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Understanding Substance Use Disorders

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The teenager who can really hold their liquor is most at risk of alcoholism. ... Exception or rule? Journal of Dual Diagnosis. 3(1)(pp 33-58), ... – PowerPoint PPT presentation

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Title: Understanding Substance Use Disorders


1
Understanding Substance Use Disorders  
  • Jean J. Bonhomme M.D., M.P.H.
  • Assistant Professor, Morehouse School of
    Medicine
  • Department of Psychiatry
  • jbonhomme_at_msm.edu

2
Role of the Pediatrician
  • Most substance use disorders actually begin in
    the pediatric age group.
  • Few people start smoking after age 26.
  • Cigarette and liquor advertising targets young
    people
  • Peer group pressure to use is common.
  • The teenager who can really hold their liquor
    is most at risk of alcoholism.
  • Family history is an important risk factor.

3
The CDC's Best Practices for Comprehensive
Tobacco Control Programs (1999)
  • Most people begin using tobacco in early
    adolescence, typically by age 16
  • Children buy the most heavily advertised brands,
    and are three times more affected by advertising
    than adults.
  • Smoking prevalence is higher among adults living
    below the poverty level (32.3 percent) than for
    those living at or above the poverty level (23.5
    percent).
  • (Source Oral Cancer Foundation)

4
Morehouse School of Medicine
  • Morehouse Presidents David Satcher, Louis
    Sullivan, and James Gavin (2004)
  • Tobacco companies actively target minority youth
    using
  • Tobacco ads and products placed at childrens eye
    level in retail outlets
  • Fruit flavored tobacco products
  • Hip-hop packaging

5
Cultural factors impacting this group
  • Include family, media and community role models
  • Social acceptability of tobacco
  • Tobacco as a gateway drug
  • Image (looking grown up, sexy)
  • Tobacco as a vehicle for other drugs (marijuana,
    crack, etc.) and
  • Tobacco as self medication / stress relief.

6
Morehouse Presidents
  • Called for the tobacco companies to remove these
    products from the shelves.
  • Tobacco companies refused, stating that they had
    met the terms of the tobacco settlement.
  • There is a pressing need for effective policy and
    informational countermeasures targeting this
    vulnerable population to promote tobacco
    avoidance and to encourage tobacco cessation.

7
Signs of Drug use by Children
  • Direct drug effects and signs on P.E., e.g.
    abnormal pupil size or needle marks, red eves,
    weight loss
  • Unexplained increase in truancy and / or lateness
    to classes
  • Sudden decrease in academic performance
  • New onset behavioral problems in schoolLoss if
    interest in previously enjoyed activities
  • Hanging out in a new crowd and dropping old
    friends
  • Personality changes, e.g. new onset social
    withdrawal, becoming fidgety or listless

8
Signs of Drug use by Children
  • Sudden unexplained mood changes, e.g. depression,
    edginess, suspiciousness or paranoia
  • Memory problems
  • Increased secretiveness and withdrawal from
    family
  • Increased combativeness
  • Sleep problems, fatigue or hyperactivity
  • Higher index of suspicion if a positive family
    history of alcoholism or addiction is noted

9
Addiction vs. Dependence an
important new distinction
  • Source Principles of Addiction Medicine, 3rd
    Edition American Society of
    Addiction Medicine

10
Addiction Defined
  • Addiction is defined as continued substance use
    in the face of adverse consequences.
  • Extreme compulsion is the overriding feature.
  • Examples - Using drugs and/or alcohol to the
    point of intoxication and grossly impaired
    function, e.g. a person gets arrested for
    drunken driving and their license is confiscated.
  • Two days later they are on the road again and
    drunk. Punishment appears to be no deterrent.
  • Key In the presence of the substance,
    function deteriorates, but use continues.

11
Dependence Defined
  • Dependence is very different - defined as a
    state in which the body relies on a substance
    for normal functioning.
  • Example A person has a ruptured disk in the
    lower back, with pain is so severe that they
    cannot work or take care of their children.
  • When they are given an opiate pain medication,
    the pain is reduced to the point where they
    can function normally and responsibly.
  • Key In the presence of the substance,
    function normalizes.

12
What is the Importance of This
Distinction?
  • DSM-IV does not make any distinction here.
  • Usually neither do the criminal courts.
  • In both instances, the person really needs the
    substance, but the consequences of their use are
    completely different.
  • Not making this distinction lumps persons with a
    legitimate need for a controlled substance
    together with those who are actively misusing
    them.
  • A crucial distinction between people who are
    being helped and those who are harming themselves
    and others by their drug use.
  • Example Sickle Cell patient in ER.

13
Brain Areas In Addiction N. Accumbens and VTA
14
Brain Areas In AddictionPrefrontal Cortex
15
Brain Areas In DependenceBrainstem and Thalamus
16
The Anatomy Underlying This Distinction
  • Addiction is clearly a brain disease.
  • Different parts of the brain are responsible for
    addiction (versus dependence) to opiates.
  • The areas in the brain underlying addiction to
    morphine are the reward pathway (including the
    VTA, nucleus accumbens, and prefrontal cortex).
  • All drugs of addiction appear to involve the
    reward pathway.
  • Those areas underlying dependence to morphine are
    the thalamus and brainstem.

17
Dependence Explained
  • It is possible to be dependent without being
    addicted, a very important distinction.
  • This is especially true for people being treated
    chronically with opiates, e.g. pain
    associated with terminal cancer.
  • They may be dependent - if the drug is
    stopped, they suffer recurrence of pain and a
    withdrawal syndrome. However, they are not
    compulsive users.
  • However, if one is addicted, they are most
    likely dependent as well.

18
Dependence Explained
  • Not every dependent person is an addict, not
    even those who need very high doses of
    medication.
  • Most people treated with opiates are unlikely
    to become addicted, for example in a hospital
    setting for pain control after surgery.
  • Although they may feel some euphoria although
    pain relief and sedating effects predominate.
  • There is no pattern of compulsive use and the
    prescribed use is short-lived.

19
Why Did DSM-IV Fail to Make This
Distinction?
  • There was some debate as to whether compulsive
    substance use leading to adverse consequences
    should be called addiction or dependence.
  • It was felt by some that the term addiction was
    too pejorative and prejudicial, such that persons
    with a diagnosis of addiction would be very
    harshly judged.
  • The term dependence was felt to be much less
    prejudicial, so by one vote, it was decided to
    use the term dependence.
  • This has led to much confusion. Plans exist
    currently to change terminology for DSM-V.

20
So How Do We Define Substance Abuse?
  • In drug abuse, function may deteriorate in the
    presence of the drug and other adverse
    consequences may ensue, but there is no
    compulsion to continue using the drug.
  • Example A person uses a drug for recreational
    purposes for some time, then has a bad
    experience, such as an overdose or a brush with
    the law. They say Thats it Im through
    with this stuff.
  • This is not addiction, because they voluntarily
    left it alone when it clearly became more
    trouble than its worth.
  • A true addict cannot do this.

21
Tolerance Explained
  • Tolerance is defined as progressively decreasing
    response to a drug with exposure. Increased doses
    are necessary to get the same effect.
  • This usually refers to repeated or prolonged
    exposure, which is called chronic tolerance.
  • Rarely, sensitivity to a drug may increase with
    repeated exposure, called reverse tolerance.
  • Having high tolerance and needing high doses of a
    drug is NOT addiction.

22
Mechanisms of Tolerance
  • Metabolic
  • Due to stimulation of the enzymes that break
    down the drug.
  • Adaptive
  • The body adapts to the presence of the drug
    this is characteristic of most drugs that lead
    to use disorders.
  • The drug must be taken in increasing quantities
    to achieve the same effect.

23
The Withdrawal Syndrome Explained
  • Withdrawal is a group of negative physical and
    mental effects resulting from discontinuation of
    addictive substances by persons who have become
    habituated to their use.
  • Withdrawal symptoms may include severe drug
    cravings as well as a group of negative physical
    symptoms that may occur when a person suddenly
    stops using a drug to which he or she has become
    dependent.
  • Generally, the longer the drugs are taken and
    the higher the dose, the more severe the
    symptoms.

24
The Withdrawal Syndrome Does NOT
Equal Addiction
  • If you give adequate doses of opiates to a
    person in opiate withdrawal, often they can
    resume normal function.
  • After being gradually tapered off,
    most people do not go back to using.
  • By contrast, truly addicted people who
    have been incarcerated for years and are
    long past any remnant of the physical
    withdrawal syndrome may relapse on drugs
    within months, weeks, days or even hours of
    their release.

25
Human Circulatory System Through the Heart Twice

26
Route of Drug Administration and Risk of Addiction
  • Smoking is actually potentially the most
    addictive route of drug administration.
  • Behavioral science has proven that the faster a
    reward or punishment follows an action,
    the greater the impact of that reward or
    punishment on future behavior.
  • When a drug is snorted, it takes 30 to 120
    seconds to get into the blood, and high blood
    levels of the drug are rarely attained.

27
Example Cocaine
  • Snorting requires that the cocaine travels from
    the blood vessels in the nose to the heart (blue
    vessels), where it gets pumped to the lungs
    (blue vessels) to be oxygenated.
  • The oxygenated blood (red vessels) carrying
    the cocaine then travels back to the
    heart where it is pumped out to the organs
    of the body (red vessels), including the brain.

28
Route of Administration and Addiction
Potential
  • When a drug is injected in the arm,
    it takes a long circulatory pathway,
    up the arm, into the right side of the heart,
    into the lungs, into the left side of the heart,
    and into the carotid arteries to the
    brain.
  • High blood levels of the drug are commonly
    attained.
  • This process takes about eighteen seconds.

29
Example Cocaine
  •  
  • Smoking cocaine high addictive liability
  • Historically cocaine abuse involved snorting or
    injecting the powdered form (the hydrochloride
    salt).
  • When cocaine is processed to form the freebase,
    like crack, it can be smoked.
  • Heating the hydrochloride salt form of cocaine
    will destroy it the freebase can be vaporized
    at high temperature without any destruction of
    the compound, leading to much quicker onset of
    action.  

30
Route of Administration and Addiction Potential
  • When a drug is smoked, it takes a short
    circulatory path, into the lungs, into the
    left side of the heart, and into the carotid
    arteries to the brain.
  • Because of the enormous surface area of the
    lungs (roughly the area of a tennis court), high
    blood levels of the drug are commonly attained,
    as is the case with injection.
  • This process takes only about seven seconds.

31
Route of Administration and Addiction Potential
  • If you were training a dog with food rewards,
    which would be most effective in getting the
    animal to repeat the rewarded behavior giving
    the food in seven seconds, in eighteen
    seconds, or in 30-120 seconds?
  • Rapidity of onset of action is strongly
    associated with addictive potential.
  • Consider how hard it is to give up cigarettes,
    or how explosively cocaine addiction grew when
    the smokeable crack form was introduced.

32
Route of Administration and Needle Aversion
  • This is the opposite of what you would think
    because solids seem more substantial than
    liquids, and liquids seem more substantial than
    vapors. However, vapors can actually get into
    the brain the most quickly.
  • Perhaps worst of all, smoking is much more
    socially acceptable behavior than using needles
    or snorting due to our long history of accepting
    tobacco smoking.
  • For this reason, when a drug is presented in
    smokeable form, a major social barrier to
    beginning its use (called needle aversion) is
    removed.

33
Pharmacological Half-Life and
Addiction
  • Half-life is the time it takes for the body to
    eliminate half of the drug from the blood.
  • Drugs with shorter half-lives tend to have
    greater addictive potential than drugs with
    longer half lives because shorter duration of
    action causes a need to take more often.
  • Behavioral science tells us that the more often a
    behavior is practiced, the greater the tendency
    to become habitual.
  • e.g. crack cocaine must be taken every few
    minutes, increases addictive potential.

34
Pharmacological Half-Life and
Addiction
  • Methadone treatment, which only needs to be taken
    once daily to suppress withdrawal is much less
    likely to promote constant drug seeking behavior
    than oxy-contin or heroin, which must be taken
    several times daily to maintain adequate blood
    levels.
  • People addicted to heroin are practicing drug
    seeking / using behavior several times a day,
    every day, day and night.
  • People on methadone take one dose in the
    morning and go about their business for the rest
    of the day.

35
Neurotransmitters 101
  • The Basics

36
Why Discuss Neurotransmitters?
  • They are natural chemical messengers.
  • Nerve cells communicate with each other by
    sending these chemicals across gaps between
    cells, called synapses.
  • Psychoactive drugs create their effects by
    modifying the actions of neurotransmitters
  • Increasing,
  • Decreasing,
  • Blocking,
  • Mimicking, or
  • Otherwise modifying them

37
Key Neurotransmitter Functions
  • Acetylcholine (Ach) thought, movement
  • Dopamine (DA) pleasure, motion
  • Serotonin relaxation, mood
  • Glutamate the brains accelerator pedal
  • Gamma-amino-butryic acid (GABA) the
    brains brake pedal
  • Endorphins (Enkephalins, Dynorphins) the
    brains natural painkillers

38
So With Neurotransmitters, How Does Addiction
Work?
  • By altering neurotransmitter actions, sometimes
    in complex ways, addictive drugs hijack the
    brains reward system.
  • The same areas of the brain that govern our
    natural drives for food, water and sex get taken
    over completely by the drug.
  • Often, addicts will reach a point where they
    can no longer derive pleasure from natural means
    anymore.
  • They may derive pleasure only from the drug, and
    then eventually end up using the drug not even
    feeling pleasure anymore, but just to feel
    reasonably normal.

39
Demographics
  • Who Is Using All These Drugs?

40
The Demographics of Substance Use Disorders
  • The National Survey on Drug Use and Health
  • http//www.oas.samhsa.gov/nhsda.htm
  • An annual survey conducted by the Substance Abuse
    and Mental Health Services Administration
    (SAMHSA)
  • Estimates the prevalence of illicit drug use in
    the United States.
  • Some of the more notable statistics from the 2004
    study follow.

41
Alcohol vs. Drugs
  • In 2004, about 22.5 million Americans aged gt or
    12 reported past year substance abuse or
    dependence (9.4 of the population).
  • Of these, 3.4 million were dependent on or
    abused both alcohol and illicit drugs.
  • 3.9 million were dependent on or abused
    illicit drugs but not alcohol, and
  • 15.2 million were dependent on or abused
    alcohol but not illicit drugs.
  • 19.1 million Americans were current substance
    users (used at least once during the 30
    days prior to the interview.)

42
Cocaine, Hallucinogens, MDMA and Marijuana Use
  • There were 2.0 million current cocaine users,
    467,000 of whom used crack.
  • Hallucinogens were used by 929,000 people
  • There were an estimated 166,000 heroin users.
  • There were an estimated 450,000 Ecstasy (MDMA)
    users.
  • Marijuana is the most commonly used illicit drug,
    with a rate of 6.1 of the population (14.6
    million current users).

43
Nonmedical Use of Psychotherapeutic Medications
  • In 2004, 6.0 million persons were current users
    of painkillers or psychotherapeutic drugs taken
    nonmedically (2.5 of the population).
  • These include 4.4 million who used pain
    relievers,
  • 1.6 million who used tranquilizers,
  • 1.2 million who used stimulants, and
  • 0.3 million who used sedatives.

44
Employment Status and Drug Use
  • In 2004, 19.2 of unemployed adults aged 18
    or older were current illicit drug users
    compared with
  • 8.0 of those employed full time and
  • 10.3 of those employed part time.
  • However, of the 16.4 million illicit drug
    users aged 18 or older in 2004, 12.3
    million (75.2) were employed either full
    or part time.

45
Ethnicity and Drug Use Dispelling the Myths
  • In 2004, 7.9 of the population aged 1217
    years reported current illicit drug use .
  • Breakdown by racial/ethnic group
  • 26.0 Native American / Alaskan youths
  • 12.2 for Biracial or Multiracial youths
  • 11.1 for White youths,
  • 10.2 for Latino youths,
  • 9.3 for African-American youths,
  • and 6.0 for Asian youths.

46
Mortality and Morbidity of Untreated Opiate
Addiction
  • Untreated heroin addicts suffer a death rate
    thirteen times that of the general population.
  • More so today than ever, heroin is not
    the only opiate contributing to the landscape
    of addiction.
  • Excess deaths and illnesses occur from a wide
    variety of causes, including but not limited to
  • Drug effects, overdoses and interactions,
  • Intentional and unintentional injuries
  • Infectious diseases.

47
The economic costs of heroin addiction in the
United States
  • Mark T L Woody et al (2001)
  • We estimate that the cost of heroin addiction in
    the United States was 21.9 billion in 1996.
  • Of these costs, productivity losses accounted for
    11.5 billion (53), criminal activities 5.2
    billion (24), medical care 5.0 billion (23),
    and social welfare 0.1 billion (0.5).
  • This economic burden highlights the
    importance of investment in prevention and
    treatment.

48
Is the Problem of Opiate Addiction Likely to
Increase?
  • Increasing purity of heroin has been reported in
    the Southeastern U.S. up to 70 pure on the
    streets of Atlanta. Purity is catching up with
    the Northeastern U.S.
  • Increasing availability of Pharmaceutical opiates
    12 year olds have ordered Oxy-contin
    from offshore sites via internet.
  • Newer opiates Oxy-Contin, Fentanyl, etc.
  • Effective non-injection delivery systems
    smoking, snorting, eating the contents of
    fentanyl patches.

49
Drugs and the Law
50
Ethnicity and Differential Sentencing for Drug
Possession
  • Differential sentencing for drug possession based
    on the form of drug commonly used by specific
    ethnic groups has dramatically increased the
    proportion of incarcerated ethnic minorities
    (Braithwaite Arriola, 2009).
  • African Americans and Latinos tend to use cocaine
    in crack form rather than as powder.
  • However, crack is simply cocaine powder processed
    by cooking with common baking soda (making a
    crackling sound, hence the name), but
    possession of crack typically incurs a much
    harsher sentence.

51
Is a Sentencing Differential of This Magnitude
Rational or Justifiable?
  • Federal guidelines a mandatory minimum five-year
    sentence to a maximum of twenty years for
    possession of five grams of crack (the weight of
    only two pennies).
  • However, five grams of powder cocaine incurs only
    a misdemeanor with no mandatory minimum sentence
    and a maximum penalty of one year
    in jail.
  • Half a kilo of powder cocaine is required to
    carry the same penalty as possession of only
    five grams of crack, the latter having a much
    greater street value and which could be readily
    converted into crack.

52
According to U.S. District Judge Clyde S. Cahill
of Missouri
  • Federal guidelines for possession of crack
    have been directly responsible for
    incarcerating nearly an entire generation of
    young black American men.
  • The U.S. Sentencing Commission reported that the
    racial breakdown of cocaine powder convictions in
    2000 was 17.8 percent white, 30.5 percent black,
    and 50.8 percent Latino.
  • During the same year, the distribution of crack
    cocaine convictions was 5.6 percent white
    defendants, 84.7 percent black, and 9.0
    percent Latino, a conviction rate 15 times
    greater for blacks than for whites.

53
Klein, S., Petersilia, J., Turners, S. (1990,
February 13). Race and imprisonment decisions
in California. Science, 247, 812-816.
  • A 1990 RAND study found that while defendants in
    California received generally comparable
    sentences for comparable offenses regardless of
    race, this was not the case with respect to
    drug offenses.
  • These policy changes resulted in a significant
    increase in drug offenders sentenced to prison as
    well as longer prison terms.

54
Mumola, C., Beck, A. (1997). Prisoners
in 1996. Washington, DC
U. S. Department of Justice,
Bureau of Justice Statistics.
  • Overall, the number of black drug offenders
    sentenced to prison increased by 707 between
    1985 and 1995, while the number of white drug
    offenders increased by 306.
  • Drug offenses accounted for 42 of the rise in
    the African-American state prison population
    compared with 26 of the rise in the white state
    prison population during that same 10-year period.

55
Federal Sentencing
  • Federal sentencing guideline penalties for
    crack cocaine offenses generally are three to
    six times as long as the penalties for powder
    cocaine offenses involving equivalent quantities
    of the same basic chemical substance.
  • Advocates for social justice and equity consider
    such sentencing guidelines to be a form of
    racial profiling and racial discrimination.

56
Drug Properties
  • Part I Drugs Not Commonly Thought
    of as Drugs

57
Nicotine
  • Nicotine shows structural similarities
    to neurotransmitters, explaining its
    addictive properties. 

                   Nicotine
58
Nicotine
  • Nicotine works by linking to a group of receptors
    that bind the neurotransmitter acetylcholine.
  • Nerve cells activated by acetylcholine are caled
    cholinergic neurons.
  • Most of these neurons use acetylcholine to
    communicate to other neurons in many different
    brain regions at the same time.

59
Nicotine
  • The resulting increased release of acetylcholine
    leads to heightened activity in acetylcholine
    pathways throughout the brain, calling the body
    and brain to action.
  • Many smokers use this as a wake-up call to
    re-energize throughout the day.
  • Nicotine improves reaction time and ability to
    pay attention, leading to the subjective
    perception of being able to work better.

60
Nicotine
  • Stimulation of cholinergic neurons by nicotine
    also promotes the release of the neurotransmitter
    dopamine in the brains reward pathways as well.
  • brings on pleasant, happy feelings
  • encourages repeating the nicotine- seeking
    actions again and again.
  •  

61
Nicotine
  • The brain also makes more endorphins in
    response to nicotine. Endorphins are the
    body's natural pain killers, with a chemical
    structure very similar to that of heavy-duty
    opioid painkillers like morphine, and can
    contribute to feelings of euphoria.
  • Chronic users of tobacco products typically
    have markedly increased numbers of nicotine
    receptor sites in their brains. This explains
    in part their intense craving.

62
Nicotine
  • Nicotine also causes the release of the
    neurotransmitter glutamate, which is involved in
    learning and memory.
  • Glutamate enhances connections between sets
    of neurons, perhaps forming the physical basis of
    memory in general.
  • Nicotine may lead to a glutamate-induced memory
    loop of the pleasant feelings associated with
    nicotine use and further drive the desire to use
    nicotine.

63
Alcohol Kinetics(Behavior in the Body)
  • Alcohol is certainly one of the most widely
    used drugs in the world.
  • Extensively studied
  • Unique and interesting pharmacology
  • After ingestion by mouth, alcohol is
    absorbed almost completely from the
    duodenum (the first section of the small
    intestine).
  • The rate of absorption is extremely variable
    depends on several factors

64
Alcohol
  • Volume, type and alcohol concentration of
    the beverage
  • Less concentrated solutions are absorbed
    more slowly.
  • However very concentrated solutions can
    inhibit emptying of the stomach.
  • Carbonation can increase the absorption of
    alcohol.
  • Rate of ingestion is important
  • The faster you drink,
    the faster the absorption

65
Alcohol
  • Food has a major effect on alcohol absorption.
  • High-fat foods can significantly delay
    absorption.
  • The effect of food on alcohol is primarily due to
    the delay in emptying of the stomach that follows
    meal consumption.
  • Stomach and liver metabolism can significantly
    decrease the availability of alcohol and
    thus the amount of alcohol getting into the
    circulation.

66
Key Points in the Metabolism of Alcohol
  • Alcohol to Acetaldehyde to Acetic Acid

              

67
Alcohol Metabolism
  • Metabolism of alcohol occurs primarily in the
    liver in a 2-step process.
  • Step 1 Alcohol is oxidized to acetaldehyde by
    an enzyme-Alcohol DeHydrogenase (ADH).
  • At moderate blood alcohol levels, the rate of
    metabolism is maximum capacity and has a constant
    rate of approximately 7-10 grams per hour
    (equivalent to 1-drink per hour).
  • However, this rate varies greatly between
    individuals and even within the same individual
    from day-to-day.

68
Alcohol Metabolism
  • Step 2 acetaldehyde is converted to acetic acid
    by the enzyme aldehyde dehydrogenase.
  • Normally, acetaldehyde is metabolized very
    rapidly and usually does not accumulate or
    interfere with normal functioning.
  • Large amounts of alcohol may lead to accumulation
    of acetaldehyde, and may cause symptoms like
    headache, gastritis, nausea, dizziness, which
    might contribute to a hangover.

69
Alcohol Metabolism
  • Antabuse (Disulfiram) in the treatment of
    alcoholism acts by blocking aldehyde
    dehydrogenase (ALDH) causing the accumulation of
    acetaldehyde, giving drinking some very aversive
    symptoms
  • Nausea, Vomiting, Flushing, Sweating and Thirst
  • Throbbing Headache and Throbbing in the Neck
  • Respiratory Difficulty, Shortness of Breath,
    Rapid Breathing
  • Chest Pain, Palpitations, and Rapid Heart Beat
  • Hypotension, Syncope and Weakness
  • Marked Uneasiness, Vertigo, Blurred Vision
    and Confusion

70
Racial Genetic Variation in Alcohol Metabolizing
Enzymes
  • 50 of Asian populations (including Chinese,
    Japanese, Taiwanese, Korean) have a variation in
    Aldehyde DeHydrogenase (called ALDH22) that
    causes much slower elimination of acetaldehyde.
  • As a result, they get an Antabuse-like reaction
    with flushing and nausea in response to alcohol,
    making alcohol very aversive to these
    individuals.
  • The prevalence of alcoholism is almost zero in
    persons with the ALDH22 allele.

71
Alcohol Behaves Somewhat Differently in the
Genders
  • Alcohol is distributed into total body water.
  • Gender differences in body composition
  • Women have a lower proportion of total body
    water compared to men.
  • If a woman and a man of equal weight consume the
    same amount of alcohol, the womans blood
    alcohol levels would come out to be higher than
    the mans.
  • Women can be alcoholic and suffer liver damage at
    what would be considered a moderate consumption
    level for a man.

72
Alcohol Behaves Somewhat Differently in the
Genders
  • There are gender differences in bodily
    distribution of alcohol due to differences in
    body composition and total body water.
  • Women have higher alcohol elimination rates per
    body weight, possibly related to
  • Larger liver volumes per unit lean body mass
    seen in women, and / or
  • Gender differences in ADH activity.
  • There appears to be no effect of the menstrual
    cycle on alcohol kinetics.
  • Studies on the effect of oral contraceptives on
    alcohol kinetics show conflicting results.
  •  

73
Alcohol Drug Effects
  • Alcohol acts as a central nervous system
    depressant.
  • Alcohol may falsely appear to be a stimulant
    due to its depression of inhibitory control
    mechanisms in the brain.
  • Characteristic responses to drinking alcohol
    include
  • euphoria,
  • impaired cognitive processes and
  • decreased mechanical efficiency, especially with
    regard to coordination.

74
Blood Alcohol Concentration (BAC)
  • The following dose-response descriptions reflect
    the expected responses in
    non-dependent individuals.
  • Once tolerance develops, threshold concentrations
    at which these effects occur are
    elevated.  
  • At low BACs corresponding to
    1-2 drinks (0.02-0.03)
  • mood elevation
  • slight muscle relaxation

75

Blood Alcohol Concentration (BAC)
  • At progressively increasing blood alcohol
    concentration (BAC) levels, even below the
    legal limit, additional signs and symptoms
    appear       
  • increased relaxation,
  • warmth,
  • increases in reaction time
    (slower response).      

76
Blood Alcohol Concentration (BAC)
  • Around the legal limit of intoxication
    (.08-.10)
  • impairment of balance,
  • impairment of speech, vision, and hearing
  • impairment of muscle coordination,
  • possible feelings of euphoria.

77
Blood Alcohol Concentration (BAC)
  • At very high BACs
  • progressive intoxication,
  • progressive impairment
  • loss of physical and mental control,
  • At levels of 0.40-0.50, the individual
    is in a deep coma and at risk of death from
    impaired breathing responses (respiratory
    depression).

78
Alcohol and Behavior Reinforcement
  • Alcohol is a drug of abuse because the
    effects of alcohol may be strongly reinforcing
    and potentially addictive.
  • An understanding of the mechanisms of
    alcohol action helps explain this.
  • Animal evidence exists to support the
    involvement of alcohol in the brains reward
    system.      

79
Alcohol and Genetics
  • There are animals that have been bred to prefer
    alcohol over water. They show innate differences
    in both brain structure and neurotransmitter
    function and levels compared to animals bred to
    prefer water.
  • Experimental animals have been trained to
    continuously self-administer alcohol with
    intra-cranial cannulae directly inserted into the
    VTA. They will bar-press repeatedly for
    injections of alcohol directly into the VTA.
  • Offspring of human alcoholics are at much higher
    risk of alcoholism as well as addiction to other
    drugs, showing a genetic link.

80
Mechanism of Alcohol Action in the Reward System
  • Alcohol is believed to act by facilitating GABA
    function.
  • Alcohol interacts with the GABA-A receptor, the
    same one that benzodiazepines (Xanax, Valium)
    attach to.
  • Facilitated GABA-A function results in activation
    of the DA neurons in the reward system, and is
    involved in the sedative and anxiety-reducing
    effects of alcohol.
  • Sudden removal or decrease in alcohol results in
    the rebound hyperexcitability seen during
    withdrawal.

81
Alcohol and the Dopamine and Opioid Systems
  • Alcohol does not act directly on DA receptors,
    but acts indirectly to increase DA levels in the
    reward pathway, causing pleasant effects.
  • Alcohol does not act directly on the opioid
    system, but by indirect action results in
    activation of the opioid system.
  • The opioid system is also involved in
    the subjective craving for alcohol.
  • Opioid antagonists, such as naltrexone have
    been demonstrated to block the rewarding effects
    and reduce craving for alcohol.
  •     

82
More On the Drug Therapy of Alcoholism
  • Acamprosate (Campral)
  • Recent FDA approval in the US is a drug, used
    in Europe for some years now
  • Stimulates the GABA inhibitory system and
    antagonizes the glutamate excitatory system.
  • Benzodiazepines (mostly Librium, Valium)
  • Used primarily for detoxification from alcohol
    to treat hyperexcitability, convulsions and
    hallucinations during withdrawal.   
  • Antidepressants (mostly effective
    in patients with coexisting depression).

83
Drug Properties
  • Part II Commonly Recognized Drugs

84
Opiates
  • Opioids have morphine-like actions.
  • Natural opiates are alkaloids found in the
    resin of the opium poppy e.g. morphine,
    codeine and thebaine.
  • Semi-synthetic opiates are chemically altered
    derivatives of natural opioids, e.g.
  • hydromorphone,
  • hydrocodone,
  • oxycodone,
  • oxymorphone,
  • diacetylmorphine (heroin) 
  •   

85
Opiates
  • Fully synthetic opioids are artificial compounds
    with opioid activity, e.g.
  • fentanyl,
  • methadone,
  • tramadol (ultram), and
  • propoxyphene (darvon).

86
Opiates
  • Endogenous opioid peptides are substances
    produced naturally by the body,e.g. endorphins,
    enkephalins, and dynorphins.
  • Morphine is Endorphins evil twin
  •  

87
Opiates
  • Opioids are potentially addictive drugs, although
    not all users become addicted.
  • Factors in addiction include
    the environment, genetics and
    personality of the user.
  • Opioids may produce euphoria
    or pleasurable feelings, acting as
    positive reinforcers by interacting with reward
    pathways in the brain.

88
Opiates
  • Opioids bind to opiate receptors concentrated in
    specific areas within the reward pathway
    (including the VTA, nucleus accumbens,
    and cortex).
  • Morphine also binds to areas involved
    in the pain pathway (including the thalamus,
    brainstem, and spinal cord).
  • Binding of opioids to areas in the pain pathway
    produces analgesia (decreased perception
    of pain).

89
Opiates
  • Brain regions mediating the development of
    morphine dependence involve specific areas
    separate from the reward pathway, the thalamus
    and the brainstem.
  • The parts of the reward pathway involved in
    heroin or morphine addiction were shown for
    comparison.
  • Many of the withdrawal symptoms from heroin or
    morphine are generated when the opiate
    receptors in the thalamus and brainstem are
    deprived of morphine.
  •  

90
Cocaine
  • Cocaine
  • Cocaine reaches all areas of the brain, but
    it binds especially to the reward areas that are
    rich in dopamine synapses such as the VTA
    and the nucleus accumbens.

91
Cocaine Addiction and
Reward Pathway Activation
  • Cocaine binding in another area, the caudate
    nucleus (which affects movement and is affected
    in Parkinsons disease) can explain motor
    effects such as increased stereotypic (or
    repetitive) behaviors (pacing, nail-biting,
    scratching, etc.).
  • The reward pathway can be activated even in the
    absence of cocaine (i.e., during craving).
  • With repeated use of cocaine, the body relies on
    this drug to maintain rewarding feelings.
  •  

92
Physical Action of Cocaine
  • Dopamine is released into the synaptic space. The
    dopamine binds to dopamine receptors and then is
    taken up by uptake pumps back into the terminal.
  • Cocaine binds to the uptake pumps and prevents
    them from transporting dopamine back into the
    neuron terminal.
  • So more dopamine builds up in the synaptic
    space and it is free to activate more dopamine
    receptors.

93
Cocaine
  • Scientists have measured increased dopamine
    levels in the synapses of the reward pathway in
    rats self-administering cocaine.
  • Rats will press a bar to receive injections
    of cocaine directly into the reward pathway, an
    excellent predictor of the addictive potential of
    this drug.
  • If the injection needle is placed near these
    regions (but not in them), the rat will not press
    the bar to receive the cocaine.

94
Amphetamines
  •  
  • 1-phenylpropan-2-amine
  • A very simple molecule, especially troublesome
    because it can be made from readily
    available chemicals that do not even
    need to be imported.
  •  

95
Ecstasy (MDMA)
  • (3-4 methylenedioxy-methamphetamine)
  • chemical structure similar to methamphetamine

96
AmphetaminesEcstasy
  • Ecstasy (MDMA), amphetamines and cocaine are all
    stimulants and cause similar problems. They
    include
  • depression, sleep problems, drug craving, and
    severe anxiety, sweating
  • paranoia during and sometimes weeks after use,
  • psychotic episodes have been reported
  • muscle tension, teeth-clenching,
  • increases in heart rate and blood pressure
  • long-term brain damage

97
Marijuana
  • Marijuana (Delta-9 THC)
  •  
  • There are cannabinoid receptors in the
    human brain, currently a major subject of
    medical research.

98
Marijuana Medical Uses
  • Known medical uses include
  • Appetite stimulation/ anti-weight loss and body
    wasting (cachexia)
  • Nausea and vomiting following cancer chemotherapy
  • Glaucoma
  • Neurological and movement disorders
  • Source NIDA http//www.nida.nih.gov/researchrep
    orts/marijuana/Marijuana3.htmlhippohippo

99
Marijuana Concerns
  • Current research interests include the effects of
    smoked marijuana / extracts of marijuana on
    appetite stimulation, certain types of pain, and
    spasticity due to multiple sclerosis.
  • However, the potential benefits must be weighed
    against the adverse effects of marijuana smoke on
    the respiratory system.
  • Marijuana has over 400 different compounds, for
    most of which little is known about the effects,
    including possible deleterious effects on
    patients with diverse medical conditions.

100
Marijuana Effects
  • Summary of Marijuana Effects
  • Acute (present during intoxication)
  • Impairs short-term memory
  • Impairs attention, judgment, and other cognitive
    functions
  • Impairs coordination and balance
  • Increases heart rate

101
Marijuana Effects
  • Persistent (lasting longer than intoxication, but
    may not be permanent)
  • Impairs memory and learning skills
  • Long-term (cumulative, potentially permanent
    effects of chronic abuse)
  • Can lead to addiction
  • Increases risk of chronic cough, bronchitis, and
    emphysema
  • Increases risk of cancer of the head, neck, and
    lungs

102
Marijuana Risks
  • With heavy, long-term use, THC affects processing
    of information in the hippocampus, leading to
    impaired ability to form memories, recall
    events and shift attention from one thing to
    another.
  • THC also binds to receptors in the cerebellum and
    basal ganglia, disrupting coordination, balance,
    posture, coordination of movement, and reaction
    time.
  • Accidents are associated with marijuana
    intoxication. Approximately 6 to 11 percent of
    fatal accident victims test positive for THC.

103
Marijuana Risks
  • A National Highway Traffic Safety Administration
    found that a moderate dose of marijuana alone
    impaired driving performance. Even a low dose of
    marijuana combined with alcohol led to markedly
    greater impairments than either drug alone.
  • High doses of marijuana, especially when consumed
    in food or drink may create a pharmacological
    psychosis, symptoms of which include
    hallucinations, delusions, and
    depersonalization (loss of the sense of personal
    identity or self-recognition).

104
Hallucinogens
  • Serotonin LSD
  • The structure of LSD is very similar to other
    hallucinogenic drugs such as mescaline and
    psilocybin, (substituted indole ring).
  • LSD also has a serotonin-blocking effect.

105
Hallucinogens
  • Serotonin is a neurotransmitter occurring
    naturally in various organs of warm-blooded
    animals.
  • It plays an important role in the biochemistry
    of psychic functions.
  • LSD also influences functions that are connected
    with dopamine, which is another naturally
    occurring neurotransmitter.
  • Most of the brain centers receptive to dopamine
    become activated by LSD, but some others
    are depressed.

106
Dissociative Agents
  • A dissociative anesthetic causes interruption of
    pathways between the limbic system and cortical
    system causing marked analgesia.
  • Produce a catalepsy-like state, in which the
    patient feels dissociated from the environment.
  • Examples
  • Ketamine
  • Phencyclidine (PCP, Angel Dust)
  • Tiletamine

107
Benzodiazepines (Sedative-Hypnotics)
  • Benzodiazepines are probably the most widely
    taken family of psychotropic drugs in
    history, but they have addictive potential.
  • Examples
  • Xanax, alprazolam 
  • Librium, chlordiazepoxide 
  • Klonopin, clonazepam 
  • Valium, diazepam
  • Rohypnol, flunitrazepam 
  • Ativan, lorazepam

108
Benzodiazepines (Sedative-Hypnotics)
  • Prior to the invention of benzodiazepines, the
    most commonly used drugs for sedation and sleep
    were the barbiturates, which had been invented at
    the dawn of the 20th century.
  • Very toxic and highly addictive barbiturate
    poisoning accounted for a great number of deaths
    every year and abrupt withdrawal could cause
    death.
  • The therapeutic index the difference between an
    effective dose and a poisonous dose was very
    low.
  •  

109
Mechanism of Addiction Summing Up
  • Although each drug may have a different mechanism
    of action, each drug increases the activity of
    the reward pathway by increasing dopamine
    transmission.
  • Persons in recovery from a preferred drug can be
    driven back to its use by other drugs, even if
    they dont particularly like the other drug,
    because all these drugs activate the common brain
    pathway for reward.
  • Addiction is truly a disease of the brain, and as
    scientists learn more, they may find more
    effective treatment for the recovering addict. 

110
Psychiatry and Addiction Medicine
  • A Key Interdisciplinary Interface

111
Dual Diagnosis
  • Definition A person who has both an alcohol or
    drug problem and a psychiatric problem is said to
    have a dual diagnosis.  To recover fully, the
    person needs treatment for both problems.
  • Prevalence According to the Journal of the
    American Medical Association (JAMA), thirty-seven
    percent of alcohol abusers and fifty-three
    percent of drug abusers also have at least one
    serious mental illness. Also, of all people
    diagnosed as mentally ill, 29 percent abuse
    either alcohol or drugs.

112
Psychiatric Problems Commonly Associated with
Increased Risk of Substance Use Disorders
  • The following table is based on a National
    Institute of Mental Health study, lists seven
    major psychiatric disorders and shows how much
    each one increases an individuals risk for
    substance abuse.
  • Personality disorder -15.5
  • Manic episode - 14.5
  • Schizophrenia -10.1
  • Panic disorder - 4.3
  • Major depressive episode - 4.1
  • Obsessive-compulsive disorder - 3.4
  • Phobias - 2.4

113
Which is the Primary Disorder Substance Use or
the Psychiatric problem?
  • Often, the psychiatric problem came first. 
  • Substance use in the attempt to feel calmer, more
    energetic, or more cheerful, a person with
    emotional symptoms may drink or use drugs
    (self-medication.) 
  • Frequent self-medication may eventually lead to
    physical or psychological addiction to alcohol or
    drugs, so the person then suffers from not just
    one problem, but two. 
  • In adolescents, however, drug or alcohol abuse
    may merge and continue into adulthood, which may
    contribute to the development of emotional
    difficulties or psychiatric disorders.

114
When the Substance Use Disorder is Primary
  • Substance abuse problems may cause signs and
    symptoms that mimic other psychiatric conditions,
    such as depression, fits of rage, hallucinations,
    or suicide attempts, making the distinction
    difficult.
  • Medically supervised withdrawal from alcohol
    and/or drugs may be necessary before the doctor
    can accurately assess whether there is also an
    underlying psychiatric problem.
  • If a person does have both an alcohol/drug
    problem and an emotional problem, both problems
    should be treated simultaneously. 
  • However, the first step in treatment may have to
    be detoxification / stabilization.

115
Scott C.L., Lewis C.F., McDermott B.E. Dual
diagnosis among incarcerated populations
Exception or rule? Journal of Dual Diagnosis.
3(1)(pp 33-58), 2006
  • Objectives Multiple studies indicate that the
    prevalence of mental illness and substance use
    disorders is substantially higher in correctional
    environments when compared with community rates.
  • Methods An extensive electronic literature
    search was conducted through PubMed, Medline,
    Department of Justice, and the National
    Commission on Correctional Health Care.
  • Results The literature reviewed indicated a high
    comorbidity of mental illness and substance use
    disorders in incarcerated individuals.
  • Conclusion Providers who work in correctional
    environments must understand the significant
    prevalence of comorbid mental illness and
    substance use disorders in those incarcerated to
    effectively assess and treat inmates.

116
Maremmani, Icro Pacini, Matteo Perugi,
Giulio Akiskal, Hagop S S Addiction and the
Bipolar Spectrum Dual Diagnosis With a Common
Substrate? Addictive Disorders Their Treatment.
3(4)156-164, December 2004.
  • Drug addiction has been correctly assigned to the
    field of mental illness, due to the nature of its
    symptoms, clinical picture, and its
    pathophysiological pathways within the central
    nervous system.
  • Some similarities have emerged between addictive
    symptoms and psychiatric diseases such as
    hypomania and impulse control disorders,
    including borderline and antisocial personality
    disorders (for all of which we envisage a common
    genetic diathesis).

117
Maremmani, Icro Pacini, Matteo Perugi, Giulio
Akiskal, Hagop S S Addiction and the Bipolar
Spectrum Dual Diagnosis With a Common Substrate?
Addictive Disorders Their Treatment.
3(4)156-164, December 2004.
  • Nevertheless, once established, addiction
    exhibits an autonomous process, and the
    coexistence with other mental disorders
    represents a condition of dual diagnosis.
  • The co-existence with other mental disorders
    shares neurobiological ground on which certain
    psychopathologic dispositions impart an enhanced
    risk of becoming addicted.

118
Maremmani, Icro Pacini, Matteo Perugi, Giulio
Akiskal, Hagop S S Addiction and the Bipolar
Spectrum Dual Diagnosis With a Common Substrate?
Addictive Disorders Their Treatment.
3(4)156-164, December 2004.
  • In particular, we suggest that the bipolar
    spectrum-and its hyperthymic and cyclothymic
    temperamental substrates-is at special risk for
    substance use.
  • In our experience, the contribution of bipolarity
    to the addictive process is often missed
    because subclinical expressions of bipolarity
    along temperamental extremes are insufficiently
    appreciated by both psychiatrists and
    addictionologists.
  • We submit that the present conceptualization of
    the link between addictive and bipolar disorders
    has heuristic clinical and scientific merits.

119
Infectious Disease and Addiction Medicine
  • A Clinically Important Interface to Consider

120
Economics Pressures May Exist Toward Injection
Drug Use
  • Most drugs are very expensive to start with.
  • As addiction progresses and tolerance grows,
    more drugs needed to achieve the same effect, so
    expense increases greatly over time.
  • Drugs administered intravenously are typically
    about twice as potent as drugs ingested, and
    also may have a more rapid onset of action.
  • A person who starts out eating pain pills or
    snorting opiates may face mounting economic
    pressure to begin injecting just to be able to
    afford enough drugs to avoid withdrawal.

121
Relative Contagiousness of Blood-borne
Diseases
  • Per single needle stick
    Hepatitis B (HBV) 6-30 gt
    Hepatitis C (HCV) 3 gt HIV (0.3)
  • However, the amount of blood, freshness of the
    blood, and disease status of patient may increase
    (or decrease) the usual risk of transmission.
  • Contaminated IDU is usually even more readily
    infectious than sex.
  • By Sexual Route
    Hepatitis B gt HIV gt Hepatitis
    C

122
HIV Transmission A General
Overview
  • The most common route of HIV transmission
    worldwide is sex between men and women.
  • In most countries outside Africa, injection drug
    use (IDU) is a major second transmission route.
  • Needle use can cause HIV to spread explosively
    through drug using populations. Part of the
    reason is that IDUs often form very tight groups
    with close social contacts for drug
    distribution.
  • In the Ukraine, the HIV infection rate among
    IDUs increased from 0 in 1994 to an estimated
    31-57 less than two years later.
  • IDUs also remain susceptible to other HIV
    transmission vectors, like unprotected sex.

123
HIV Transmission and Needle Use
  • HIV transmission has been reported with many
    non-opiate injected drugs including
  • cocaine and methamphetamine
  • body building steroids
  • drugs injected for medicinal purposes
    (common practice among migrant farm workers)
  • Needle exchange helps, but needles are not the
    only culprits. Transmission can also occur by
  • contaminated syringes in drug preparation,
    reusing water, bottle caps, spoons, cookers and
    paraphernalia used to heat and dissolve drugs
  • reusing filters of cotton or cigarette filters
    used to filter out particles that might clog the
    needle.

124
HIV Transmission Among Drug Users With Or Without
Needles
  • Sexual risk behavior can occur with or without
    IDU, including
  • sex for drug exchanges
  • sex for money to buy drugs
  • sex with other people who have HIV risk factors
    as a result of the existing pattern of
    social networks among drug users
  • Impaired judgment due to the use of any
    mind-altering substance (including alcohol and
    marijuana) can lead to sexual risk behavior.

125
HIV and Race or Ethnicity (CDC)
  • Cumulative estimated of AIDS cases, through
    2006 (Includes persons with a diagnosis of AIDS
    from the beginning of the epidemic through 2006)
  • White, not Hispanic.394,024
  • Black, not Hispanic..409,982
  • Hispanic.......161,505
  • Asian/Pacific Islander...7,951
  • American Indian/Alaska Native3,345

126
By Transmission Category - Estimated Number
of AIDS Cases, Through 2006
  • Adult and Adult and Total
  • Adolescent Adolescent


    Male Female
  • MSM 465,965 -
    465,965
  • IDU 170,171 74,718
    244,889
  • MSM and IDU 68,516 -
    68,516
  • Heterosexual 65,241 108,252 173,493
  • Other 13,893 6,596
    20,489

127
Hepatitis C Overview
  • Hepatitis C Virus (HCV), formerly called non-A
    non-B hepatitis, infects about 170 million people
    worldwide, about four times as many as HIV.
  • New HCV infections in the U.S. have dropped
    sharply to about 25,000/ year since a test to
    screen donated blood for HCV was approved in
    1990, but many people were infected before the
    blood test was used and have yet to develop
    symptoms.
  • In the early half of this decade, 8,000 to 10,000
    died annually in the United States from HCV.
  • Low percentage of liver cancer in North America,
    but the rate is rising due to HCV.

128
Pathways of
Hepatitis C Infection
  • Spread by contact with the blood of infected
    individuals, primarily through IDU.
  • Health care workers, mostly through needle
    sticks.
  • Straws to snort cocaine or other drugs may be
    invisibly blood-contaminated and spread HCV.
  • Blood transfusions before 1990-1992 when testing
    was developed and commercially available spread
    HCV.
  • Is HCV transmitted in tattoo parlors? Jailhouse
    tattooing? Many conflicting opinions exist. Some
    say the needles or ink can be contaminated.
  • Effective vaccines exist for Hepatitis A and B,
    but unfortunately none exists for C.

129
HCV Spread and Serotypes
  • Appears less contagious than HIV sexually.
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