Transcript meth_presentation

Methamphetamine
By:
Laura Schmitt de Lacerda
Laura Landon
Jorge Melchor
What is a toxin?



A poisonous substance produced by a
living organism that can be a plant, virus,
or fungi [1]
Toxins are usually very unstable and are
able to cause disease by interacting with a
biological particle and produce antibodies
Ludwig Bierger was the first to define the
term toxin [2]
Why we chose methamphetamine



Methamphetamine is a highly addictive drug
that is usually used illegaly
Methamphetamine drug abuse can cause
serious damages to health
Use and production in the U.S. Has been
increasing

From 1992-2002 hospital admission due to
meth and amphetamine abuse increased
500% [3]
Why we chose methamphetamine


We wanted to research meth to fully understand
it's underlying issues
We wanted to understand:

The mechanism of action

The mechanism of addiction

The effects it has on the body

The therapeutic uses of methamphetamine and
amphetamines
Why we chose methamphetamine

This is important
because it will help us
in our future careers

We will be able to
identify and help drug
abusers

We will understand
the mechanisms that
cause the issues
What is methamphetamine?

Meth is a stimulant of the central nervous
system

It Is considered a psychostimulant

It is very addictive

The form that is abused is a single isomer or a
mixture

D-methamphetamine is the isomer [4]
What is methamphetamine?

As a drug of abuse it
is taken [5]:

Orally

Dissolved in water or
alcohol

Intranasally

By injection

By smoking

It is approved by the
FDA to treat:

ADHD

Obesity

Narcolepsy
What is Methamphetamine?

The therapeutic drug
is a controlled
substance


Desoxyn is its
commercial name
Its medical use is limited by the side effects is
causes such as cardiovascular problems [6]
Where does methamphetamine
come from?


Meth is a synthesized substance that can be
manufactured in many ways
This diagram shows synthesis of meth from
ephedrine and from 1-phenyl-2-propanone [8]
The history of methamphetamine




Meth was first synthesized from ephedrine in
1891 by Nagayoshi Nagai, in Japan [9,10]
It was first used in WW II in Nazi Germany to
improve pilot performance [9]
The first epidemic of meth abuse started in
Japan after the WW II [3]
In Japan, factory workers used meth to be able
to work long hours
The history of methamphetamine



In the 1950's in the U.S., the use of
amphetamines increased because the FDA
prohibited inhaled methamphetamine use
During this time, medical methamphetamine
was introduced to treat obesity
In the 1960's, abusers starting using meth
intravenously

It is believed this was the first time it was used to
generate feelings of euphoria
The history of methamphetamine



Since the 1970's, meth has been illegal in the
U.S.
Although it is illegal, it's abuse continues to
increase
Meth that is not used for medicinal purposes
comes from the clandestine market [3, 9, 10]
Mechanism of Action

Catecholamine concentration is increased

Dopamine is the main catecholamine that is
increased [11]

Serotonin and norephinephrine levels are also
increased [12]

This results in activation of peripheral alpha and
beta adrenergic receptors

This results in an increase in blood pressure, pulse, and
increases secretion of cortisol [11]
Mechanism of Action


The elevated levels of neurotransmitters lead to
feelings of euphoria and a sensation of well-being
The person becomes more aware, attentive, and has
an increased ability to concentrate
How is meth excreted from the
body?
Renal excretion is the means by which
methamphetamine is excreted from the body.
Excretion of meth is enhanced by urinary acidification,
therefore excretion rate is heavily influenced by
urinary pH, optimum pH being 6-8.
About 90% of meth is entirely eliminated in urine.
When excreted, 20-40% of meth dose is excreted as
unchanged drug, and 5-20% as unchanged
amphetamine. [1][2]
Prevalence of use
Methamphetamine prevalence of use is a big public
health concern in the United States.
Through the use of an online survey of noninstitutionalized adults aged 18-49, national-level
prevalence rates were obtained.
Overall prevalence was estimated to be .27%.
Lifetime use was 8.6%.
Use rates for men were (.32%) and women (.23%).
Prevalence of use
Men had a higher 3-year prevalence rate.
Highest overall meth use age subgroup was 18-25
years old, and non-students had higher use (.85%)
than students (.23%). [3]
Why is meth so dangerous?
Methamphetamine abuse has reached epidemic
proportions throughout the United States,
specifically in rural and semirural areas.
Particular characteristics of meth use create conditions
for a “perfect storm” of medical and social
complications.
Meth can be very dangerous due to the highly
addictive nature of the drug, which causes a state of
euphoria not attained in nature.
Why is meth so dangerous?
Meth is also very dangerous due to the ingredients
used to manufacture it, which can be commonly
available household ingredients according to simple
recipes readily available on the internet.
Life-threatening injuries in the frequent fires and
explosions that result when volatile chemicals are
combined are also very common. [4]
What are meth's adverse health
effects?
Methamphetamine is known to cause several adverse
health effects, both fatal and non-fatal as well as
short-and long term health effects.
Some of the effects include stroke, cardiac arrhythmia,
anxiety, insomnia, paranoia and hallucinations. [5]
Fatal causes are sometimes presented with coma,
shock, elevated body temperature 39-42 degrees C,
and acute renal failure. [6]
What are meth's adverse health
effects?
Other adverse effects, which are non-fatal but
nonetheless dangerous include tissue and blood
vessel destruction, inhibiting body’s ability to repair
itself, acne and sores appear, skin elasticity is lost,
affecting physical appearance, and meth or ‘cotton’
mouth appears, which is characterized by broken,
discolored and rotting teeth caused by the drug’s
effect on salivary glands, which dries them out.
Finally, STD contraction is increased, as meth
heightens sexual drive and impairs judgment, which
can lead to risky sexual behavior [7]
What are meth's adverse health
effects?
Why are higher doses needed for
the same high?
Methamphetamine increases the activity of the
norepinephrine system in the periphery and of the
dopamine system in the central nervous system.
Meth causes the release of these neurotransmitters
and blockade of their reuptake into the presynaptic
nerve terminal.
Meth’s prolonged actions at the synapse cause
depletion of available neurotransmitters for further
release.
Why are higher doses needed for
the same high?
Meth’s actions become less potent after multiple
administrations, an effect referred to as short term
tolerance or tachyphylaxis.
These tolerance mechanisms explain, in part, the need for the
chronic abuser to escalate the quantity of meth per dose
during multiple self-administrations (binges).[8]
Also, prolonged overstimulation of dopamine receptors caused
by methamphetamine may eventually cause the receptors
to down regulate in order to compensate for increased
levels of dopamine within the synaptic cleft. [9]
How is meth taken?
Studies have shown that the subjective pleasure of the
drug use is proportional to the rate at which the
blood level of the drug increases.
These findings suggest the route of administration
used affects the potential risk for psychological
addiction independently of other risk factors, such
as dosage and frequency of use.[10]
Inhalation of methamphetamine
Inhalation of meth refers to inhaling the vaporized
fumes of meth, and not burning it to inhale the
resulting smoke.
Commonly smoked in glass pipes or off of aluminum
foil, which is heated underneath by a flame.
Inhalation is a method which has a relatively high risk
of dependence.
Intravenous injection
Intravenous is the fastest route of drug administration,
causing blood concentrations to rise the most
quickly.
The onset of the rush induced by injection can occur
in as little as a few seconds.
Injection is also the route with the greatest health risk.
Oral ingestion of meth
Oral ingestion does not produce a rush or an acute
transcendent state of euphoria, since oral route
administration requires approximately half an hour
before the high sets in.
Oral route has a low risk for dependence.
How are meth symptoms treated?

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At this time, there are no pharmacological
treatment for meth abusers
The National Institute on Drug Abuse (NIDA) is
funding the research for development of an
antidote that would be used in overdose
situations

It would draw the meth out of the tissues and
decrease it's concentration in the body

Currently, charcoal is used for this
How are meth symptoms treated?

NIDA is studying 10 drugs that are used for other
conditions that might be useful for treating meth
addicts

Calcium-channel blockers may inhibit the excessive
release of neurotransmitters and reduce the
“reward” of using meth

Zofran is being studied because it works in
alcoholics

Tyrosine is the amino acid precursor to dopamine
and may increase the release of dopamine
How are meth addicts treated?

There are no severe physical withdrawal
symptoms


Individuals feel anhedonia (an inability to feel
pleasure) because dopamine levels are low
Antidepressants are prescribed to counteract
depression that former drug abusers feel

They are also being studied as possible treatments
because they boost neurotransmitters associated
with pleasure which are low in former abusers

The best treatment for addicts is cognitive
behavioral therapy
What are the medical applications
of methamphetamine?
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
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The metabolite of
methamphetamine is
amphetamine
The presence of a
methyl group
differentiates the two
(Kish, 2008)
Both drugs have the
same mechanism of
action
What are the medical applications
of methamphetamine?


Oral methamphetamine is Desoxyn

Used to treat ADHD in children, obesity, and
narcolepsy

Typical oral daily dose for children: 20-25 mg

Dose of meth needed for abusers to feel a
“significant rush”: 40-60 mg
Amphetamine, the metabolite of
methamphetamine is used in Adderall XR and
Dexedrine

Also prescribed for ADHD in children
What are the medical applications
of methamphetamine?


“In a study that directly compared the effect of
meth and amphetamine in humans, the
behavioral consequences and potencies of the
drugs were similar” (Kish, 2008)
The main difference between medicinal and
recreational meth is the onset

Oral meth has an onset of 20-60 minutes

Smokable forms have an onset of seconds to
minutes
Why is meth so addictive?


The exact reason for meth addiction is unknown
Imaging studies reveal that dopamine
transporters are greatly reduced in meth
abusers
Why is meth so addictive?

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Meth abusers are most likely addicted to the
access dopamine meth creates
This could involve a “pathological learning”
process in which dopamine facilitates learning
(Kish, 2008)
Dr. Linda Chang (Sommerfield, 2013) studied
former meth addicts and found a 24% decrease
in the normal number of dopamine transporters

This correlated with a decrease in motor function
and memory
Can meth addicts fully recover?


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With recovery, some of the meth-induced deficits in
dopamine function recover
Some areas of the brain show recovery after
prolonged abstinence, but other areas do not show
recovery
Long-lasting and permanent brain changes may result
from meth use (drugabuse.gov)
What are the long term effects of
methamphetamine use?
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Long-term neurological damage
Structural and functional deficits in areas of
brain associated with emotion and memory

Psychiatric and cognitive problems
Conclusion
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Methamphetamine abuse has a long, diverse
history
It continues to have a large impact on
communities despite efforts to control it
Meth works by increasing the amounts of
neurotransmitters in the brain
Meth is extremely addictive and has lasting
effects on its victim
Conclusion
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Meth is excreted primarily through the kidneys
Meth is absorbed through many different
pathways; different pathways result in different
effects
Meth has medical applications in patients with
obesity, narcolepsy, and children with ADHD
Methamphetamine's metabolite, amphetamine,
is also used in the treatment of children with
ADHD
References
[1] Public Health Response to Biological & Chemical Weapons: WHO Guidance. 2/1/2005, p214-228. 15p
[2] Endotoxin in Health and Disease, Helmut Brade, p 6
[3] Methamphetamine Abuse: A Perfect Storm of Complications, Timothy W. Lineberry M.D., J. Michael Bostwick, Mayo Clinic Proceedings, Volume 81, Issue 1,
Pages 77-84, January 2006
[4] Human Pharmacology of the methamphetamine stereoisomers, John Mendelson MD1, Naoto Uemura MD, PhD1, Debra Harris MD1, Rajneesh
P. Nath MD1, Emilio Fernandez MD1, Peyton Jacob III PhD1, E. Thomas Everhart PhD1 and Reese T. Jones MD1, Clinical Pharmacology &
Therapeutics (2006) 80, 403–420; doi: 10.1016/j.clpt.2006.06.013
[5] http://www.drugabuse.gov/publications/drugfacts/methamphetamine
[6] Stimulant Medications and Attention Deficit–Hyperactivity Disorder, N Engl J Med 2006; 354:2294-2295May 25, 2006DOI: 10.1056/NEJMc060860
[7] http://www.nhtsa.gov/people/injury/research/job185drugs/methamphetamine.htm
[8]Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations International Drug Control Programme B.
REMBERG, A. H. STEAD, Scientific Section, United Nations International Drug Control Programme, Vienna
[9] ADHD Drugs and Cardiovascular Risk, Steven E. Nissen, M.D., N Engl J Med 2006; 354:1445-1448 April6, 2006 DOI: 10.1056/NEJMp068049
[10] http://methoide.fcm.arizona.edu/infocenter/index.cfm?stid=164
[11]The clinical toxicology of metamfetamine, Schep LJ, Slaughter RJ, Beasley DM, Clin Toxicol (Phila). 2010 Aug;48(7):675-94. doi:
10.3109/15563650.2010.516752.
[12] http://www.sciencemag.org/content/300/5625/1479.2.full.pdf?sid=778dc757-085e-48f9-89ef-882a641205d5
[13] Drug Addiction, Jordi Camí, M.D., Ph.D., and Magí Farré, M.D., Ph.D., N Engl J Med 2003; 349:975-986September 4, 2003DOI: 10.1056/NEJMra023160
[14] Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review
Carl L Hart1,2,3, Caroline B Marvin1, Rae Silver1,4,5 and Edward E Smith1,6, Neuropsychopharmacology (2012) 37, 586–608; doi:10.1038/npp.2011.276;
published online 16 November 2011
References cont.
[1] Schepers, Raf J.F. "Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human
Volunteers." Clinical Chemistry, Jan. 2003. Web.
[2] "Drugs and Human Performance FACT SHEETS - Methamphetamine (and Amphetamine)." National Highway Traffic Safety Administration. N.p., n.d. Web.
[3] Durell, TM. "Prevalence of Nonmedical Methamphetamine Use in the United States."National Center for Biotechnology Information. U.S. National Library of Medicine, 25
July 2008. Web.
[4] Lineberry, Timothy W. "Methamphetamine Abuse: A Perfect Storm of Complications." Www.sciencedirect.com. Elsevier, Jan. 2006. Web.
[5] Anglin, Douglas. "History of the Methamphetamine Problem." Taylor and Francis. Journal of Psychoactive Drugs, 6 Sept. 2011. Web.
[6] Chan, P. "Fatal and Nonfatal Methamphetamine Intoxication in the Intensive Care Unit." Www.unboundmedicine.com. Journal of Toxicology, 1994. Web.
[7] "How Meth Destroys the Body." Www.PBS.org. PBS, n.d. Web.
[8] Cho, Arthur. "Patterns of Methamphetamine Abuse and Their Consequences."Www.tandfonline.com. Journal of Addictive Diseases, 12 Oct. 2008. Web.
[9] Bennett, B.A.; Hollingsworth, C.K.; Martin, R.S.; Harp, J.J. (January 1998). "Methamphetamine-induced alterations in dopamine transporter function". Brain Research 782 (12): 219–27.
[10]Winger, G. "Relative Reinforcing Strength of Three N-Methyl-D-Aspartate Antagonists with Different Onsets of Action." The Journal of Pharmacology and Experimental
Therapeutics, 6 Feb. 2002. Web.