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42 Cards in this Set
- Front
- Back
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What are the 3 sympathomimetic stimulants?
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-Cocaine
-Amphetamines -Methylphenidate |
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How do the sympathomimetic stimulants act in general?
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By enhancing catecholaminergic neurotransmission
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What type of compound is cocaine and where is it found naturally?
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-Psychoactive Alkaloid
-Found in the coca plant |
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What is the chemical nature of Cocaine and in what form is it best absorbed?
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-Weak base
-Unionized and best absorbed in the NONprotonated B form at alkaline pH |
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How did native peoples use cocaine to increase CNS stimulation?
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By chewing it with lime juice to raise the pH of their mouths so that when they felt wired enough, they could just spit the leaves out to stop absorption.
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What are the 2 forms in which Cocaine is used in the US?
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-Hydrochloride salt
-Free base |
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What is Cocaine hydrochloride soluble in?
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Water
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What is the free base Cocaine form soluble in?
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Lipids/ether/organic solvent
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How is the free base form of Cocaine made?
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By putting the Hydrochloride Cocaine salt in water with an alkaline pH to push the BH+ into B + H+; then add organic solvent, shake, and the B will be left in the organic solvent
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Why would you want to go to all the trouble of extracting the free B form from a hydrochloride salt of cocaine?
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Because it is MUCH more volatile and much more rapidly absorbed into across nasal passages and alveoli when smoked.
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So how is Cocaine absorbed?
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Through any mucous membrane - mouth, nasal passages, or lungs.
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What is the main determinant of the time it takes for Cocaine to reach its peak effect, and its duration of action?
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The route of administration
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What routes of administration will result in the shortest time to peak effect of cocaine?
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IV or smoking
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Where are the enzymes for metabolizing Cocaine located in the body?
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-Plasma
-Liver |
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What is the plasma half life of Cocaine? CNS halflife?
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Plasma = 50 min
CNS = 10-30 min |
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So what do you have to do to maintain the euphoria from Cocaine?
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Use over and over again
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What do urine screens for Cocaine use detect?
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Cocaine METABOLITES in the urine
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What is the general mechanism of action of Cocaine?
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POTENT INHIBITOR via binding to the REUPTAKE transporter for
-norepinephrine -dopamine -serotonin |
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What are the reuptake carriers responsible for normally?
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Degradation and removal of the neurotransmitters from the synapse
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What is the main thing that the reinforcing effects of euphoria/pleasure seen with Cocaine use due to?
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Increased DOPAMINE in the synapses in ascending mesolimbic pathways
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What does the loss of Dopamine Neg feedback inhibition in the presynaptic terminal lead to?
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Increased activity of Tyrosine and Tryptophan hydroxylases
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How do free NE/Dopamine normally cause feedback inhibition of Tyrosine/Tryptophn hydroxylases?
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By binding THB cofactor and inhibiting it from being able to act as a cofactor to the enzymes
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So what are the two main mechanisms of Cocaine actions and what is the end result?
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-Blocks presynaptic NT reuptake
-Increases enzymatic synthesis and release End result: lots of receptor activation |
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What is the one possible clinical use of cocaine?
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Its action as a Local Anesthetic in areas that need little-low bleeding via VASOCONSTRICTION (ie the nose)
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So what are the 3 general pharmacological effects of cocaine?
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-Peripheral sympathomimetic
-Increased alertness/vigilance -Euphoria/elation/competency |
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What are the 2 peripheral sympathomimetic effects of cocaine, and what are they due to?
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-Vasoconstriction
-Tachycardia Due to inhibition of NE reuptake IN THE PERIPHERY |
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What are the increased alertness and vigilance effects of Cocaine due to?
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Inhibition of NE reuptake IN CNS SYNAPSES - used by the chilean natives for these mild effects
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What are the effects that cocaine addicts are going for?
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Elation/Euphoria and feelings of well-being and competency
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What are the feelings of Elation/Euphoria due to?
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Inhibition of DOPAMINE reuptake in the MESOLIMBIC CIRCUIT
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What are the euphoric effects of Cocaine responsible for?
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Its very high abuse liability
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What is the tolerance and physical dependence that occurs with heavy cocaine use like in general?
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Mild
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Why is withdrawal syndrome worse when you d/c Depressants than Stimulants?
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Because chronic use of depressants upregulates pathways that will result in seizures when overstimulated by removing the CNS depressant drugs.
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How would CNS stimulants like cocaine cause seizures?
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When OVERDOSE occurs
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What are 2 toxic effects that can occur from cocaine overdose?
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-Seizures
-CV effects - MI/arrythmia |
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What is a major toxic effect of longterm cocaine use?
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Neurotoxic damage to Dopaminergic neurons
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What causes more significant effects on the developing fetus; alcohol (FAS) or cocaine?
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Cocaine
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What are 4 effects that cocaine can have on the developing fetus?
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-Premature labor
-Low birthweight -Learning/emotional problems -Attachment disorder |
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Though cocaine doesn't really cause much physical dependence or withdrawal syndrome, what DOES it produce?
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PROFOUND PSYCHOLOGICAL DEPENDENCE
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What does the psychological dependence upon cocaine result in?
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-Drug craving
-Drug seeking 10 minutes after the last dose |
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When is the abuse liability of cocaine highest?
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With dosage forms that deliver drug rapidly to CNS - Smoking/IV
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What are 4 symptoms of cocaine withrawal? How are they treated?
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-Dysphoria
-Depression -Sleepiness -Fatigue Not usually treated |
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What is basically the only therapeutic use of Cocaine?
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Local anesthetic in nasal surgery when bloodflow needs to be kept to a minimum (vasoconstricting effects)
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