Transcript Slide 1

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
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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)
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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
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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
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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
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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
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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 school
Loss 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 Children
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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
Source: Principles of Addiction
Medicine, 3rd Edition
American Society of Addiction
Medicine
Addiction Defined
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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
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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?
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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:
N. Accumbens and VTA
Brain Areas In Addiction:
Prefrontal Cortex
Brain Areas In Dependence:
Brainstem and Thalamus
The Anatomy Underlying
This Distinction
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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
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.
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Dependence Explained
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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?
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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?
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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
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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
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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
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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
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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.
Human Circulatory System:
Through the Heart Twice
Route of Drug Administration
and Risk of Addiction
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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
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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
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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: Cocaine
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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 Potential
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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 Potential
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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
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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
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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 Addiction
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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
The Basics
Why Discuss
Neurotransmitters?
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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
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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?
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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
Who Is Using
All These Drugs?
The Demographics of
Substance Use Disorders
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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
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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
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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
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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
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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
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In 2004, 7.9% of the population aged 12–17
years reported current illicit drug use .
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Breakdown by racial/ethnic group:
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26.0% Native American / Alaskan youths
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12.2% for Biracial or Multiracial youths
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11.1% for White youths,
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10.2% for Latino youths,
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9.3% for African-American youths,
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and 6.0% for Asian youths.
Mortality and Morbidity of
Untreated Opiate Addiction
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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
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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?
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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
Ethnicity and Differential
Sentencing for Drug
Possession
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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?
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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
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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.
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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).
Prisoners in 1996. Washington, DC:
U. S. Department of Justice,
Bureau of Justice Statistics.
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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
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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
Part I: Drugs Not
Commonly Thought
of as Drugs
Nicotine
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Nicotine shows structural similarities
to neurotransmitters, explaining its
addictive properties.
Nicotine
Nicotine
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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.
Nicotine
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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.
Nicotine
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Stimulation of cholinergic neurons by
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 nicotineseeking actions again and again.
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.
Nicotine
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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)
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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
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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
Alcohol
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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
Alcohol to Acetaldehyde to Acetic Acid
Alcohol Metabolism
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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 Metabolism
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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 Metabolism
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Antabuse (Disulfiram) in the treatment of
alcoholism acts by blocking aldehyde
dehydrogenase (ALDH) causing the
accumulation of acetaldehyde, giving
drinking some very aversive symptoms:
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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
 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
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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 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.

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.
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
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).
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.
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).
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
brain’s reward system.
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.
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.
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.

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).
Drug Properties
Part II: Commonly
Recognized Drugs
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)
Opiates
 Fully synthetic opioids are artificial
compounds with opioid activity, e.g.:
 fentanyl,
 methadone,
 tramadol (ultram), and
 propoxyphene (darvon).
Opiates
 Endogenous opioid peptides are substances
produced naturally by the body,e.g.:
endorphins, enkephalins, and dynorphins.
 Morphine is “Endorphin’s evil twin”
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.
Opiates



Opioids bind to opiate receptors
concentrated in specific areas within
the reward pathway (including the
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).
VTA,
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.
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.
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



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.
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.
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.
Ecstasy (MDMA)


(3-4 methylenedioxy-methamphetamine)
chemical structure similar to
methamphetamine
Amphetamines
Ecstasy
 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 (Delta-9 THC)
There are cannabinoid receptors
in the human brain, currently a
major subject of medical research.
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/researchreports/mar
ijuana/Marijuana3.html#hippo#hippo
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.
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
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
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.
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).
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.
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.
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
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
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.
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 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
A Key
Interdisciplinary
Interface
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), thirtyseven percent of alcohol abusers and fiftythree 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

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?

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




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
A Clinically
Important
Interface to
Consider
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.
Relative Contagiousness
of Blood-borne Diseases



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




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 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


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)

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





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 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






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





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



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 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 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 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






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





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




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 HCV

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 HCV



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





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
Woman With Liver Cancer
Hepatitis B (HBV)




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 (HBV)






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




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






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
Tuberculosis



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 antituberculosis medications has resulted in an
increasing rate of multiple-drug-resistant
tuberculosis that responds poorly to therapy.
Multi-Drug Resistant
(MDR)Tuberculosis



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 secondline 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)Tuberculosis




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)Tuberculosis


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 drugsusceptible strain.
Nationwide survey of drugresistant 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 drugresistant 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 drugresistant 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



Title: Association of Tuberculosis Risk With
the Degree of Tuberculin Reaction in HIVInfected 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.


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




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







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




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
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



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

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 Rates


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 Rates
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

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 Testing

Serum Testing



Breath testing


Largely for alcohol
Hair testing



Gives both presence and current level
Time period of detection may be narrow
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