Cocaine & Cocaine & AmphetaminesAmphetamines
Cocaine – Background InfoCocaine – Background Info
From the leaves of Erythroxylan cocaFrom the leaves of Erythroxylan cocaAncient use in S. AmericaAncient use in S. America
Religious, Social, Euphoriant, and MedicinalReligious, Social, Euphoriant, and MedicinalActive alkaloid 1Active alkaloid 1stst purified from the leaves purified from the leaves
in 1860 – What we commonly know as in 1860 – What we commonly know as Cocaine.Cocaine.
Early YearsEarly Years
Proven to be one of the 1Proven to be one of the 1stst local local anesthetics for surgeryanesthetics for surgery
Sigmund Freud obtained and studied Sigmund Freud obtained and studied cocaine’s psychological effectscocaine’s psychological effectsAdvocated its use and prescribed cocaine for Advocated its use and prescribed cocaine for
depression and chronic fatigue.depression and chronic fatigue.Later he realized its adverse side effectsLater he realized its adverse side effects
Early Years Cont.Early Years Cont.
Cocaine incorporated into numerous Cocaine incorporated into numerous medicines and beveragesmedicines and beveragesCoca-ColaCoca-Cola
Harrison Narcotic Act banned its use in Harrison Narcotic Act banned its use in 19141914
Recreational use increased dramatically in Recreational use increased dramatically in the late 1960’sthe late 1960’s
Inexpensive “crack” cocaine use spread in Inexpensive “crack” cocaine use spread in the late 1970’sthe late 1970’s
StatisticsStatistics
In 1985 – Estimated 5.7 million usersIn 1985 – Estimated 5.7 million users In 1997 – Estimated 1.5 million usersIn 1997 – Estimated 1.5 million usersUse in high schools increasingUse in high schools increasing
Forms of CocaineForms of Cocaine
E. coca contains about 0.5-1.0% cocaineE. coca contains about 0.5-1.0% cocaineLeaves are soaked in kerosene and Leaves are soaked in kerosene and
gasoline and mashedgasoline and mashedCocaine extracted in the form of coca Cocaine extracted in the form of coca
pastepastePaste approx 50-60% purityPaste approx 50-60% purity
Cocaine HydrochlorideCocaine Hydrochloride
Paste is treated with numerous chemicals Paste is treated with numerous chemicals to oxidize and purify the paste to form the to oxidize and purify the paste to form the water soluble cocaine hydrochloride water soluble cocaine hydrochloride powder.powder.
Can be close to 100% pureCan be close to 100% pureCan be injected, inhaled as powder, or Can be injected, inhaled as powder, or
ingested orallyingested orallyCannot be smokedCannot be smoked
Freebase FormFreebase Form
A.k.a. Crack CocaineA.k.a. Crack CocaineSimilar to the unpurified insoluble coca Similar to the unpurified insoluble coca
paste.paste.Made by reversing the oxidation processMade by reversing the oxidation processCannot be inhaled (as powder) or injected Cannot be inhaled (as powder) or injected
because it is not water solublebecause it is not water solubleForms a stable vapor when heated and Forms a stable vapor when heated and
inhaled (smoked)inhaled (smoked)
PharmacokineticsPharmacokinetics
Absorption (Cocaine HCl)Absorption (Cocaine HCl)Absorbed from all sites of applicationAbsorbed from all sites of application
Mucous membranes, lungs, stomachMucous membranes, lungs, stomach
VasoconstrictorVasoconstrictorcrosses mucosal membrane poorlycrosses mucosal membrane poorly
Plasma levels peak 30-60 minutesPlasma levels peak 30-60 minutesNasal Inhalation causes slow absorption Nasal Inhalation causes slow absorption
which allows for prolonged euphoric effectwhich allows for prolonged euphoric effect
PharmacokineticsPharmacokinetics
IV injectionIV injectionBypasses all barriers to absorptionBypasses all barriers to absorptionTotal dosage goes into blood stream and Total dosage goes into blood stream and
eventually the braineventually the brainSmoking Cocaine BaseSmoking Cocaine Base
Absorption is rapid and complete at the lungsAbsorption is rapid and complete at the lungsEffects onset in seconds, peaks in 5 minutes Effects onset in seconds, peaks in 5 minutes
and lasts about 30 minutesand lasts about 30 minutes
PharmacokineticsPharmacokinetics
DistributionDistributionPenetrates brain rapidlyPenetrates brain rapidlyBrain concentrations far exceed plasma levelsBrain concentrations far exceed plasma levelsFreely crosses the placental barrierFreely crosses the placental barrier
PharmacokineticsPharmacokinetics
Metabolism & ExcretionMetabolism & ExcretionHalf-life 30-90 min.Half-life 30-90 min.Metabolized by enzymes in both plasma and Metabolized by enzymes in both plasma and
liverliverSlowly removed from brainSlowly removed from brainPositive urine tests for 12 hoursPositive urine tests for 12 hoursMajor metabolite is benzoylecognineMajor metabolite is benzoylecognine
Use With AlcoholUse With Alcohol
In the presence of ethanol a different In the presence of ethanol a different metabolite is produced – cocaethylenemetabolite is produced – cocaethylene
Cocaethylene has the same physiological Cocaethylene has the same physiological effect on the brain as cocaine but more toxiceffect on the brain as cocaine but more toxic Euphoric effects last longer Euphoric effects last longer Increases risk of dual dependencyIncreases risk of dual dependency Increases severity of withdrawalIncreases severity of withdrawal
Alcohol/Cocaine is the largest two drug Alcohol/Cocaine is the largest two drug combination resulting in deathcombination resulting in death
Mechanism of ActionMechanism of Action
Dopaminergic ActionsDopaminergic ActionsPotentiates the synaptic actions of dopamine, Potentiates the synaptic actions of dopamine,
norepinephrine and serotoninnorepinephrine and serotoninCocaine attaches to and blocks presynaptic Cocaine attaches to and blocks presynaptic
dopamine reuptake transport proteinsdopamine reuptake transport proteinsDopamine stays in the synapse longerDopamine stays in the synapse longer
Mechanism of ActionMechanism of Action
Behavior-reinforcing propertiesBehavior-reinforcing propertiesDopamine is the key NT for reinforcementDopamine is the key NT for reinforcementStudies show cocaine increases sensitivity of Studies show cocaine increases sensitivity of
D3 dopamine receptors in nucleus D3 dopamine receptors in nucleus accumbens and other parts of the mesolimbic accumbens and other parts of the mesolimbic system important for behavior reinforcment.system important for behavior reinforcment.Increased density of D3 receptors in OD victimsIncreased density of D3 receptors in OD victimsResponsible for cravingResponsible for craving
Effects of Short Term UseEffects of Short Term Use
Low dose, nontoxic physiological Low dose, nontoxic physiological responses includeresponses include Increased alertnessIncreased alertnessMotor hyperactivityMotor hyperactivityTachycardiaTachycardiaPupillary dilationPupillary dilation Increased glucose availabilityIncreased glucose availabilityShifts of blood flow from internal organs to Shifts of blood flow from internal organs to
musclesmuscles
Effects of Short Term UseEffects of Short Term Use
Psychological Effects Psychological Effects Immediate euporiaImmediate euporiaGiddinessGiddinessEnhanced self-consciousnessEnhanced self-consciousnessForceful boastfulnessForceful boastfulness
These last approx 30 min.These last approx 30 min.
Effects of Short Term UseEffects of Short Term Use
Moderate euphoria lasts for 60-90 minModerate euphoria lasts for 60-90 minA state of anxiety lasts for hoursA state of anxiety lasts for hoursThoughts race, rapid speechThoughts race, rapid speechSleep delayed Sleep delayed Appetite suppressedAppetite suppressedA depressive state followsA depressive state follows
Effects of Short Term UseEffects of Short Term Use
Effects in the CNSEffects in the CNSDepletion of OxygenDepletion of OxygenCerebral AtrophyCerebral AtrophySeizuresSeizuresOthersOthers
Numerous cardiovascular complications Numerous cardiovascular complications can occur with prolonged or single usecan occur with prolonged or single use
Toxic and Psychotic Effects of Toxic and Psychotic Effects of Long-Term, High Dose UseLong-Term, High Dose Use
Anxiety and sleep deprivation increaseAnxiety and sleep deprivation increaseHypervigilanceHypervigilanceSuspiciousness, paranoia, and Suspiciousness, paranoia, and
persecutory fears persecutory fears Toxic Paranoid PsychosisToxic Paranoid Psychosis
Altered perception of reality that can result in Altered perception of reality that can result in aggressive or homicidal actions as a aggressive or homicidal actions as a response to imagined persecutionresponse to imagined persecution
Medical ComplicationsMedical Complications
Many cardiovascular effectsMany cardiovascular effectsHeart attacksHeart attacks Irregular heart rhythmIrregular heart rhythm
Respiratory failureRespiratory failureSeizures Seizures
Tolerance and SensitizationTolerance and Sensitization
Tolerance to the “high” often occurs due to Tolerance to the “high” often occurs due to downregulationdownregulation
Sensitization of the anesthetic and Sensitization of the anesthetic and convulsant effects occursconvulsant effects occursExplains some deaths occurring after low Explains some deaths occurring after low
dosesdoses
ComorbidityComorbidity
Chronic cocaine use produces virtually Chronic cocaine use produces virtually every psychiatric syndromeevery psychiatric syndrome
300 abusers300 abusers56% met current criteria56% met current criteria73% met lifetime criteria73% met lifetime criteria
Alcoholism and Heroin addiction extremely Alcoholism and Heroin addiction extremely high in cocaine usershigh in cocaine users
Cocaine and PregnancyCocaine and Pregnancy
Many indirect effects from the Many indirect effects from the vasoconstriction of mothers blood vesselsvasoconstriction of mothers blood vesselsDecreased blood flow and oxygen to UterusDecreased blood flow and oxygen to UterusAssociated withAssociated with
Placental detachmentPlacental detachmentPreterm laborPreterm laborStillbirthStillbirthLow birth weightLow birth weightOthersOthers
Cocaine and PregnancyCocaine and Pregnancy
Direct effects from cocaine in the fetusDirect effects from cocaine in the fetusNeonatal neurological syndromeNeonatal neurological syndrome
Abnormal sleep patterns, tremors, seizuresAbnormal sleep patterns, tremors, seizures
Increased incidence of SIDSIncreased incidence of SIDSCocaine impaired children show difficulty Cocaine impaired children show difficulty
developing attachments, dealing with developing attachments, dealing with multiple stimuli, aggressionmultiple stimuli, aggression
High incidence of ADHDHigh incidence of ADHD
TreatmentTreatment
There is no consensus on a generally There is no consensus on a generally accepted successful pharmacological accepted successful pharmacological treatment.treatment.
Three problems that complicate therapyThree problems that complicate therapy1.1. Intensity of the drug effect and reinforcing Intensity of the drug effect and reinforcing
actionaction
2.2. Pronounced tendency toward relapsePronounced tendency toward relapse
3.3. Most addicts have a coexisting disorderMost addicts have a coexisting disorder
TreatmentTreatment
Three areas of need for pharmacologic Three areas of need for pharmacologic interventionintervention
1.1. Antiwithdrawal agents to restore the Antiwithdrawal agents to restore the dopaminergic tone of the limbic systemdopaminergic tone of the limbic system
2.2. Anticraving agents that block limbic Anticraving agents that block limbic dopaminergic receptorsdopaminergic receptors
3.3. Treatment of coexisting disordersTreatment of coexisting disorders
TreatmentTreatment
Psychosocial treatment offers the most Psychosocial treatment offers the most promisepromiseCocaine Anonymous Cocaine Anonymous Individual/Group counselingIndividual/Group counselingCognitive behavioral therapyCognitive behavioral therapyPsychodynamic therapyPsychodynamic therapyBehavior Reinforcement strategiesBehavior Reinforcement strategies
Amphetamines - BackgroundAmphetamines - Background
Used for over 60 years therapeutically for Used for over 60 years therapeutically for numerous disordersnumerous disordersSchizophrenia Schizophrenia Addictions (morphine and nicotine)Addictions (morphine and nicotine)Head InjuryHead InjuryHypotensionHypotensionSevere hiccupsSevere hiccupsOthersOthers
Amphetamines - BackgroundAmphetamines - Background
Used in WW II to fight fatigue and Used in WW II to fight fatigue and enhance performanceenhance performance
Widespread abuse began in 1940’s with Widespread abuse began in 1940’s with students and truck drivers to stay awake students and truck drivers to stay awake and increase alertnessand increase alertness
Were used as appetite suppressantsWere used as appetite suppressants
Mechanism of ActionMechanism of Action
All CNS effects caused by the release of All CNS effects caused by the release of newly synthesized NE and dopamine from newly synthesized NE and dopamine from presynaptic storage sitespresynaptic storage sites
Behavioral stimulation and increased Behavioral stimulation and increased motor activity result from stimulation of motor activity result from stimulation of dopamine receptors in the mesolimbic dopamine receptors in the mesolimbic systemsystem
Pharmacological EffectsPharmacological Effects
Physiological EffectsPhysiological Effects Increased BPIncreased BPDecreased HRDecreased HR Increased alertnessIncreased alertnessPsychomotor stimulantPsychomotor stimulantLoss of appetiteLoss of appetite
Pharmacological EffectsPharmacological Effects
Psychological EffectsPsychological EffectsEuphoriaEuphoriaExcitementExcitementMood elevationMood elevation Increased motor/speech activityIncreased motor/speech activityFeeling of powerFeeling of power
Pharmacological EffectsPharmacological Effects
More effectsMore effectsTask performance may improveTask performance may improveDexterity deterioratesDexterity deteriorates
Pharmacological EffectsPharmacological Effects
Metabolized in the liverMetabolized in the liverExcreted through the urineExcreted through the urineDetectable for up to 48 hoursDetectable for up to 48 hours
Pharmacological EffectsPharmacological Effects
At moderate dosesAt moderate dosesRespiratory stimulationRespiratory stimulationSlight tremorsSlight tremorsRestlessnessRestlessnessGreater increase in motor activityGreater increase in motor activity InsomniaInsomniaAgitationAgitation
Pharmacological EffectsPharmacological Effects
At high dosesAt high dosesRepetitive purposeless actsRepetitive purposeless actsSudden outbursts of aggression/violenceSudden outbursts of aggression/violenceParanoid delusionsParanoid delusionsSevere anorexiaSevere anorexiaOverall psychosis and abnormal mental Overall psychosis and abnormal mental
conditionsconditionsAmphetamine Psychosis: paranoid ideationAmphetamine Psychosis: paranoid ideation
Primarily with meth usersPrimarily with meth users
Pharmacological EffectsPharmacological Effects
In addition to the direct effects of the In addition to the direct effects of the drug….drug…. Infections from neglected health careInfections from neglected health carePoor eating habitsPoor eating habitsUse of unsterile equipmentUse of unsterile equipmentGreat deterioration in social, personal, Great deterioration in social, personal,
occupational affairsoccupational affairs
Pharmacological EffectsPharmacological Effects
Long Term evidence shows...Long Term evidence shows...Psychometric deficitsPsychometric deficitsPoor academic performancePoor academic performanceBehavioral problemsBehavioral problemsCognitive slowingCognitive slowingGeneral maladjustmentGeneral maladjustment
The effects on this list are permanent.The effects on this list are permanent.
Dependence and ToleranceDependence and Tolerance
Use becomes compulsiveUse becomes compulsiveDrug strongly effects areas of brain Drug strongly effects areas of brain
associated with behavior reinforcementassociated with behavior reinforcementPhysical dependence follows a classical Physical dependence follows a classical
conditioning modelconditioning modelWithdrawal occurs but not as dramatic as Withdrawal occurs but not as dramatic as
with narcotics and barbiturateswith narcotics and barbituratesSymptoms opposite of drugs effectsSymptoms opposite of drugs effects
Dependence and ToleranceDependence and Tolerance
Tolerance develops rapidlyTolerance develops rapidlyNecessitates the need for markedly higher Necessitates the need for markedly higher
dosesdosesTolerance to the euphoriant effects Tolerance to the euphoriant effects
develops which causes prolonged bingingdevelops which causes prolonged binging
ICEICE
Freebase form of methamphetamineFreebase form of methamphetamineExtremely potentExtremely potentHigh is intense and long lastingHigh is intense and long lastingChronic use can result in serious Chronic use can result in serious
psychiatric, cardiovascular, metabolic and psychiatric, cardiovascular, metabolic and neuromuscular changesneuromuscular changes
ICE: PharmacokineticsICE: Pharmacokinetics
Smoking causes immediate absorptionSmoking causes immediate absorptionBiological half-life around 11 hoursBiological half-life around 11 hours60% metabolized in the liver after 60% metabolized in the liver after
distribution to the braindistribution to the brain40% excreted unchanged40% excreted unchanged
ICE: Effects and ToxicityICE: Effects and Toxicity
Effects similar to cocaineEffects similar to cocainePotent psychomotor stimulants and Potent psychomotor stimulants and
positive reinforcerspositive reinforcersRepeated high doses associated with Repeated high doses associated with
paranoid psychosisparanoid psychosis
ICE: Effects and ToxicityICE: Effects and Toxicity
Many permanent effects due to long-Many permanent effects due to long-lasting abnormal brain chemistries lasting abnormal brain chemistries
Can cause permanent alterations in…Can cause permanent alterations in…Sleep functionsSleep functionsSexual functionsSexual functionsMood (permanent depression)Mood (permanent depression)SchizophreniaSchizophreniaMovement disordersMovement disorders
ICE: Effects and ToxicityICE: Effects and Toxicity
Abnormal brain chemistriesAbnormal brain chemistriesStudies show reduced neuronal density in Studies show reduced neuronal density in
frontal lobe and basal ganglia in abstinent frontal lobe and basal ganglia in abstinent meth users.meth users.
Other Behavioral StimulantsOther Behavioral Stimulants
EphedrineEphedrineMethylphenidate (Ritalin)Methylphenidate (Ritalin)
EphedrineEphedrine
In the news recentlyIn the news recentlySteve BechlerSteve Bechler
Increases NE in the synapseIncreases NE in the synapse Increases BPIncreases BPWeight LossWeight Loss
Methylphenidate (Ritalin)Methylphenidate (Ritalin)
Mechanism similar to cocaineMechanism similar to cocaineAlso studies show it increases dopamine Also studies show it increases dopamine
like amphetaminelike amphetamineUsed for ADHDUsed for ADHDCan be taken IV with cocaine like rushCan be taken IV with cocaine like rush
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