Methamphetamine

By:

Laura Schmitt de LacerdaLaura LandonJorge 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 non-institutionalized 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?

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?

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?

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?

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?

Long-term neurological damage Structural and functional deficits in areas of

brain associated with emotion and memory Psychiatric and cognitive problems

Conclusion

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

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 (1-2): 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.