Transcript Desomorphine - UNM Biology

TOXIN: DESOMORPHINE
STREET NAME: KROKODIL
Kimberly Quam
Blake Sims
Katy Hughes
PURPOSE & INTENT
• The purpose of this presentation is to bring awareness
to an EXTREMELY toxic drug that is not very well known.
• Many of us know about the drug crisis in Asia and the
Middle East, but few have even heard of a fairly new
drug called krokodil (pronounced crocodile).
• This drug is EXTREMELY toxic to the body and has been
called the “drug that eats junkies”
• Krokodil is a crude form of desomorphine that is used
as a replacement for heroin.
• To put it into perspective… Russia’s krokodil problem
can be compared to New Mexico’s
methamphetamine problem.
• Our intent is to explain exactly what
desomorphine/krokodil is, how it effects the body, and
what the future outlook is for users in Russia.
INTRODUCTION
The importance of desomorphine:
• Desomorphine was originally invented in 1932 in the U.S. as a possible
alternative to morphine. Scientists were looking for a strong analgesic with
less side effects, they isolated both desomorphine and methadone.
• Desomorphine has a quicker onset, decreased side effects (such as
nausea or respiratory depression), but a shorter duration as compared to
morphine.
• Even though desomorphine seemed to be a good morphine alternative,
researchers found that it lead to rapid addiction and ceased professional
usage.
• In the early 2000’s, desomorphine synthesis started to emerge on the
streets of Russia. Drug users found that they could easily produce
desomorphine from cheap compounds that were fairly easy to obtain
and combine.
INTRODUCTION (CONT.)
• Like heroin, desomorphine is almost always injected intravenously.
• The “home-cooked” substance was quickly nicknamed krokodil
because of the scaly, green appearance that users skin began to turn as
they used the drug.
• The term krokodil refers to the street form of desomorphine which is highly
toxic and impure.
• Many heroin users in Russia have switched from heroin to krokodil
because it is significantly cheaper to produce.
• Heroin is an expensive habit and users that do not have enough money
to sustain their addiction avoid withdrawal by switching to krokodil. Users
cannot avoid the toxic and harmful effects of desomorphine and often
die within 1-2 years of abuse.
WHAT IS DESOMORPHINE?
• A semi-synthetic opioid: a chemical compound that binds to one or more opium
receptors in the body
• Opium receptors are G-protein receptors; opioids are ligands.
• A derivative of morphine:
• Morphine is a potent drug made from the opium poppy that is used for severe pain
(isolated in 1804).
• Biochemical composition of desomorphine: see figure 1
• Starts with the compound α-chlorocodide (a derivative of codeine where the 6hydroxy group is replaced by Cl).
• Catalytic reduction of a-clorocodide yields dihydrodesoxycodeine which is further
demethylated into desomorphine.
• A sedative: calming/sleep inducing drug
• An analgesic: pain relieving drug
figure 1
BLOOD  BRAIN
• Users inject desomorphine (krokodil) intravenously using a hypodermic needle
• Arm veins are initially used, then more dangerous spots like the femoral vein in
the groin must be used as veins collapse
• The uptake of desomorphine in the brain is nearly complete after 30 seconds
• Desomorphine is converted to morphine by enzymes
• Morphine binds to opiate receptors in the brain
• In the reward pathway [VTA, nucleus accumbens]euphoria
• And in the pain pathway [thalamus, brainstem, and spinal
cord] analgesia
• The thalamus and the brainstem are involved in opiate
addiction
• Withdrawal symptoms are generated when the opiate receptors
in the thalamus and brainstem are deprived of morphine
MECHANISM OF ACTION:
OPIOID RECEPTORS
• Scientists have found 3 major types of opioid receptors in the body: μ, δ and
k
• All 3 produce analgesia when an opioid binds
• Morphine has a higher affinity for m receptors than for other opioid receptors
• μ receptors produce physical dependence
• Opioid receptors are present in many regions of the nervous system involved
in pain transmission and control
• Presynaptic action of opioids inhibit neurotransmitter release [this is their
major effect in the nervous system!]
• Opioids produce analgesia in the nervous system by inhibition of
neurotransmitter release from the primary afferent terminals in the spinal
cord & activation of inhibitory controls in the midbrain
MECHANISM OF ACTION: INHIBITOR
• Opioids inhibit neurotransmitter release by inhibiting Ca2+ entry by enhancing
outward movement of K + ions or by inhibiting adenylate cyclase [the enzyme
that breaks down ATP to form cAMP]
• All 3 types of opioid receptors couple to adenylate cyclase.
• Inhibition of adenylate cyclase results in inhibition of neurotransmitter release.
figure 3
MECHANISM OF ACTION: G-PROTEIN
SIGNALING PATHWAY
• Opioid receptors are coupled to G-proteins
• Morphine binds to the G-protein receptor
• [system is turned ON] GDP dissociates from
the a-subunit and GTP takes its place 
conformational change causes desomorphine
to dissociate from the receptor  a-subunit
bound to GTP dissociates from the β and γ
subunits  produces the effect  enzymatic
activity of the a-subunit causes GTP to be
converted back to GDP  a-subunit reassociates with the β and γ subunits to return
the complex to its normal state [system is
turned OFF]
figure 2
DESOMORPHINE EFFECTS
• Therapeutic:
•
•
•
•
Intense euphoria
Transcendent relaxation
Reduces severe pain
Inhibits coughing
• Adverse:
•
•
•
•
•
Intense physical dependence
Inability to communicate effectively
Extremely nephrotoxic
Mild hallucinations
Risk of contracting HIV/Hep C/other bloodborne diseases increases
RUSSIA & HEROIN/KROKODIL
DEPENDENCE
• Russia has the highest documented rate of heroin abuse in the world
• Low socio-economic status and high levels of poverty are major
contributors to this problem
• Efforts to reduce the flow of Afghan heroin into Russia bring limited success
• This has caused street prices of heroin to increase
• Those addicts who can't afford their next hit turn to krokodil
• Krokodil use is worse in isolated parts of Russia where users are less likely to
be able to find heroin
• Codeine based tablets are easy to find and (until June 2012) available
over-the-counter
*krokodil refers to the “home-cooked,” highly toxic form of desomorphine in Russia
“KROKODIL” [HOME MADE
DESOMORPHINE] IN RUSSIA
Krokodil is synthesized using the following compounds:
• Codeine: obtained from over the counter cold
medications (tablets) such as: Codterpin, Codelac,
Sedal M.
• Iodine: obtained often illegally in the form of iodine
crystals
• Red Phosphorus: found in matchbook strike plates,
flame retardants
• Lighter Fluid
• Industrial Cleaning Oil
*Caffeine, paracetamol, and diphenhydramine may also be added to the mix. Tropicamide (found in
eye drops) may also be added to prolong the experience.
**Preparation takes about 30 minutes to an hour to achieve final product. These “ingredients” are fairly
easily obtained and the cost to produce krokodil is negligible.
“KROKODIL” [HOME MADE
DESOMORPHINE] IN RUSSIA
• Krokodil is extremely toxic due to crude production methods and little
purification.
• Krokodil synthesis is very similar to methamphetamine synthesis
• Meth is made with pseudoephedrine while desomorphine is made with
codeine
• But desomorphine made this way (by cooking it illegally) is highly
impure and contaminated with various toxic and corrosive byproducts
• Heroin v. Krokodil
• Heroin users spend roughly $100/dose
• Codeine tablets are available for ~$7/pack in Russia.
CODEINE: THE MAIN INGREDIENT
• Codeine [3-methylmorphine] is an opiate and an isomer of morphine
• Codeine has analgesic, sedative properties, and suppresses coughing.
• It is also an antitussive, antidiarrheal, antianxiety, and antihypertensive
• Codeine adverse effects:
• Drowsiness, constipation, itching, nausea, vomiting, hypotension,
dehydration, urinary retention, depression
• Prolonged usage can lead to: diminished libido, apathy, memory loss
• Codeine  morphine transformation occurs in the liver by cytochrome
P450 (specifically CYP2D6)
KROKODIL TOXICITY
• Red phosphorus destroys bone and damages the central nervous system
which can lead to brain damage.
• Iodine weakens muscle contractibility resulting in atrophy.
• Harmful chemicals used to synthesize desomorphine disrupt the normal
balance of minerals and build up in the liver and kidneys
• causes organ failure
• teeth typically rot away
• skin tone discolors to a shade of green and becomes scaly
• tissue necrosis often progresses to the point where bone is visible
• gangrene is common and amputation is often necessary
• more than one-third of users become ill with hepatitis C, and most die
within one to two years
*See the following slide for supplementary figures (WARNING: GRAPHIC)
TOXIC EFFECTS
These are examples of the harmful physical effects of krokodil abuse on the body.
DESOMORPHINE: “POOR MAN’S HEROIN”
DESOMORPHINE
Potency:
Duration of effects:
Length of withdrawal:
Physical withdrawal pain:
Life expectancy:
8-10x more potent than morphine
30-90 minutes
1 month
1 month (often addicts are given a
strong tranquilizer to keep pain at an
endurable level)
1-2 years
• Krokodil addicts are trapped in a 24 hour cycle of cooking
and injecting the drug to avoid unbearable withdrawal
symptoms. It often becomes their “job” to feed their
addiction.
HEROIN
3-5 hours
5 days
5-10 days
6-8 years
RUSSIA: A COUNTRY IN CRISIS
• Russia is plagued with heavy smoking, extreme alcoholism, pollution, high poverty
levels, low birth rates, and an increasing amount of HIV/AIDS cases
• The United Nations project that the Russian population will shrink to 116 million by
2050
• The population is currently142 million
• Moscow now awards money to mothers bearing two or more children
• Moscow has a ban on methadone and a heavy prison sentence for anyone
caught with the synthetic opiate
• This is a major problem in treating heroin addiction
• This causes doctors to medicate heroin addicts with tropicamide (an ingredient in eye
drops)
• It is estimated that about 3 million Russians are drug addicts
• Most between the ages of 18-39
• 90% of HIV/AIDS cases in Russia are due to needle sharing (estimated 1 million
Russians have HIV/AIDS)
RUSSIA’S WAR ON DRUGS
• Only recently has Russia acknowledged and
started to deal with their huge drug problem
• Krokodil abuse is second to heroin in Russia
[remember, Russia has the highest rates of heroin
abuse in the world]
• The government attributes the drug problem to
the fall of the Soviet Union
• They blame the Taliban in Afghanistan as the reason why intravenous use of heroin has
skyrocketed
• It is estimated that 90% of the world’s opium is grown in Afghanistan
• Russian authorities have urged the U.S. military to bring the war on drugs to
Afghanistan to try to limit the amount of heroin entering into Russia
• The American military influence in Afghanistan has not limited the amount of opium
produced
RUSSIA’S WAR ON DRUGS
• As of June 1, 2012, all codeine based tablets in Russia are now prescription only.
Over-the-counter sales have been banned.
• This is the direct response to the growing production of krokodil in Russia
• Reportedly this has not negatively effected the production of krokodil
• This is the most the Russian government has done to resolve the problem
OUTLOOK FOR USERS SEEKING
TREATMENT
• Rehabilitation facilities in Russia are either privately owned or funded by foreign
countries
• Russia’s drug treatment technology is referred to as "narcology"
• Narcology is basically an old branch of Russian psychiatry
• Treatment consists only of detox
• Treatment may be followed with a course of antipsychotic medications or
barbiturates
• Krokodil addicts are given strong tranquilizers while they detox
• Any sort of psychological evaluation with supplementary behavioral therapy is
rare
• Addicts are also rarely taught about how to live a drug-free lifestyle after detox
• Treatment centers that offer more extensive treatment likely use hypnosis to
implant the idea if the addict uses drugs again, they will die
OUTLOOK FOR USERS SEEKING
TREATMENT
• Rehab centers in Russia resemble jails more than treatment facilities
• Patients may be shackled to beds or placed in cells for the duration of “treatment”
• Only about 1/3 of Russia has treatment
facilities at all
• Some studies show that about 90% of
addicts relapse within a year after
treatment
WRAPPING IT UP
• Desomorphine is a potent semi-synthetic opioid
that was invented in the U.S. in 1932, but
deemed too addictive for professional use.
• Once desomorphine makes it into the
bloodstream, it is enzymatically converted into
morphine. Morphine binds to a G-protein
receptor where it turns on the signaling pathway
and causes both analgesic and sedative
effects.
• Krokodil is a home-cooked version of
desomorphine which started to appear Russia in
the early 2000’s.
• Krokodil is used as a substitution for heroin;
called “poor man’s heroin”. Heroin is expensive
and can be hard to obtain in Russia.
WRAPPING IT UP
• Krokodil is crudely made from codeine, iodine,
red phosphorous, and other toxic chemicals.
The mixture is hardly purified and extremely
toxic.
• Krokodil addicts experience gangrene leading
to amputation, tissue necrosis, organ failure,
and often death within 1-2 years.
• Krokodil users in Russia have a bleak outlook.
Treatment programs are hard to come by and
rarely effective.
• The Russian government has recently opened
their eyes to the epidemic, but much more
needs to be done in order to successfully help
citizens with severe drug addictions to toxic
drugs like krokodil.
WORKS CITED
Himmelsbach, C.K. “Studies of certain addiction characteristics of (a) dihydrommorphine
(“paramorphan”), (b) dihydrodesoxymorphine-d (“deso-morphine”), (c)
dihydrodesoxycodeine-d (“desocodeine”), and (d) methyldihydro-morphinone
(“metopon”).” Journal of Pharmacology and Experimental
Therapeutics 67.2 (1939):
2239-249.
Wright, C. and Barbour, F. A. “The respiratory effects of morphine, codeine and related substances V>
compounds derived from morphine and dihydromorphine by substitution in the 6-carbon
position.” Journal of Pharmacology and Experimental Therapeutics 61.4 (1937): 422-439.
Savchuk, S.A., Barsegyan, S.S., Barsegyan, I.B. “Chromatographic study of expert and biological
samples containing desomorphine.” Journal of Analytical Chemistry 63.4 (2008): 361-370.
Lee, L.E. “Studies of morphine, codeine, and their derivatives XVI. Clinical studies of morphine,
methyldihydro-morphinone (metopon) and dihydrodesoxy-morphine-d (desomorphine).”
Journal of Pharmacology and Experimental Therapeutics 78.4 (1943): 375-385.
WORKS CITED
Gayathri, Amrutha. "Krokodil: Inexpensive Mind-altering Drug Made from Head-ache Tablets Kills Thousands."
International Business Times, 28 June 2011. Web.
Garcia, Marlene, and Daniel Lindley. "What Is Desomorphine?" WiseGeek. Conjecture, 21 Feb. 2013.
Chahl, Loris A. "Opioids - Mechanisms of Action." Australian Prescriber. Experimental and Clinical
Pharmacology, July 1996. Web.
"Desomorphine Aka Krokodil." Drug Alcohol Rehab Asia, n.d. Web.
"Over-the-counter Sales of Drugs That Contain Codeine Prohibited in Russia." Rylkov Foundation RSS. N.p.,
June 2012. Web.
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Jan. 2011. Web.
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