaminated with foreign material.

Local vasoconstriction limits cocaine’s rate of absorption; despite this fact, the rate of absorption may easily exceed the rate of detoxification and excretion

Cocaine is absorbed through all sites of application including mucus membranes

Orally administered cocaine is hydrolyzed in the gastrointestinal tract and rendered ineffective

After absorption cocaine is detoxified by the liver It is estimated that the liver can detoxify one minimal lethal

dose in 60 minutes Some maybe excreted unchanged in the urine

Absorption and excretion

Addiction and Tolerance

“The cocaine addict is not a normal individual but is often a dangerous and debased person. Many addicts become paranoid and suffer from ideas of persecution, as a result they may carry weapons which they do not hesitate to use. Addicts believe they are being threatened and have their thoughts

read by others.” -Louis S. Goodman, M.A., M.D., & Alfred Gilman, Ph.D, The Pharmacological Basis of Therapeutics, 1955

Auditory, visual and tactual hallucinations are not uncommon The sensation of something alive crawling on the skin is a

common complaint In addition to mental deterioration the cocaine addict may

experience digestive disorders, nausea, loss of appetite, emaciation, sleeplessness, tremors and occasionally convulsions

Continued use of cocaine leads to tolerance

Mechanisms of Addiction & Tolerance Cocaine binds to mesolimbic dopamine uptake transporter

proteins effectively blocking the reabsorption of dopamine Dopamine stays in the synapse and stimulates the postsynaptic

receptor cells over and over again allowing the body to feel its affects over a prolonged period

As reabsoption continues to be blocked, accumulated dopamine in the synapses is washed away and degraded

Eventually the brain’s dopamine supply becomes inadequate to sustain a normal mood; the synaptic bulb cannot exocytose dopamine fast enough to maintain normal levels and pleasure circuits go dry

Mechanisms of Addiction & Tolerance

Meanwhile, postsynaptic cell membranes become hypersensitive and express new dopamine receptors

A viscous cycle is established: cocaine is needed to experience pleasure but using it increases depletion of the neurotransmitter

Dopamine initially gets the brain’s attention causing glutamate to be released in the pleasure center at 50-100% of the normal level

Repeated exposure to cocaine activates glutamate transmission and prompts the synthesis of more glutamate receptors

Glutamate signaling seems to cause more permanent changes in the brain (synaptic potentiation) that lead to compulsive drug seeking behavior

Long-term Effects of Addiction

From snorting- Loss of the sense of smell Nosebleeds Problems with swallowing Hoarseness Chronically runny nose Perforated septumFrom injecting- May suffer severe allergic reactions Infection of the injection site Increased risk of contracting HIV and other blood-borne

diseases

Actress Danniella Westbrook after years of cocaine use

To wrap it up folks just remember:

Blow No Mo’ cuz Crack Is Whack!

Bibliography

Goodman, Louis S. M.A., M.D., & Gilman, Alfred Ph.D (1956). The Pharmacological Basis of Therapeutics (2nd ed.). New York: The MacMillan Company.

Marieb, Elaine N., R.N., Ph.D. (2004). Human Anatomy and Physiology (6th ed.). San Francisco: Pearson Education, Inc.

National Institute on Drug Abuse (NIDA) http://www.nida.nih.gov/ResearchReports/Cocaine/cocaine.htmlhttp://www.drugabuse.gov/scienceofaddiction/

US Drug Enforcement Agency (DEA) http://www.usdoj.gov/dea/concern/18862/cocaine.htm http://www.usdoj.gov/dea/concern/cocaine.html

United Nations Office of Drugs and Crime (UNODC) http://www.unodc.org/unodc/world_drug_report.html

http://images.google.com/imgres?imgurl=http://www.med.umich.edu/opm/newspage/images/vasoconstriction.jpg&imgrefurl=http://www.med.umich.edu/opm/newspage/2003/cocaineheart.htm&h=180&w=240&sz=86&hl=en&start=6&um=1&tbnid=vXOLQrB_lCERbM:&tbnh=83&tbnw=110&prev=/images%3Fq%3Dvasoconstriction%2Bfrom%2Bcocaine%26svnum%3D10%26um%3D1%26hl%3Den%26client%3Dsafari%26rls%3Den%26sa%3DN

http://www.erowid.org/chemicals/cocaine/cocaine_testing.shtml