Cocaine

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Cocaine Amphetamines
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Cocaine Background Info

• From the leaves of Erythroxylan coca
• Ancient use in S. America
• Religious, Social, Euphoriant, and Medicinal
• Active alkaloid 1st purified from the leaves in
  1860 What we commonly know as Cocaine.

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Early Years

• Proven to be one of the 1st local anesthetics for
  surgery
• Sigmund Freud obtained and studied cocaines
  psychological effects
• Advocated its use and prescribed cocaine for
  depression and chronic fatigue.
• Later he realized its adverse side effects

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Early Years Cont.

• Cocaine incorporated into numerous medicines and
  beverages
• Coca-Cola
• Harrison Narcotic Act banned its use in 1914
• Recreational use increased dramatically in the
  late 1960s
• Inexpensive crack cocaine use spread in the
  late 1970s

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Statistics

• In 1985 Estimated 5.7 million users
• In 1997 Estimated 1.5 million users
• Use in high schools increasing

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Forms of Cocaine

• E. coca contains about 0.5-1.0 cocaine
• Leaves are soaked in kerosene and gasoline and
  mashed
• Cocaine extracted in the form of coca paste
• Paste approx 50-60 purity

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Cocaine Hydrochloride

• Paste is treated with numerous chemicals to
  oxidize and purify the paste to form the water
  soluble cocaine hydrochloride powder.
• Can be close to 100 pure
• Can be injected, inhaled as powder, or ingested
  orally
• Cannot be smoked

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Freebase Form

• A.k.a. Crack Cocaine
• Similar to the unpurified insoluble coca paste.
• Made by reversing the oxidation process
• Cannot be inhaled (as powder) or injected because
  it is not water soluble
• Forms a stable vapor when heated and inhaled
  (smoked)

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Pharmacokinetics

• Absorption (Cocaine HCl)
• Absorbed from all sites of application
• Mucous membranes, lungs, stomach
• Vasoconstrictor
• crosses mucosal membrane poorly
• Plasma levels peak 30-60 minutes
• Nasal Inhalation causes slow absorption which
  allows for prolonged euphoric effect

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Pharmacokinetics

• IV injection
• Bypasses all barriers to absorption
• Total dosage goes into blood stream and
  eventually the brain
• Smoking Cocaine Base
• Absorption is rapid and complete at the lungs
• Effects onset in seconds, peaks in 5 minutes and
  lasts about 30 minutes

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Pharmacokinetics

• Distribution
• Penetrates brain rapidly
• Brain concentrations far exceed plasma levels
• Freely crosses the placental barrier

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Pharmacokinetics

• Metabolism Excretion
• Half-life 30-90 min.
• Metabolized by enzymes in both plasma and liver
• Slowly removed from brain
• Positive urine tests for 12 hours
• Major metabolite is benzoylecognine

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Use With Alcohol

• In the presence of ethanol a different metabolite
  is produced cocaethylene
• Cocaethylene has the same physiological effect on
  the brain as cocaine but more toxic
• Euphoric effects last longer
• Increases risk of dual dependency
• Increases severity of withdrawal
• Alcohol/Cocaine is the largest two drug
  combination resulting in death

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Mechanism of Action

• Dopaminergic Actions
• Potentiates the synaptic actions of dopamine,
  norepinephrine and serotonin
• Cocaine attaches to and blocks presynaptic
  dopamine reuptake transport proteins
• Dopamine stays in the synapse longer

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Mechanism of Action

• Behavior-reinforcing properties
• Dopamine is the key NT for reinforcement
• Studies show cocaine increases sensitivity of D3
  dopamine receptors in nucleus accumbens and other
  parts of the mesolimbic system important for
  behavior reinforcment.
• Increased density of D3 receptors in OD victims
• Responsible for craving

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Effects of Short Term Use

• Low dose, nontoxic physiological responses
  include
• Increased alertness
• Motor hyperactivity
• Tachycardia
• Pupillary dilation
• Increased glucose availability
• Shifts of blood flow from internal organs to
  muscles

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Effects of Short Term Use

• Psychological Effects
• Immediate euporia
• Giddiness
• Enhanced self-consciousness
• Forceful boastfulness
• These last approx 30 min.

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Effects of Short Term Use

• Moderate euphoria lasts for 60-90 min
• A state of anxiety lasts for hours
• Thoughts race, rapid speech
• Sleep delayed
• Appetite suppressed
• A depressive state follows

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Effects of Short Term Use

• Effects in the CNS
• Depletion of Oxygen
• Cerebral Atrophy
• Seizures
• Others
• Numerous cardiovascular complications can occur
  with prolonged or single use

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Toxic and Psychotic Effects of Long-Term, High
Dose Use

• Anxiety and sleep deprivation increase
• Hypervigilance
• Suspiciousness, paranoia, and persecutory fears
• Toxic Paranoid Psychosis
• Altered perception of reality that can result in
  aggressive or homicidal actions as a response to
  imagined persecution

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Medical Complications

• Many cardiovascular effects
• Heart attacks
• Irregular heart rhythm
• Respiratory failure
• Seizures

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Tolerance and Sensitization

• Tolerance to the high often occurs due to
  downregulation
• Sensitization of the anesthetic and convulsant
  effects occurs
• Explains some deaths occurring after low doses

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Comorbidity

• Chronic cocaine use produces virtually every
  psychiatric syndrome
• 300 abusers
• 56 met current criteria
• 73 met lifetime criteria
• Alcoholism and Heroin addiction extremely high in
  cocaine users

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Cocaine and Pregnancy

• Many indirect effects from the vasoconstriction
  of mothers blood vessels
• Decreased blood flow and oxygen to Uterus
• Associated with
• Placental detachment
• Preterm labor
• Stillbirth
• Low birth weight
• Others

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Cocaine and Pregnancy

• Direct effects from cocaine in the fetus
• Neonatal neurological syndrome
• Abnormal sleep patterns, tremors, seizures
• Increased incidence of SIDS
• Cocaine impaired children show difficulty
  developing attachments, dealing with multiple
  stimuli, aggression
• High incidence of ADHD

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Treatment

• There is no consensus on a generally accepted
  successful pharmacological treatment.
• Three problems that complicate therapy
• Intensity of the drug effect and reinforcing
  action
• Pronounced tendency toward relapse
• Most addicts have a coexisting disorder

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Treatment

• Three areas of need for pharmacologic
  intervention
• Antiwithdrawal agents to restore the dopaminergic
  tone of the limbic system
• Anticraving agents that block limbic dopaminergic
  receptors
• Treatment of coexisting disorders

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Treatment

• Psychosocial treatment offers the most promise
• Cocaine Anonymous
• Individual/Group counseling
• Cognitive behavioral therapy
• Psychodynamic therapy
• Behavior Reinforcement strategies

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Amphetamines - Background

• Used for over 60 years therapeutically for
  numerous disorders
• Schizophrenia
• Addictions (morphine and nicotine)
• Head Injury
• Hypotension
• Severe hiccups
• Others

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Amphetamines - Background

• Used in WW II to fight fatigue and enhance
  performance
• Widespread abuse began in 1940s with students
  and truck drivers to stay awake and increase
  alertness
• Were used as appetite suppressants

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Mechanism of Action

• All CNS effects caused by the release of newly
  synthesized NE and dopamine from presynaptic
  storage sites
• Behavioral stimulation and increased motor
  activity result from stimulation of dopamine
  receptors in the mesolimbic system

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Pharmacological Effects

• Physiological Effects
• Increased BP
• Decreased HR
• Increased alertness
• Psychomotor stimulant
• Loss of appetite

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Pharmacological Effects

• Psychological Effects
• Euphoria
• Excitement
• Mood elevation
• Increased motor/speech activity
• Feeling of power

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Pharmacological Effects

• More effects
• Task performance may improve
• Dexterity deteriorates

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Pharmacological Effects

• Metabolized in the liver
• Excreted through the urine
• Detectable for up to 48 hours

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Pharmacological Effects

• At moderate doses
• Respiratory stimulation
• Slight tremors
• Restlessness
• Greater increase in motor activity
• Insomnia
• Agitation

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Pharmacological Effects

• At high doses
• Repetitive purposeless acts
• Sudden outbursts of aggression/violence
• Paranoid delusions
• Severe anorexia
• Overall psychosis and abnormal mental conditions
• Amphetamine Psychosis paranoid ideation
• Primarily with meth users

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Pharmacological Effects

• In addition to the direct effects of the drug.
• Infections from neglected health care
• Poor eating habits
• Use of unsterile equipment
• Great deterioration in social, personal,
  occupational affairs

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Pharmacological Effects

• Long Term evidence shows...
• Psychometric deficits
• Poor academic performance
• Behavioral problems
• Cognitive slowing
• General maladjustment
• The effects on this list are permanent.

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Dependence and Tolerance

• Use becomes compulsive
• Drug strongly effects areas of brain associated
  with behavior reinforcement
• Physical dependence follows a classical
  conditioning model
• Withdrawal occurs but not as dramatic as with
  narcotics and barbiturates
• Symptoms opposite of drugs effects

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Dependence and Tolerance

• Tolerance develops rapidly
• Necessitates the need for markedly higher doses
• Tolerance to the euphoriant effects develops
  which causes prolonged binging

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ICE

• Freebase form of methamphetamine
• Extremely potent
• High is intense and long lasting
• Chronic use can result in serious psychiatric,
  cardiovascular, metabolic and neuromuscular
  changes

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ICE Pharmacokinetics

• Smoking causes immediate absorption
• Biological half-life around 11 hours
• 60 metabolized in the liver after distribution
  to the brain
• 40 excreted unchanged

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ICE Effects and Toxicity

• Effects similar to cocaine
• Potent psychomotor stimulants and positive
  reinforcers
• Repeated high doses associated with paranoid
  psychosis

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ICE Effects and Toxicity

• Many permanent effects due to long-lasting
  abnormal brain chemistries
• Can cause permanent alterations in
• Sleep functions
• Sexual functions
• Mood (permanent depression)
• Schizophrenia
• Movement disorders

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ICE Effects and Toxicity

• Abnormal brain chemistries
• Studies show reduced neuronal density in frontal
  lobe and basal ganglia in abstinent meth users.

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Other Behavioral Stimulants

• Ephedrine
• Methylphenidate (Ritalin)

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Ephedrine

• In the news recently
• Steve Bechler
• Increases NE in the synapse
• Increases BP
• Weight Loss

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Methylphenidate (Ritalin)

• Mechanism similar to cocaine
• Also studies show it increases dopamine like
  amphetamine
• Used for ADHD
• Can be taken IV with cocaine like rush