1. Cocaine & Amphetamines

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

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

4. Early Years Cont. Cocaine incorporated into numerous medicines and beverages Cocaine incorporated into numerous medicines and beverages Coca-Cola Coca-Cola Harrison Narcotic Act banned its use in 1914 Harrison Narcotic Act banned its use in 1914 Recreational use increased dramatically in the late 1960’s Recreational use increased dramatically in the late 1960’s Inexpensive “crack” cocaine use spread in the late 1970’s Inexpensive “crack” cocaine use spread in the late 1970’s

6. Statistics In 1985 – Estimated 5.7 million users In 1985 – Estimated 5.7 million users In 1997 – Estimated 1.5 million users In 1997 – Estimated 1.5 million users Use in high schools increasing Use in high schools increasing

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

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

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

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

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

15. Pharmacokinetics Distribution Distribution Penetrates brain rapidly Penetrates brain rapidly Brain concentrations far exceed plasma levels Brain concentrations far exceed plasma levels Freely crosses the placental barrier Freely crosses the placental barrier

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

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

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

20. Mechanism of Action Behavior-reinforcing properties Behavior-reinforcing properties Dopamine is the key NT for reinforcement 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. 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 Increased density of D3 receptors in OD victims Responsible for craving Responsible for craving

21. Effects of Short Term Use Low dose, nontoxic physiological responses include Low dose, nontoxic physiological responses include Increased alertness Increased alertness Motor hyperactivity Motor hyperactivity Tachycardia Tachycardia Pupillary dilation Pupillary dilation Increased glucose availability Increased glucose availability Shifts of blood flow from internal organs to muscles Shifts of blood flow from internal organs to muscles

22. Effects of Short Term Use Psychological Effects Psychological Effects Immediate euporia Immediate euporia Giddiness Giddiness Enhanced self-consciousness Enhanced self-consciousness Forceful boastfulness Forceful boastfulness These last approx 30 min. These last approx 30 min.

23. Effects of Short Term Use Moderate euphoria lasts for 60-90 min Moderate euphoria lasts for 60-90 min A state of anxiety lasts for hours A state of anxiety lasts for hours Thoughts race, rapid speech Thoughts race, rapid speech Sleep delayed Sleep delayed Appetite suppressed Appetite suppressed A depressive state follows A depressive state follows

24. Effects of Short Term Use Effects in the CNS Effects in the CNS Depletion of Oxygen Depletion of Oxygen Cerebral Atrophy Cerebral Atrophy Seizures Seizures Others Others Numerous cardiovascular complications can occur with prolonged or single use Numerous cardiovascular complications can occur with prolonged or single use

25. Toxic and Psychotic Effects of Long-Term, High Dose Use Anxiety and sleep deprivation increase Anxiety and sleep deprivation increase Hypervigilance Hypervigilance Suspiciousness, paranoia, and persecutory fears Suspiciousness, paranoia, and persecutory fears Toxic Paranoid Psychosis Toxic Paranoid Psychosis Altered perception of reality that can result in aggressive or homicidal actions as a response to imagined persecution Altered perception of reality that can result in aggressive or homicidal actions as a response to imagined persecution

26. Medical Complications Many cardiovascular effects Many cardiovascular effects Heart attacks Heart attacks Irregular heart rhythm Irregular heart rhythm Respiratory failure Respiratory failure Seizures Seizures

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

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

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

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

31. Treatment There is no consensus on a generally accepted successful pharmacological treatment. There is no consensus on a generally accepted successful pharmacological treatment. Three problems that complicate therapy Three problems that complicate therapy 1. Intensity of the drug effect and reinforcing action 2. Pronounced tendency toward relapse 3. Most addicts have a coexisting disorder

32. Treatment Three areas of need for pharmacologic intervention Three areas of need for pharmacologic intervention 1. Antiwithdrawal agents to restore the dopaminergic tone of the limbic system 2. Anticraving agents that block limbic dopaminergic receptors 3. Treatment of coexisting disorders

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

34. Amphetamines - Background Used for over 60 years therapeutically for numerous disorders Used for over 60 years therapeutically for numerous disorders Schizophrenia Schizophrenia Addictions (morphine and nicotine) Addictions (morphine and nicotine) Head Injury Head Injury Hypotension Hypotension Severe hiccups Severe hiccups Others Others

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

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

37. Pharmacological Effects Physiological Effects Physiological Effects Increased BP Increased BP Decreased HR Decreased HR Increased alertness Increased alertness Psychomotor stimulant Psychomotor stimulant Loss of appetite Loss of appetite

38. Pharmacological Effects Psychological Effects Psychological Effects Euphoria Euphoria Excitement Excitement Mood elevation Mood elevation Increased motor/speech activity Increased motor/speech activity Feeling of power Feeling of power

39. Pharmacological Effects More effects More effects Task performance may improve Task performance may improve Dexterity deteriorates Dexterity deteriorates

40. Pharmacological Effects Metabolized in the liver Metabolized in the liver Excreted through the urine Excreted through the urine Detectable for up to 48 hours Detectable for up to 48 hours

41. Pharmacological Effects At moderate doses At moderate doses Respiratory stimulation Respiratory stimulation Slight tremors Slight tremors Restlessness Restlessness Greater increase in motor activity Greater increase in motor activity Insomnia Insomnia Agitation Agitation

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

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

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

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

46. Dependence and Tolerance Tolerance develops rapidly Tolerance develops rapidly Necessitates the need for markedly higher doses Necessitates the need for markedly higher doses Tolerance to the euphoriant effects develops which causes prolonged binging Tolerance to the euphoriant effects develops which causes prolonged binging

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

48. ICE: Pharmacokinetics Smoking causes immediate absorption Smoking causes immediate absorption Biological half-life around 11 hours Biological half-life around 11 hours 60% metabolized in the liver after distribution to the brain 60% metabolized in the liver after distribution to the brain 40% excreted unchanged 40% excreted unchanged

49. ICE: Effects and Toxicity Effects similar to cocaine Effects similar to cocaine Potent psychomotor stimulants and positive reinforcers Potent psychomotor stimulants and positive reinforcers Repeated high doses associated with paranoid psychosis Repeated high doses associated with paranoid psychosis

50. ICE: Effects and Toxicity Many permanent effects due to long- lasting abnormal brain chemistries Many permanent effects due to long- lasting abnormal brain chemistries Can cause permanent alterations in… Can cause permanent alterations in… Sleep functions Sleep functions Sexual functions Sexual functions Mood (permanent depression) Mood (permanent depression) Schizophrenia Schizophrenia Movement disorders Movement disorders

51. ICE: Effects and Toxicity Abnormal brain chemistries Abnormal brain chemistries Studies show reduced neuronal density in frontal lobe and basal ganglia in abstinent meth users. Studies show reduced neuronal density in frontal lobe and basal ganglia in abstinent meth users.

52. Other Behavioral Stimulants Ephedrine Ephedrine Methylphenidate (Ritalin) Methylphenidate (Ritalin)

53. Ephedrine In the news recently In the news recently Steve Bechler Steve Bechler Increases NE in the synapse Increases NE in the synapse Increases BP Increases BP Weight Loss Weight Loss

54. Methylphenidate (Ritalin) Mechanism similar to cocaine Mechanism similar to cocaine Also studies show it increases dopamine like amphetamine Also studies show it increases dopamine like amphetamine Used for ADHD Used for ADHD Can be taken IV with cocaine like rush Can be taken IV with cocaine like rush