Cocaine & Amphetamines

1. Cocaine & Amphetamines

2. 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.

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

4. 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 1960’s • Inexpensive “crack” cocaine use spread in the late 1970’s

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

7. 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

9. 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

10. 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)

13. 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

14. 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

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

16. 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

17. 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

18. 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

20. 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

21. 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

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

23. 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

24. 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

25. 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

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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

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

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

35. Amphetamines - Background • 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 • 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 • Behavioral stimulation and increased motor activity result from stimulation of dopamine receptors in the mesolimbic system

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

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

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

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

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

42. 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

43. 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

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

45. 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

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

47. 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

48. 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

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

50. 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