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Understanding Substance Use Disorders. Jean J. Bonhomme M.D., M.P.H. Assistant Professor, Morehouse School of Medicine Department of Psychiatry [email protected] Role of the Pediatrician. Most substance use disorders actually begin in the pediatric age group.

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Understanding substance use disorders

Understanding Substance Use Disorders

Jean J. Bonhomme M.D., M.P.H.

Assistant Professor, Morehouse School of Medicine

Department of Psychiatry

[email protected]


Role of the pediatrician
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.


The cdc s best practices for comprehensive tobacco control programs 1999
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)


Morehouse school of medicine
Morehouse School of Medicine Programs (1999)

  • Morehouse Presidents David Satcher, Louis Sullivan, and James Gavin (2004):

  • Tobacco companies actively target minority youth using:

    • Tobacco ads and products placed at children’s eye level in retail outlets

    • Fruit flavored tobacco products

    • Hip-hop packaging


Cultural factors impacting this group
Cultural factors impacting this group Programs (1999)

  • 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.


Morehouse presidents
Morehouse Presidents Programs (1999)

  • 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.


Signs of drug use by children
Signs of Drug use by Children Programs (1999)

  • 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


Signs of drug use by children1
Signs of Drug use by Children Programs (1999)

  • 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


Addiction vs dependence an important new distinction

Addiction vs. Dependence: an important new distinction

Source: Principles of Addiction Medicine, 3rd Edition American Society of Addiction Medicine


Addiction defined
Addiction Defined new distinction

  • 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.


Dependence defined
Dependence Defined new distinction

  • 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.


What is the importance of this distinction
What is the Importance of This Distinction? new 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.



Brain areas in addiction prefrontal cortex
Brain Areas In Addiction: new distinctionPrefrontal Cortex


Brain areas in dependence brainstem and thalamus
Brain Areas In Dependence: new distinctionBrainstem and Thalamus


The anatomy underlying this distinction
The Anatomy Underlying new distinctionThis 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.


Dependence explained
Dependence Explained new distinction

  • 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.


Dependence explained1
Dependence Explained new distinction

  • 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.


Why did dsm iv fail to make this distinction
Why Did DSM-IV Fail to Make This Distinction? new 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.


So how do we define substance abuse
So How Do We Define Substance new distinctionAbuse?

  • 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 “That’s it – I’m through with this stuff.”

  • This is not addiction, because they voluntarily left it alone when it clearly became more trouble than it’s worth.

  • A true addict cannot do this.


Tolerance explained
Tolerance Explained new distinction

  • 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.


Mechanisms of tolerance
Mechanisms of Tolerance new distinction

  • 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.


The withdrawal syndrome explained
The Withdrawal Syndrome Explained new distinction

  • 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.


The withdrawal syndrome does not equal addiction
The Withdrawal Syndrome Does NOT Equal Addiction new distinction

  • 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.



Route of drug administration and risk of addiction
Route of Drug Administration and Risk of Addiction new distinction

  • 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.


Example cocaine
Example: Cocaine new distinction

  • 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.


Route of administration and addiction potential
Route of Administration and Addiction Potential new distinction

  • 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.


Example cocaine1
Example: Cocaine new distinction

  • 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.


Route of administration and addiction potential1
Route of Administration and Addiction Potential new distinction

  • 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.


Route of administration and addiction potential2
Route of Administration and Addiction Potential new distinction

  • 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.


Route of administration and needle aversion
Route of Administration and Needle Aversion new distinction

  • 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.


Pharmacological half life and addiction
Pharmacological Half-Life and Addiction new distinction

  • 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.


Pharmacological half life and addiction1
Pharmacological Half-Life and Addiction new distinction

  • 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.


Neurotransmitters 101

Neurotransmitters 101 new distinction

The Basics


Why discuss neurotransmitters
Why Discuss Neurotransmitters? new distinction

  • 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


Key neurotransmitter functions
Key Neurotransmitter Functions new distinction

  • Acetylcholine (Ach): thought, movement

  • Dopamine (DA): pleasure, motion

  • Serotonin: relaxation, mood

  • Glutamate: the brain’s accelerator pedal

  • Gamma-amino-butryic acid (GABA): the brain’s brake pedal

  • Endorphins (Enkephalins, Dynorphins): the brain’s natural painkillers


So with neurotransmitters how does addiction work
So With Neurotransmitters, How Does Addiction Work? new distinction

  • By altering neurotransmitter actions, sometimes in complex ways, addictive drugs hijack the brain’s 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.


Demographics

Demographics new distinction

Who Is Using All These Drugs?


The demographics of substance use disorders
The Demographics of Substance Use Disorders new distinction

  • 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.


Alcohol vs drugs
Alcohol vs. Drugs new distinction

  • In 2004, about 22.5 million Americans aged > 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.)


Cocaine hallucinogens mdma and marijuana use
Cocaine, Hallucinogens, MDMA and Marijuana Use new distinction

  • 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).


Nonmedical use of psychotherapeutic medications
Nonmedical Use of Psychotherapeutic Medications new distinction

  • 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.


Employment status and drug use
Employment Status and Drug Use new distinction

  • 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.”


Ethnicity and drug use dispelling the myths
Ethnicity and Drug Use: Dispelling the Myths new distinction

  • In 2004, 7.9% of the population aged 12–17 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.


Mortality and morbidity of untreated opiate addiction
Mortality and Morbidity of Untreated Opiate Addiction new distinction

  • 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.


The economic costs of heroin addiction in the united states
The economic costs of heroin addiction in the United States new distinction

  • 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.


Is the problem of opiate addiction likely to increase
Is the Problem of Opiate Addiction Likely to Increase? new distinction

  • 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.


Drugs and the law

Drugs and the Law new distinction


Ethnicity and differential sentencing for drug possession
Ethnicity and Differential Sentencing for Drug Possession new distinction

  • 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.


Is a sentencing differential of this magnitude rational or justifiable
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.


According to u s district judge clyde s cahill of missouri
According to U.S. District Judge Clyde S. Cahill of Missouri Justifiable?

  • 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.


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.


Mumola, C., & Beck, A. (1997). 13). 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.


Federal sentencing
Federal Sentencing 13).

  • 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.


Drug properties

Drug Properties 13).

Part I: Drugs Not Commonly Thought of as Drugs


Nicotine
Nicotine 13).

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

Nicotine


Nicotine1
Nicotine 13).

  • 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.


Nicotine2
Nicotine 13).

  • 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.


Nicotine3
Nicotine 13).

  • Stimulation of cholinergic neuronsby nicotine also promotes the release of the neurotransmitter dopamine in the brain’s reward pathways as well.

    • brings on pleasant, happy feelings

    • encourages repeating the nicotine- seeking actions again and again.


Nicotine4
Nicotine 13).

  • 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.


Nicotine5
Nicotine 13).

  • 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.


Alcohol kinetics behavior in the body
Alcohol Kinetics 13). (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:


Alcohol
Alcohol 13).

  • 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


Alcohol1
Alcohol 13).

  • 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.


Key points in the metabolism of alcohol
Key Points in the Metabolism of Alcohol 13).

Alcohol to Acetaldehyde to Acetic Acid


Alcohol metabolism
Alcohol 13). 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.


Alcohol metabolism1
Alcohol 13). 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.


Alcohol metabolism2
Alcohol 13). 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


Racial genetic variation in alcohol metabolizing enzymes
Racial Genetic Variation in Alcohol Metabolizing Enzymes 13).

  • 50% of Asian populations (including Chinese, Japanese, Taiwanese, Korean) have a variation in Aldehyde DeHydrogenase (called ALDH2*2) 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 ALDH2*2 allele.


Alcohol behaves somewhat differently in the genders
Alcohol Behaves Somewhat Differently in the Genders 13).

  • 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 woman’s blood alcohol levels would come out to be higher than the man’s.

  • Women can be alcoholic and suffer liver damage at what would be considered a moderate consumption level for a man.


Alcohol behaves somewhat differently in the genders1
Alcohol Behaves Somewhat Differently in the Genders 13).

  • 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.


Alcohol drug effects
Alcohol Drug Effects 13).

  • 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.


Blood alcohol concentration bac
Blood Alcohol Concentration (BAC) 13).

  • 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


Blood Alcohol Concentration (BAC) 13).

  • 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).


Blood alcohol concentration bac1
Blood Alcohol Concentration (BAC) 13).

  • 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.


Blood alcohol concentration bac2
Blood Alcohol Concentration (BAC) 13).

  • 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).


Alcohol and behavior reinforcement
Alcohol and Behavior Reinforcement 13).

  • 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 brain’s reward system.


Alcohol and genetics
Alcohol and Genetics 13).

  • 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.


Mechanism of alcohol action in the reward system
Mechanism of Alcohol Action in the Reward System 13).

  • 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.


Alcohol and the dopamine and opioid systems
Alcohol and the Dopamine and Opioid Systems 13).

  • 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.


More on the drug therapy of alcoholism
More On the Drug Therapy of Alcoholism 13).

  • 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).


Drug properties1

Drug Properties 13).

Part II: Commonly Recognized Drugs


Opiates
Opiates 13).

  • Opioids have morphine-like actions.

  • Natural opiates are alkaloids found in the resin of the opium poppy e.g.: morphine, codeine and thebaine.

  • Semi-syntheticopiates are chemically altered derivatives of natural opioids, e.g.:

    • hydromorphone,

    • hydrocodone,

    • oxycodone,

    • oxymorphone,

    • diacetylmorphine (heroin)


Opiates1
Opiates 13).

  • Fully synthetic opioids are artificial compounds with opioid activity, e.g.:

    • fentanyl,

    • methadone,

    • tramadol (ultram), and

    • propoxyphene (darvon).


Opiates2
Opiates 13).

  • Endogenous opioid peptides are substances produced naturally by the body,e.g.: endorphins, enkephalins, and dynorphins.

  • Morphine is “Endorphin’s evil twin”


Opiates3
Opiates 13).

  • 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.


Opiates4
Opiates 13).

  • 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).


Opiates5
Opiates 13).

  • 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.


Cocaine
Cocaine 13).

  • 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.


Cocaine addiction and reward pathway activation
Cocaine Addiction and Reward Pathway Activation

  • Cocaine binding in another area, the caudate nucleus (which affects movement and is affected in Parkinson’s 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.


Physical action of cocaine
Physical Action of Cocaine Reward Pathway Activation

  • 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.


Cocaine1
Cocaine Reward Pathway Activation

  • 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.


Amphetamines
Amphetamines Reward Pathway Activation

  • 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.


Ecstasy mdma
Ecstasy (MDMA) Reward Pathway Activation

  • (3-4 methylenedioxy-methamphetamine)

  • chemical structure similar to methamphetamine


Amphetamines ecstasy
Amphetamines Reward Pathway ActivationEcstasy

  • 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


Marijuana
Marijuana Reward Pathway Activation

  • Marijuana (Delta-9 THC)

  • There are cannabinoid receptors in the human brain, currently a major subject of medical research.


Marijuana medical uses
Marijuana Medical Uses Reward Pathway Activation

  • 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/researchreports/marijuana/Marijuana3.html#hippo#hippo


Marijuana concerns
Marijuana Concerns Reward Pathway Activation

  • 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.


Marijuana effects
Marijuana Effects Reward Pathway Activation

  • 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


Marijuana effects1
Marijuana Effects Reward Pathway Activation

  • 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


Marijuana risks
Marijuana Risks Reward Pathway Activation

  • 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.


Marijuana risks1
Marijuana Risks Reward Pathway Activation

  • 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).


Hallucinogens
Hallucinogens Reward Pathway Activation

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.


Hallucinogens1
Hallucinogens Reward Pathway Activation

  • 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.


Dissociative agents
Dissociative Agents Reward Pathway Activation

  • 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


Benzodiazepines sedative hypnotics
Benzodiazepines (Sedative-Hypnotics) Reward Pathway Activation

  • 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


Benzodiazepines sedative hypnotics1
Benzodiazepines (Sedative-Hypnotics) Reward Pathway Activation

  • 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.


Mechanism of addiction summing up
Mechanism of Addiction: Summing Up Reward Pathway Activation

  • 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 don’t 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. 


Psychiatry and addiction medicine

Psychiatry and Reward Pathway ActivationAddiction Medicine

A Key Interdisciplinary Interface


Dual diagnosis
Dual Diagnosis Reward Pathway Activation

  • 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.


Psychiatric problems commonly associated with increased risk of substance use disorders
Psychiatric Problems Commonly Associated with Reward Pathway ActivationIncreased 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 individual’s 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%


Which is the primary disorder substance use or the psychiatric problem
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.


When the substance use disorder is primary
When the Substance Use Disorder is Primary Psychiatric problem?

  • 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.


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.


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).


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.


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.


Infectious disease and addiction medicine

Infectious Disease and Addiction Medicine Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

A Clinically Important Interface to Consider


Economics pressures may exist toward injection drug use
Economics Pressures May Exist Toward Injection Drug Use Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • 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.


Relative contagiousness of blood borne diseases
Relative Contagiousness of Blood-borne Diseases Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • Per single needle stick: Hepatitis B (HBV): 6-30% > Hepatitis C (HCV) 3% > 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 > HIV > Hepatitis C


Hiv transmission a general overview
HIV Transmission: A General Overview Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • 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 IDU’s often form very tight groups with close social contacts for drug distribution.

    • In the Ukraine, the HIV infection rate among IDU’s increased from 0% in 1994 to an estimated 31-57% less than two years later.

  • IDU’s also remain susceptible to other HIV transmission vectors, like unprotected sex.


Hiv transmission and needle use
HIV Transmission and Needle Use Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • 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.


Hiv transmission among drug users with or without needles
HIV Transmission Among Drug Users With Or Without Needles Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • 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.


Hiv and race or ethnicity cdc
HIV and Race or Ethnicity (CDC) Hagop S [S] Addiction and the Bipolar Spectrum: Dual Diagnosis With a Common Substrate? Addictive Disorders & Their Treatment. 3(4):156-164, December 2004

  • 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 Native………3,345


By transmission category estimated number of aids cases through 2006
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


Hepatitis c overview
Hepatitis C Overview Cases, Through 2006

  • 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.


Pathways of hepatitis c infection
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.


Hcv spread and serotypes
HCV Spread and Serotypes Infection

  • Appears less contagious than HIV sexually.

  • Six serotypes are currently known: Type 1 is over 75% of cases in U.S. - the most difficult to treat. Types 2 and 3 respond more easily to therapy.

  • Types 4-6 exist, but mostly outside the US.

  • HCV is more common in the U.S. than HIV or HBV.

    • Estimated 4 million are HCV infected at some point in their lives, with 2.8 million carriers.

    • Hepatitis B - 1.25 million carriers

    • HIV- about 1 million infected

  • HCV is THE most common reason for liver transplantation in the United States.


Demographic determinants of hepatitis c virus seroprevalence among blood donors
Demographic Determinants of Hepatitis C Virus Seroprevalence Among Blood Donors

  • Authors: Murphy, Edward L. MD, MPH; Bryzman, Stephen PA, MPH; Williams, Alan E. PhD; Co-Chien, Harvey MS; Schreiber, George B. DSc; Ownby, Helen E. PhD; Gilcher, Ronald O. MD; Kleinman, Steven H. MD; Matijas, Lauri MS; Thomson, Ruth A. MPH; Nemo, George J. PhD

  • Source: JAMA. 275(13):995-1000, 1996.

  • Objective: To measure demographic factors determining the prevalence of hepatitis C virus (HCV) among blood donors in the United States.


Demographic determinants of hepatitis c virus seroprevalence among blood donors1
Demographic Determinants of Hepatitis C Virus Seroprevalence Among Blood Donors

  • Subjects: A total of 862,398 consecutive volunteer blood donors with one or more donations from March ‘92 through Dec. ‘93.

  • Results: There were 3126 donors with at least one blood donation confirmed HCV-positive, for a crude prevalence of 3.6 per 1000.

  • HCV was most prevalent (6.9 per 1000) in donors aged 30 to 39 yrs.

  • It was only 0.5 per 1000 in donors younger than 20 yrs., and also less in older age groups.


Demographic determinants of hepatitis c virus seroprevalence among blood donors2
Demographic Determinants of Hepatitis C Virus Seroprevalence Among Blood Donors

  • Educational attainment was a factor:

  • 30 to 49-year-olds with less than a high school diploma were at highest risk of HCV infection.

  • Their odds were 33 times higher when compared with those younger than 30 years with a bachelor's degree or higher degree.

  • With HCV seropositivity, odds are over ten times higher for Seropositivity for human T-lymphotropic virus types I and II, HIV, or hepatitis B core antigen.


Demographic determinants of hepatitis c virus seroprevalence among blood donors3
Demographic Determinants of Hepatitis C Virus Seroprevalence Among Blood Donors

  • Other independent risk factors for HCV seropositivity included:

    • Male sex (OR, 1.9)

    • Black race (OR, 1.7)

    • Hispanic ethnicity (OR, 1.3)

    • Previous blood transfusion (OR, 2.8) and

    • First/only time donor status (OR, 4.2 compared with repeat donors).


Biopsy staging of liver disease
Biopsy Staging of Liver Disease Among Blood Donors

  • Determines the extent of damage to the liver caused by viral or non-viral hepatitis.

  • Grades the amount of scarring from 0 to 4.

  • Zero is no scarring, four is cirrhosis

  • Is cirrhosis reversible? Some positive indications.

  • NIH guidelines recommend treatment for any grade 1 or above liver biopsies.

  • Methodology exists for measuring the degree of scarring in the liver through sound waves without needles or tissue samples.


Time of progression to cirrhosis varies with stage of biopsy
Time of Progression to Cirrhosis Varies with Stage of Biopsy Among Blood Donors

  • Stage 4 = cirrhosis Transplant is usually the only option.

  • HCV: from stage 1 to stage 4: median time = 12 years

  • BUT, from stage 3 to stage 4: median time = only 18 months Don’t delay treatment of stage 3 livers!

  • Progression to cirrhosis is accelerated in HIV / HCV co-infected individuals, from 1.5 to 4 times

  • Consider adding one stage to the calculation of stage in HIV / HCV co-infection


Co infection hiv and hcv
Co-Infection: HIV and HCV Among Blood Donors

  • Having HIV and HCV in the same individual at the same time is not at all unusual.

  • HIV and HCV share a common route of infection: Both HIV and HCV are spread by contact with human blood and blood products. 50-90% of people who got HIV through IDU also picked up HCV.

  • Approximately 4 million people test positive for HCV antibody in the U.S., and over 1 million are HIV positive in the U.S.

  • More than 400,000 HIV+ (40%) also have HCV.


Co infection hiv and hcv1
Co-Infection: HIV and HCV Among Blood Donors

  • HIV and HCV influence one another:

    • HIV reduces the body’s ability to fight HCV

    • HIV can speed up the progression to severe liver damage from HCV to less than 10 years unless treated.

    • HIV increases the risk of cirrhosis, liver cancer and liver failure. It is often harder to get rid of Hepatitis C through treatment when HIV is present.


Co infection hiv and hcv2
Co-Infection: HIV and HCV Among Blood Donors

  • The addict’s lifestyle has co-factors that may accelerate HCV disease - alcohol, poor diet, etc.

  • HCV associated liver complications are one of the leading causes of death among HIV+ persons.

  • The liver is critically important for processing many HIV medicines, so liver function must be preserved as much as possible for optimal HIV treatment


Cancer of the liver
Cancer of the Liver Among Blood Donors

  • Called Hepatoma or Hepatocellular Carcinoma

  • 75% of these tumors are found in association with cirrhosis of the liver.

  • Low percentage of cancers in North America, but the rate is rising due to Hepatitis C Virus.

  • In parts of Asia and Africa liver cancer comprises 20-30% of all cancers – these are areas of the world where viral hepatitis is common.

  • Also associated with aflatoxins, poisons found in moldy grains and nuts.


Liver cancer
Liver Cancer Among Blood Donors


Woman with liver cancer
Woman With Liver Cancer Among Blood Donors


Hepatitis b hbv
Hepatitis B (HBV) Among Blood Donors

  • The HBV infection pattern is much like HIV. HBV is transmitted by blood contact with infected blood, semen, or vaginal fluids.

  • In fact, one of the first theories about AIDS was that it was caused by a mutant hepatitis B.

  • The risk groups: IDU sharing needles, syringes, spoons or water to inject drugs and straight or gay men or women having unprotected sex

  • However, HBV is much more infectious than HIV. A single particle of the virus is enough to produce the full clinical disease.


Hepatitis b hbv1
Hepatitis B (HBV) Among Blood Donors

  • Clinical Course: Incubation 4 to 26 weeks.

  • Some people have no symptoms while some become seriously ill with yellow jaundice.

  • The majority feel flu-like: feverish, tired and sick.

  • Very few (<1%) can die.

  • 90% or so heal and clear the virus. By contrast, only 20-30% of hepatitis C patients clear the virus and virtually no patients clear HIV.

  • Up to 10% become carriers, about 1.25 million infected in the U.S., some with chronic hepatitis.


Hepatitis b hiv co infection
Hepatitis B / HIV Co-Infection Among Blood Donors

  • More common that HIV/HCV co-infection, but HBV is less likely to cause chronic infection.

  • The influence of HIV on the course of HBV has not been settled. Early studies did not show accelerated disease, but more recent studies show increased HBV viral loads and greater damage.

  • HBV does not appear to influence HIV course but anti-HIV drugs may be toxic to the liver.

  • Chronic HBV/HIV co-infection may be likely to contribute to end-stage liver disease.


Tuberculosis
Tuberculosis Among Blood Donors

  • One-third of the world’s population is infected with Mycobacterium Tuberculosis, the causative agent of TB.

  • Approximately 8 million people develop active TB every year.

  • The HIV/AIDS pandemic has dramatically increased the incidence of this disease worldwide and in drug treatment populations.

  • Strong association with alcoholism

  • HIV+ persons are very susceptible to infection

  • More difficult to treat TB in the setting of HIV


Tuberculosis1
Tuberculosis Among Blood Donors

  • Recent increases in TB morbidity in the U.S. are concentrated in:

    • Racial and ethnic minorities,

    • foreign-born, and

    • persons with HIV.

  • Treatment regimens for TB has >95% cure rates.

  • However, failure of compliance with anti-tuberculosis medications has resulted in an increasing rate of multiple-drug-resistant tuberculosis that responds poorly to therapy.


Multi drug resistant mdr tuberculosis
Multi-Drug Resistant (MDR)Tuberculosis Among Blood Donors

  • A form of tuberculosis that is resistant to two or more of the main drugs (isoniazid and rifampin) used for the treatment of TB.

  • Extensively drug-resistant TB (XDR TB) is TB resistant to the main drugs and also to a major second class of drugs (fluroquinolones) and at least one of three injectable drugs among second-line drugs.

  • Drug-resistant TB is difficult and costly to treat and can be fatal. Treatment involves drug therapy over many months or years and may require surgery.


Multi drug resistant mdr tuberculosis1
Multi-Drug Resistant (MDR)Tuberculosis Among Blood Donors

  • Despite the longer course of treatment, the cure rate decreases from over 90 percent for nonresistant strains of TB to 50 percent or less.

  • In 2005, the CDC reported that 7.8 percent of tuberculosis cases in the U.S. were resistant to isoniazid, and that 1.2 percent of tuberculosis cases in the U.S. were resistant to both isoniazid and rifampin.

  • Only 27% of primary MDR-TB cases were in U.S. born persons, so 73% were foreign-born.

  • The World Health Organization estimates that up to 50 million persons worldwide may be infected with drug resistant strains of TB.


Multi drug resistant mdr tuberculosis2
Multi-Drug Resistant (MDR)Tuberculosis Among Blood Donors

  • A strain of resistant TB develops when a case of drug-susceptible tuberculosis is improperly or incompletely treated:

    • A physician does not prescribe proper treatment regimens or

    • A patient does not adhere to therapy.  Therapy may be hard to stay on because it usually lasts for months, has a financial cost, and may cause unpleasant side effects.Addicts don’t adhere.

  • Once a strain of MDR TB develops it can be transmitted to others just like a normal drug-susceptible strain. 


Nationwide survey of drug resistant tuberculosis in the united states
Nationwide survey of drug-resistant tuberculosis in the United States

  • A. B. Bloch, G. M. Cauthen, I. M. Onorato, K. G. Dansbury, G. D. Kelly, C. R. Driver and D. E. Snider Jr. Division of Tuberculosis Elimination, National Center for Prevention Services, CDC

  • OBJECTIVE--To determine anti-TB drug resistance patterns, geographic distribution, demographic characteristics, and risk factors of reported TB patients in the United States.


Nationwide survey of drug resistant tuberculosis in the united states1
Nationwide survey of drug-resistant tuberculosis in the United States

  • Resistance to the main drugs, isoniazid and/or rifampin was found in 9.5% of cases whose isolates were tested.

  • Cases were found in 107 counties in 33 states.

  • New York City accounted for 61.4% of the nation's MDR TB cases.

  • The 3-month population-based incidence rate of MDR TB in New York City was 52.4 times that of the rest of the nation (9.559 vs 0.182 cases per million population).


Nationwide survey of drug resistant tuberculosis in the united states2
Nationwide survey of drug-resistant tuberculosis in the United States

  • Compared with the rates in the rest of the nation, the relative risk of Multi-drug resistant tuberculosis MDR TB in New York City was:

  • 39.0 in non-Hispanic whites,

  • 299.3 in Hispanics,

  • 420.9 in Asian/Pacific Islanders, and

  • 701.0 in non-Hispanic Blacks.


Testing for tuberculosis in hiv or unknown hiv status consumers
Testing for Tuberculosis In HIV+ or Unknown HIV Status Consumers

  • Title: Association of Tuberculosis Risk With the Degree of Tuberculin Reaction in HIV-Infected Patients.

  • Authors: Girardi, Enrico MD; Antonucci, Giorgio MD; Ippolito, Giuseppe MD; Raviglione, Mario C. MD; Rapiti, Elisabetta MD, MPH; Di Perri, Giovanni MD; Babudieri, Sergio MD

  • Methods: A prospective study on tuberculosis in HIV-infected patients was conducted in 23 infectious disease units in public hospitals in Italy.


Association of tuberculosis risk with the degree of tuberculin reaction in hiv infected patients
Association of Tuberculosis Risk With the Degree of Tuberculin Reaction in HIV-Infected Patients.

  • Conclusions: Among HIV-infected patients whose immune system is intact enough to respond normally to the test, the degree of response to tuberculin does not appear to reflect the degree of immune suppression and is strongly correlated with the subsequent incidence of tuberculosis.

  • To identify HIV-infected patients who are at an increased risk of tuberculosis and may benefit from preventive therapy, a response to PPD of 5 mm appears to be an appropriate cutoff point.


Local needle effects
Local Needle Effects Tuberculin Reaction in HIV-Infected Patients.

  • Abscess

  • Cellulitis

  • Phlebitis

  • Black Tar Heroin “Mexican Mud”

    • More prevalent on West Coast, Southwest

    • Often the reasons people go to HIV testing facilities in San Francisco is the abscesses.

    • Severe abscesses can occur even with sterile injecting equipment.

    • Botulism has been reported.


Bacterial endocarditis
Bacterial Endocarditis Tuberculin Reaction in HIV-Infected Patients.

  • Infection of the heart lining, valves

  • Often unusual microbes in IVDU: Candida Staph endocarditis is common

  • Endocarditis can also result from dental neglect

  • Long term heart valve damage is possible, which may be severe enough to require open heart surgery for valve replacement

  • Long courses of IV antibiotics needed

  • Special attention to right-sided heart murmurs

  • Cardiology grade stethoscope recommended


Dental decay
Dental Decay Tuberculin Reaction in HIV-Infected Patients.

  • The overwhelming majority of dental decay seen in drug clients stems from factors predating treatment.

  • Some methadone preparations have a high sugar content, which may cause problems.

  • Decreased salivation on methadone may contribute to some problems.

  • Dental problems are NOT minor! There is risk of bacterial endocarditis, especially in those with damaged heart valves (previous endocarditis or other reasons). Pain due to untreated dental conditions may predispose to relapse.


STD Rates Tuberculin Reaction in HIV-Infected Patients.

Title: Prevalence of sexually transmitted infections and associated risk factors among populations of drug abusers.

Authors: Hwang Lu-Yu ; Ross Michael W; Zack Carolyn; Bull Lara; Rickman Kathie; Holleman Marsha.

Source: School of Public Health, University of Texas Health Science Center.

Publication: Clinical Infectious Diseases. 31(4). October, 2000. 920-926.


Std rates
STD Rates Tuberculin Reaction in HIV-Infected Patients.

  • A survey (cross-sectional type) was conducted of sexually transmitted diseases (STDs) and risky behaviors among 407 drug abusers in treatment facilities in 1998.

  • Infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus type 2 (HSV-2), and syphilis were detected by serum antibody testing.

  • Chlamydia and gonorrhea were detected by testing nucleic acid levels in urine.


STD Rates Tuberculin Reaction in HIV-Infected Patients.

  • Percentages of patients testing positive:

    • HSV-2, antibodies 44.4%;

    • HCV, antibodies 35.1%;

    • HBV, antibodies 29.5%;

    • HIV, antibodies 2.7%.

    • Syphilis antibodies 3.4%;

    • Chlamydia nucleic acid, 3.7%;

    • Gonorrhea, nucleic acid, 1.7%.


Std rates1
STD Rates Tuberculin Reaction in HIV-Infected Patients.

  • Out of 407 subjects, approximately 62% had markers for one of the STDs.

  • Statistical analysis (logistic regression) was used to identify demographic / behavioral associations:

    • HIV infection was associated with African American race, use of smokable freebase (crack) cocaine, and STD history.

    • HBV infection was associated with age >30 years, IDU, needle sharing, history of drug abuse treatment, and African American race.


Std rates2
STD Rates Tuberculin Reaction in HIV-Infected Patients.

  • HCV infection was associated with an age >30 years, injecting drugs, and needle sharing.

  • HSV-2 infection was associated with age >30 years, female sex, and African American race.

  • Syphilis was associated with a history of STDs.

  • Conclusion: High prevalences of STDs among drug abusers indicate the need for integration of STD screening and treatment into drug treatment programs.


  • Some points on drug testing
    Some Points on Drug Testing Tuberculin Reaction in HIV-Infected Patients.

    • Urine testing:

      • Most common and widely available

      • Narrow time period of detection for most drugs (Long for chronic marijuana and benzodiazepine use), may not detect sporadic use.

      • Poor quantification of level of use, especially alcohol.

    • Saliva testing:

      • Largely immunological methodologies

      • Not all tests FDA approved at this time

      • Mostly used when urine test impractical

      • Also narrow time period of detection


    Some points on drug testing1
    Some Points on Drug Testing Tuberculin Reaction in HIV-Infected Patients.

    • Serum Testing

      • Gives both presence and current level

      • Time period of detection may be narrow

    • Breath testing

      • Largely for alcohol

    • Hair testing

      • Long period of detection, so less frequent testing needed

      • Gives both presence and level

    • Immunoassays my cross react, false positives GC/MS resolves disputed results


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