Download heroin - UNM Biology

HEROIN
“It’s not hypnotic and theirs no
danger in acquiring a habit!”
–Boston Medical and Surgical
Journal 1900
Nick Atencio
&
Gabrielle Sanchez
Introduction
Heroin is a narcotic analgesic derived from morphine.
It is believed to be one of the most addictive drugs
in the world today. For our group this topic was
selected due to interest sparked by friends and
family who have used and died from heroin as well
as coming from a city and state that leads the
nation in heroin related deaths per capita.
This presentation will cover topics such as the history,
routes of administration, mechanism of action,
treatments, effects on babies and laws attributed to
heroin.
“Need Something New”
In the late 1800’s morphine and codeine were the
most popular prescribed and addictive drugs.
The Bayer company in Germany was looking for
alternate medications that were capable of
treating the same diseases as codeine and
morphine (which is derived from the opium
poppy) but yet less potent and less addictive
(Hodgson).
Diacetlymorphine
In 1874, English chemist C.R. Wright ventured out into
making a non-addictive form of codeine and
morphine. In doing so he combined anhydrous
morphine alkoid and acetic andhydride (Hodgson).
This produced what is known as diacetylmorhpine
(Hodgson). In short diacetylmorphine is an
acetylated version of morphine.
Diacetlymorphine
Morphine
Acetylation
“Heroic”
In 1898, Heinrich Dreser of Germany saw the
commercial value in Wright’s invention and
began testing on rabbits, himself and fellow coworkers at the drug company he worked at in
Germany, Bayer (Hodgson). Dreser later then
termed Wright’s invention as “Heroin.” This was
due to the results from testing his co-workers
which said they had a “heroic” like feeling while
using the drug (Hodgson).
“It’s not hypnotic and theirs no
danger in acquiring a habit!”
–Boston Medical and Surgical Journal 1900
In 1898, Dreser advertised Heroin to the Congress
of German Naturalists and Physicians (Hodgson).
Claiming it was 10x more effective then codeine
as a cough medicine with only 1/10 of it’s effects
(Hodgson). Also that it was more effective then
morphine as a pain killer (Hodgson). In 1899,
the Bayer company began advertising heroin to
doctors and practitioners in Europe and the U.S.
(Hodgson).
Routes of Administration
Intravenously a.k.a. Shooting up!
The most common route of administration. Requires user to
dissolve the heroin powder in an acid such as citric acid or
lemon juice in order to break down the heroin (Hart).
Sometimes water. Then heated into fine liquid and injected
intravenously. This route requires smaller doses yet achieves
faster effects then other routes of administration. Most
injections occur on majors veins (aka mainling) such as those
in the arm (Hart). If veins collapse then injections typically will
occur in groin, neck and legs (Hart). Intravenous avoids first
pass metabolism and therefore readily able to cross the blood
brain barrier and effects felt immediately after injection
(Meyer).
Routes of Administration
The second most common route is smoking. Smoking
heroin requires the user to heat the drug in order to
inhale the vapors. Typically heated on tin foil or lacing
the drug with marijuana or tobacco and smoking it in a
pipe or cigarette (Meyer). When heated it turns into a
thick liquid. Smoking heroin is also termed as “chasing
the dragon,” since the user chases the globs of heroin
that are in the tube with the intention of inhaling as
much smoke as possible (Meyer).
Routes of Administration
Snorting heroin is one of the least common
routes. When snorted, users will use a glass
tube or tin foil to make a tube Meyer. Any
residue left in the tin foil tube allows for
further usage. By snorting users bypasses
first pass metabolism in the liver (Meyer).
Routes of Administration
The less common route of administration is
oral intake. When taken orally, heroin
merely serves as a pro-drug for morphine
(Hart). Heroin must first pass metabolism in
the liver when taken orally. It is in the liver
that heroin is converted into morphine
(Meyer).
Distribution
-
-
The acetyl groups in heroin make it more
lipid soluble and able to penetrate the BBB
(Meyer). It is in the brain where heroin is
able to have its overall effects.
Heroin primarily modifies the action of
dopamine in the nucleus accumbens and
ventral tegemental area (VTA) of the brain
(Meyer).
Metabolism of Heroin
-Once
crossing the BBB heroin is deacetlyated
into 6-monoacetlylatedmorphine (6-MAM) and
morphine (Hart).
Morphine
Heroin
6-MAM
Mechanism of Action
-
-
-
-
6-MAM and Morphine then act as agonists and bind
to mu, kappa (both play a role in pain reception)
and delta opioid receptors in the brain (Hart).
It is important to note that the mu receptor has the
highest affinity of the three for morphine and opiate
related drugs (Meyer).
This binding then prevents the release of GABA,
therefore reducing the inhibitory effects of GABA on
dopamine neurons (Meyer).
The increase in activation of the dopamine neurons
further results in activation of the post-synaptic
membrane (Meyer). Which then results in the
activation of the dopaminergic reward pathway.
Leading to heroin’s desired effects (Meyer).
(Image from CNSForum)
This is all made possible due to the three opioid
receptors being linked to G proteins. First G protein
activation opens K+ channels which increase K+
exiting the cell (Meyer). This leads to
hyperpolarization of the cell. When the receptors
are on the cell, the hyperpolarization decreases the
cell’s firing rate of GABA (Meyer).
Second opiates such as heroin can have inhibitory
effects by closing Ca2+ channels, when G protein
receptors are on the presynaptic terminal (Meyer).
Reducing Ca2+ intake during an action potential
proportionately decreases the amount of inhibitory
neurotransmitter released (i.e. GABA) (Meyer).
Therefore increasing the amount of dopamine
production and pleasure felt (Meyer).
Mechanism of Action for
Pain Inhibition
Once heroin crosses the BBB and becomes morphine, morphine
is then able to bind to the opiate receptors that trigger
inhibitory spinal neurons to release endorphins (Meyer). It is
these endorphins that then inhibit the spinal projection
neurons from being activated. There are three ways of
inhibiting spinal cord pain transmission (Meyer):
1)
Directly inhibiting the projection neuron.
2) Inhibiting the excitatory neuron
3) Exciting the inhibitory opioid neuron, which sends out a
neuron of its own when activated to inhibit the activation of
the projection neuron.
1) Direct Inhibition of
Projection Neuron
Endorphin
2) Inhibition of
excitatory neuron
Projection Neuron
Endorphin
Projection
Neuron
Excitatory
Interneuron
3) Excitation of inhibitory
opioid interneuron
Opiod Neuron
Projection Neuron
It’s just not worth it!

-
Desired Effects
Euphoria rush
Decrease in anxiety
Reduction in pain

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-
Undesired/Long term effects
Hypothermia
Nausea/vomiting
Bone and muscle pain
Veins collapsing
Lung infections
Increase chances for stroke
Liver/kidney disease
Pulmonary complications
HIV/AIDS
Hepatitis
(Hart)
Excretion


The excretion of heroin occurs a
majority of the time through the
kidneys and out as urine (Hart).
Depending on the amount
administered/frequency heroin levels
in the body vary, therefore complete
excretion from the body varies from
days, to weeks to months.
Overdosing
In the events of a heroin overdose, medical
professionals and in some cases law enforcement
administer naloxone, commonly reffered to as
Narcan.
Narcan acts as an antagonist and reverses the
traumatic effects of a heroin overdose by
competing with morphine for the opiate receptors
(mostly the mu receptors) and binding to them
therefore reversing the effects of heroin overdosing
such as respiratory depression and sedation
(Meyer).
It is administered via I.V., I.M. or S.C. (sub
cutaneously) and is excreted through the urine
within 72 hours (A.P.A) .
One down fall to the usage of Narcan is the onset of
withdrawal symptoms for the heroin user.
Withdrawal
The onset of withdrawal symptoms vary
among users. Typically those who use
heroin once a day experience peak
withdrawal effects within 36-48 hours of
there last administered dose (A.P.A).
Symptoms such as pain, restlessness and
vomiting go away within in 7-10 days
(Meyer).
There are several treatments for withdrawal,
methadone is one of them.
Methadone
Methadone helps alleviate withdrawal
symptoms. When taken orally it occupies
opiate receptors (like heroin) (Meyer). In a
sense it acts like heroin by reducing the
need for more heroin, therefore causing a
reduction in withdrawal side effects (Meyer).
It is important to note that Methadone does
not provide any of the euphoric effects that
heroin does when administered.
Narcan vs Methadone
When coming off of heroin it is best to quit
“cold turkey” and seek prescribed
methadone treatment. When Narcan is used
opiate receptors are more rapidly deprived
of opiate compared to quitting “cold turkey”
(Hart).
However, one complication with methadone is
that some individuals will begin to become
addicted to methadone if it is not prescribed
in adequate amounts (Meyer).
Heroin Use During
Pregnancy


Heroin is easily made available to the unborn baby
because it can cross the placenta and enter the
blood stream of the baby. Most of the blood
supplied to babies does not experience the first
pass effect, it does not pass through the mother’s
liver, and thus is more potent (Blackburn).
Heroin once broken into its metabolites becomes
less lipid soluble and stays trapped on the fetal side
of the placenta (Blackburn). There it begins to
accumulate in the fetus and the amniotic fluid.
(Blackburn)
(Merck)
The affects of Heroin on
Babies

Heroin can cause
serious complications
during pregnancy
including miscarriage,
premature birth,
decreased weight, birth
defects, withdrawal
symptoms (or Neonatal
Abstinence Syndrome),
behavioral or learning
disabilities, and are at a
larger risk for sudden
infant death syndrome
(SIDS). (March of
Dimes)
•Babies that experience
withdrawals show symptoms
including fever, sneezing,
trembling, irritability, vomiting,
diarrhea, and sometimes
seizures. (Edwards)
Treatment for Mothers

Mothers who are using are encouraged to
seek treatment from professional medical
staff. Treatments such as methadone or
minimal amounts of opiates for the baby in
order to prevent withdrawal symptoms at
birth (Edwards). Where as completely
quitting heroin, A sudden decrease of
heroin may have serious negative affects on
the baby ranging from breathing
complications to seizures (Edwards).
Heroin by the Numbers
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The average heroin addict will spend $150 to $200
dollars a day to support their habit (G.D.C.A.D.A).
It is estimated that there were 149,000 new heroin
users in 1998 with nearly 80% under the age of 26.
(G.D.C.A.D.A).
Current estimates suggest that nearly 600,000
people in America need treatment for heroin
addiction. (Heroin Addiction)
In the 25 to 49 age group, illicit drug overdose is
the fourth leading cause of death, about the same
number as motor vehicle crashes. (Heroin
Addiction)
Heroin Studies and
Classification



One study recently conducted found that addicts
will find themselves overdosing on there normal
dose of heroin if administered in a new
environment. For more information on this study
visit:
http://www.pubmedcentral.nih.gov/articlerender.fcg
i?artid=1196296
Heroin is a Schedule I drug, labeling it as one of
the most easily addictive drugs (A.P.A.).
Animals can also become just as addicted as
humans, 3 elephants were rescued from smugglers
who were lacing their bananas with the drug
heroin. The elephants are easily irritated and
cannot return to the wild. (Telegraph.co)
Heroin Laws




Due to the increase in heroin use in the early 1900’s, congress
passed the Harrison Act of 1924. Which made it illegal to
produce, import or distribute opiates of any kind. Doctors
however were allowed to prescribe them for medical issues
and not addictive issues (Hodgson).
In New Mexico if heroin is in your possession it is considered a
4th degree felony. If found selling the drug it is considered a
2nd degree felony. However, if the selling of the drug is near a
drug free school zone or is a subsequent offense it is then a
1st degree felony (JRank)
Most national laws include a felony offense with some jail time
included. Punishments depend on the severity of heroin as a
problem in the state.
Monetary values are placed as high as 1 million dollars and jail
time up to life in prison with no parole (JRank).
Not All Exposure is Great
In 1999, Rio Arriba County in New Mexico led the
nation in heroin related deaths per capita (NDIC).
To combat the amount of overdoses/deaths, the
Espanola Police Department required its officers to
start caring Narcan with them at all times (NDIC).
In addition the New Mexico Health Department began
the free needle exchange and Narcan distribution
for heroin users (NDIC).
Recently in April 2008, the New York Times featured
an article/documentry regarding Rio Arriba County
and its small towns struggling with heroin abuse. To
read the article and view the video documentary
visit:
http://www.nytimes.com/2008/04/02/us/02overdose.
html?ref=us&pagewanted=all
Summary
The take home message from this presentation for the audience is three
things.
1)
2)
3)
Heroin is highly addictive which can lead to serious health issues
that may even result in death.
The overdosing and withdrawal side effects/issues presented are
the hardest part for heroin addicts and that treatment for
addiction is a slow and long process that must be monitored by
professionals in the medical field.
Although laws are continually made and enforced, Heroin
continues to be one of the major pandemics of crime and drug
abuse not only across the world and in America but right here in
New Mexico, which is unfortunate for a state that is known as
“The Land of Enchantment.”
If you know someone that is struggling with heroin addiction or would
like more information visit Heroin Help at http://heroinhelp.com/
or call at 1.866.925.4033.
References
American Pharmacists Association. The Pharmacy Technician. p.40-43 Englewood. 2007.
Blackburn, Susan. Maternal, Fetal, and Neonatal Physiology: A Clinical Perspective. p.204-206
Philadelphia, 2007.
"Drug Addiction and Your Baby." Suite101.com: Online Magazine and Writers'
Network. 2007. 22 Apr. 2009 <http://www.suite101.com/article.cfm/maternal_fetal/104588>.
Foley, Michael. “Drug Use During Pregnancy.” Merck. May 2007. 14 Apr. 2009.
http://www.merck.com/mmhe/sec22/ch259/ch259a.html
Hart, Carl. “Drugs, Society and Human Behavior 12th Edition” p.309-328
Boston, MA. McGraw Hill 2008.
“Heroin Elephant Can Never be Freed.” Telegraph.co. 2006. 26 Apr. 2009
<www.telegraph.co.uk/news/worldnews/asia/china>
“Heroin-Facts and Statistics.” Greater Dallas Council on Alcohol and Drug Abuse.2004. 22
Apr. 2009 <www.gdcada.org/statistics/heroin.htm>
“Heroin Laws- Information on the law about Heroin.” JRank. 2007. 26 Apr. 2009
<http:/law.jrank.org/pages/11810/Heroin.html>
“Heroin Statistics.” Heroin Addiction 2. 2005. 22 Apr. 2009
www.heroinaddiction2.com.heroin-statistics.htm
Hodgson, Barbar. “How Aspirin Turned Hero.” 1999
http://www.heroin-addiction.info/history.htm
“Illicit Drug Use During Pregnancy.” March of Dimes Foundation. 22 Apr. 2009
http://www.marchofdimes.com/professionals/14332-1169.asp.
Meyer, Jarold. “Psychopharmacology: Drugs, The Brain and Behavior.” p.247-269
Sunderland, MA. Sinauer Assoc. Inc. 2005.
“New Mexico Drug Threat Assessment.” NDIC. April 2002. 27 Mar. 2009.
http://www.usdoj.gov/ndic/pubs07/803/heroin.htm
“The mechanism of action of heroin at the mu (m) opiate receptors.” CNSForum. 2005. 14 Apr. 2009
http://www.cnsforum.com/imagebank/item/moa_heroin_mu/default.aspx