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Lecture 6

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PSYC 3403
Tarry Ahuja

Lecture 6 Overview Cocaine • Pharmacokinetics • Pharmacological effects Amphetamines • Pharmacological effects • Ice • Methamphetamines Cocaine **DON’T NEED TO KNOW THIS!!** Derived from the Erythroxylon coca plant Native to the mountain ranges of SouthAmerica Locals would chew on the coca leaves Help with endurance, stamina, and appetite 90% of all cocaine consumed from Columbia Plant is resistant to drought and disease Harvested several times per year Field workers were given 4 breaks daily Active ingredient first isolated in 1860 Cocaine is a crystalline tropane alkaloid Cocaine (history) Freud (1884) used and prescribed the drug Believed it to be the “cure-all” Thought it could cure opioid addiction Later learned of its tolerance and dependence called it the “third scourge” of humanity Cocaine (metabolism) **KNOW THIS!!** Cocaine has a half-life of approximately 50 minutes Brain: 8 hours, urine: 12 hours Major metabolite is benzoylecgonine **KNOW THIS!!** • Formed when cocaine is broken down Benzoylecgonine can be detected for 2 weeks **KNOW THIS!!** • Biomarkers (marker for drug testing) • Rather than look for the drug itself in the system, look for the biomarkers instead since they last in the system longer Interacts with EtOH • Cocaine interacts with alcohol and produces a different metabolite than if using cocaine without alcohol Produces metabolite: **KNOW THIS!!** • Cocaethylene (cocaine + alcohol) Blocks presynaptic DAreuptake transporter Still have cocaine in blood and now have cocaethylene “doubled your pleasure” Metabolite more toxic than cocaine Cocaine (administration) Cocaine hydrochloride is the white powder you see in movies Can be administered: • Orally • Intranasal • Intravenous • Smoking (exclusively crack cocaine) To make it, smush leaves and mix with hydrochloric acid to break down cocaine and this makes cocaine hydrochloride when dry • Overall chemical property is that it is acidic Dictates speed and duration of “high” Cocaine HCl is a potent vasoconstrictor • ‘vaso’refers to blood vessels, ‘constrictor’means it is restricting • The cocaine in the blood supply actually limits more getting into your blood because it constricts If snorting cocaine, the molecules stick to the skin/septum and the goal is to dilute in and enter blood supply Oral • Lasts the longest, takes the longest to set in • Peak plasma levels are very low • Least addictive Intranasal = last a little longer Smoking= 8-10 seconds for onset, but duration of high is only 5-10 minutes • Most addictive You don’t want peaks and valleys in drug effects (ups and downs are undesirable) Producing crack cocaine is different than cocaine HCl, crack cocaine is produced with an ether- has higher burning point so you can smoke it, the residual ether in the crack rocks are what make the popping/cracking noise When you smoke crack, hits you much harder than snorting cocaine Effects different structures of the brain, makes it more addictive Crack users will shoot 8-10 rocks a day because the crash happens sooner’someone snorting cocaine might only snort one or two lines a night • Want to prevent withdrawal symptoms Cocaine (administration) Depending on route of administration, how fast it enters the body varies Smoking is faster than snorting • If you snort cocaine, must enter bloodstream, be pumped to your heart, then to your lungs, then back to your heart, and finally to your brain If you smoke cocaine (crack), goes in from your lung supply, to your heart, to your brain • This is why smoking crack is faster than snorting cocaine Some of the limitations of snorting cocaine • Infections: what surface am I using? Dirty money being used to snort it • What is the cocaine being cut with? Drugs are almost always mixed with other substances (ex: baby powder) so the drug dealers can make more money • This also affects the potency- no way to measure how much drug is actually in a line of cocaine; can result in overdose (OD) Cocaine (mechanism) Pharmacological characteristics: **KNOW THESE FOR MIDTERM!!** • Potent local anesthetic  In the past there were gels (similar to Orajel) which contained cocaine to kill pain • Vasoconstrictor • Psychostimulant  This is what makes it a drug of abuse, this is the desired effect Cocaine potentiates synaptic action of: • Dopamine  Helps the synaptic action of dopamine  Anytime you mess with dopamine, risk addiction • Norepineprine • Serotonin DAchanges associated with: • Behavior-reinforcing  If you take cocaine, chances are you will take it again • Psychostimulant properties  Linked to what cocaine does to dopamine system Changes in DAlevels in: • Nucleus accumbens • Dopaminergic reward system  Any time a drug affects DAor the more that drug is repeated the more likely you will become addicted to the drug  Lower level drug (ex: caffeine) will have less of an effect than a higher level drug (ex: heroine/cocaine) Site for euphoric/additive properties • Linked to changes in dopamine On the left (active dopamine transporter) • When signal comes in, dopaminergic neuron (vesicle filled with dopamine) dumps out dopamine into the cleft to interact with postsynaptic dopamine receptors • After some time, the residual that’s left will get broken down by enzymes, and some of it will get taken back into the cell and repackaged by dopamine transporter On the right (blocked dopamine transporter) • Cocaine is going in and blocking the dopamine transporter, so now we have more dopamine in the cleft for longer time so more dopamine is interacting with dopamine receptors longer • Cocaine blocks reuptake of dopamine Cocaine (mechanism) Changes in 5-HT also responsible: • Remove DAtransporter experiments  Born without dopamine transporters and cocaine tested on them- should have no effect (nothing to block) but there was one, because also affects ser
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