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Pharmacology: Cocaine

Good, Bad, & the Ugly
by

Jane Smith

on 6 April 2011

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Transcript of Pharmacology: Cocaine

COCAINE Good Bad Ugly Mechanism of Toxicity video Introduction:
Cocaine goes by a few other names...
Some of our favorites are: Coke, snow, flake, crack, blow, rock, line, snuff, sugar, snort, and stone.

It's made from coca leaves and the effects include: alertness, wakefulness, increased energy and an overall feeling of euphoria. Cocaine may be smoked, inhaled ("snorted"), ingested or injected.

Cocaine is a psychomotor stimulant is an agent that causes excitement & euphoria, relieve fatigue and increase motor activity. Cocaine is a schedule 2 drug, which means that it's approved for medical use by a written prescription from an MD...
sorry NO REFILLS allowed!

Griffiths PD; Perry RH, Crossman AR (Mar 1994). A detailed anatomical analysis of neurotransmitter receptors in the putamen and caudate Cocaine is one of the most effective local anesthetics when used topically. It is used in nasal and eye surgery, and is also a postent vasoconstrictor, which decreases bleeding during surgery.

See.. it's not so bad.


Guyton, Arthur C. and John E. Hall. Textbook of Medical Physiology, Eleventh Edition. Philadelphia, PA: Elsevier Inc., 2006. Print. Cocaine as a therapeutic agent is used for conditions ranging from epilepsy to neurodegenerative disorders such as Parkinson’s disease. It may, however serve to induce neurologic disorders for which the putamen is responsible for abating such as; Alzheimer's, Huntington's, Wilson's, dementia, and schizophrenia to name a few.

Marchand WR, et al. (Jun 2008). "Putamen coactivation during motor task execution". Neuroreport. The toxic dose is highly variable and depends on individual tolerance and route of administration. “Usual” maximum dose for intranasal local anesthesia is 100 – 200 mg/kg. A typical line of cocaine to be snorted contains 20-30 mg/kg and can be used as a dose several times a day. Ingestion of 1 g as a single dose is fatal. Mechanism of Action Cocaine inhibits the reuptake of the monoamines neurotransmitters into presynaptic terminals. This reuptake process is the means by which these neurotransmitters are removed from the extracellular space. Cocaine serves to potentiate neurotransmission of all three monoamines, it is a serotonin–norepinephrine–dopamine reuptake inhibitor.

Guyton, Arthur C. and John E. Hall. Textbook of Medical Physiology, Eleventh Edition. Philadelphia, PA: Elsevier Inc., 2006. Print. It's a psychomotor stiumulant which increases locomotor activity. The primary binding site resides in the caudate putamen, a region composed predonminantly of dopamine terminals. When the dopamine system is activated we are more positive, excited and eager to go after goals or rewards.

Griffiths PD, et al (Mar 1994). "A detailed anatomical analysis of neurotransmitter receptors in the putamen and caudate". Neuroscience Letters 169 (1-2): 68–72. Cocaine increases dopaminergic activity by binding to the dopamine transporter and inhibiting dopamine uptake.

Weiss F, PauIus M, Lorang M, and KooblIncreases G (1992) "Extracellular Dopamine in the Nucleus Accumbens by
Cocaine Are Inversely Related to Basal Levels"
Dept of Neuropharmacology Univ of Ca Routes of Administration ORAL
Rub powder along gum line or onto cigarette filter to numb gums and teeth. Hence, the names “numbies,” “gummers” or “cocoa puffs” Wrap up in paper and swallow (“parachute”) it Sometimes called a “snow bomb” Insufflation
Cocaine powder must be divided into very fine particles
Devices aka “tooters” utlized
Pour onto flat, hard surface (such as mirror, CD case or book)
Divide into “bump,” “line” or “rail”
Insufflate!
Side Effects: One of the first side effects experienced from cocaine is within 15 minutes after injection. The user immediately wants more even though the dopamine levels in the brain are still higher than normal. With continuous injections of cocaine negative feelings are usually mixed with the highs from the initial effects. General side effects of cocaine include the following: it constricts blood vessels, dilates pupils, increases body temperature, increases heart rate, increases blood pressure and causes headaches. It also causes GI complications such as abdominal pain and nausea which causes a decrease in appetite; this is why chronic users are generally malnourished.  Psychologically users may experience paranoia and hallucinations.

Joaquim R; Mataix-Cols D (Nov 2009). Voxel-wise meta-analysis of grey matter. British Journal of Psychiatry 195: 393–402. Almost all cocaine-related deaths are due to sudden death caused by a cardiac arrest or seizure followed by respiratory arrest.
Cocaine users who have cerebrovascular disease can have fatal arrhythmias and overt myocardial ischemia
Intracranial hemorrhage is also seen with these patients.

Hill G, Johnson E, Ogunaike O (2006) Dept of Anesthesiology Univ of Texas, "General anaesthesia for the cocaine abusing
patient. Is it safe?" COCAINE


References...
DeLong MR; Alexander GE, Georgopoulos AP, Crutcher MD, Mitchell SJ, Richardson RT (1984). "Role of basal ganglia in limb movements". Human Neurobiology 2 (4): 235–44.
Alexander GE; Crutcher MD (July 1990). "Preparation for movement: neural representations of intended direction in three motor areas of the monkey". Journal of Neurophysiology 64 (1): 133–50.
Delong MR; Georgopoulos AP, Crutcher MD, Mitchell SJ, Richardson RT, Alexander GE (1984). "Functional organization of the basal ganglia: contributions of single-cell recording studies". Ciba Found Symp. 107: 64–82.
Marchand WR; Lee JN, Thatcher JW, Hsu EW, Rashkin E, Suchy Y, Chelune G, Starr J, Barbera SS (June 11 2008). "Putamen coactivation during motor task execution". Neuroreport. 19 (9): 957–960.
Griffiths PD; Perry RH, Crossman AR (March 14 1994). "A detailed anatomical analysis of neurotransmitter receptors in the putamen and caudate in Parkinson's disease and Alzheimer's disease". Neuroscience Letters 169 (1-2): 68–72.
Crutcher MD; DeLong MR (1984). "Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity". Exp Brain Res. 53 (2): 244–58.  
Turner RS; Desmurget M, Grethe J, Crutcher MD, Grafton ST (December 2003). "Motor subcircuits mediating the control of movement extent and speed". Journal of Neurophysiology 90 (6): 3958–66.
Miyachi S; Hikosaka O, Miyashita K, Kárádi Z, Rand MK (June 1997). "Differential roles of monkey striatum in learning of sequential hand movement". Exp Brain Res. 115 (1): 1–5.  
^ Packard MG; Knowlton BJ (2002). "Learning and memory functions of the Basal Ganglia". Annu Rev Neurosci. 25: 563–93.
Yamada H; Matsumoto N, Kimura M (April 7 2004). "Tonically active neurons in the primate caudate nucleus and putamen differentially encode instructed motivational outcomes of action". Journal of Neuroscience 24 (14): 3500–10.
Ell SW; Marchant NL, Ivry RB (2006). "Focal putamen lesions impair learning in rule-based, but not information-integration categorization tasks". Neuropsychologia 44 (10): 1737–51.
Zeki S; Romaya JP (2008). "Neural Correlates of Hate". PLoS ONE 3 (10): e3556.
DeLong MR; Wichmann T (January 2007). "Circuits and circuit disorders of the basal ganglia". Arch Neurol. 64 (1): 20–4.
de Jong LW; van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, van der Grond J (December 2008). Brain 131 (12): 3277–85.
Martin H. Teicher; Carl M. Anderson, Ann Polcari, Carol A. Glod, Luis C. Maas & Perry F. Renshaw (2000). "Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry". Nature Medicine 131 (12): 470–3.
Radua, Joaquim; Mataix-Cols, David (November 2009). "Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder". British Journal of Psychiatry 195: 393–402. Clinical Manifestations:
Euphoria (due to inhibition of dopamine reuptake)- difficult to distinguish between cocaine and amphetamines

Sympathomimetic Effects:
Mydriasis
Increased Heart Rate
Increased Blood Pressure
(vasoconstriction and renin release)
Bronchodilation Side Effects cont: Side Effects cont: Summary:
Coca leaves native to Andes Mountains. Locals have chewed on leaves for centuries to work better in high altitude air 1855: Cocaine first isolated from coca leaf for use for medicinal purposes. Quickly became popular for energizing and euphoric effects in cocaine-laced tonics, elixirs, and wines, and as a “cure all” ingredient in over-the-counter medications
Sigmund Freud promoted cocaine as a safe and useful tonic that could cure depression and sexual impotence
1886: Added to Coca Cola (later removed in 1903) 1914: Harrison Act outlaws use of cocaine in over-the-counter products
1920: Dangerous Drug Act proclaims cocaine an illegal narcoticBut the drug was still in high demand… 1970s: Cocaine boom
Early 1980s: Crack, a rock-like, rapidly reacting form of cocaine base, hits the market
1984-1990: “Crack epidemic.” Why?
Cheap and affordable
Easy to smoke
Rapid and intense effects
Cocaine and Crack Injection

Provides highest blood levels of drug in shortest amount of timeAE: ringing in the ears known as “bell ringer”
Combination of cocaine + heroin = “speedball”Responsible for numerous celebrity deaths such as John Belushi, River Phoenix, Chris Farley Suppository
Cocaine can be dissolved in water and withdrawn into an oral syringe
This method of administration is also known as “plugging” Inhalation
Smoking freebase or crack cocaine is most often accomplished using a pipe made from a small glass tube Acute Toxicity

Mild Overdose:
Agitation, dizziness, tremor, blurred vision

Severe Overdose:
Hyperpyrexia, convulsions, ventricular dysrhythmias, hemorrhagic stroke; angina pectoris and myocardial infarction may develop due to coronary artery spasm

Psychological symptoms:
Severe anxiety, paranoid ideation, hallucinations (visual, auditory, or tactile)

Chronic Toxicity
Atrophy of the nasal mucosa
Loss of sense of smell
Extreme cases: necrosis and perforation of the nasal septum
Smoking cocaine base: injury to lungs Crack Babies?
Although cocaine readily crosses the placenta, recent reports say that fetal injury is minimal. The report from JAMA states that the data available shows fetal injury from cocaine is considerably less than that from alcohol or tobacco (Lehne, 2008).
Tolerance, Dependence, Withdrawal
It is possible that regular cocaine use may result in increased sensitivity.
No certainty regarding dependence: Some report having little to no withdrawal symptoms after discontinued use.
Others report: Dysphoria Craving Fatigue Depression Prolonged sleep
Full transcript