Download Psychotropics in the ED - Metroplex Society of Health

Designer Drugs:
Over the Counter
Killers
Jennifer L. Nelson, PharmD, BCPP
Parkland Health and Hospital System
Pharmacist Objectives
At the completion of this program, the participant will be able
to:
• Describe drug abuse patterns and trends among youth and
adult residents in Texas.
• Differentiate between the presenting symptoms of the novel
drugs of abuse and develop a treatment plan for each drug.
• State the changes in the Texas Prescription Monitoring
program.
• Explain the opportunities for pharmacist involvement in
Naloxone programs.
Pharmacy Technician
Objectives
At the completion of this program, the participant will be able
to:
• Describe drug abuse patterns and trends among youth and
adult residents in Texas.
• Differentiate the presenting symptoms of the novel drugs of
abuse.
• State the changes in the Texas Prescription Monitoring
program.
Substance Abuse Trends in
Texas
• Methamphetamine
• Forensic laboratories: outranks both cocaine and
cannabis
• #1 in Dallas, #2 in Houston and #4 in El Paso
• Seizures along Texas border up by 260% (western part)
and 420% on the lower border
• Heroin
• Younger users and a wider variety of ethnicities
• Seizures along western part of the Border up 352%
• New Mexican “white” heroin
Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.
Substance Abuse Trends in
Texas
• Cocaine
• Decrease in abuse
• Fewer coca bushes being grown in the Andes, product being
diverted to Europe
• Cannabis
• Drought in Mexico, gang warfare and increased border protection
 limited Mexican cannabis  increase in home-grown and
hydroponic cannabis
• Higher quality cannabis from Colorado
• Electronic cigarettes used for “vaping” of hash oil and “shatter”
• Synthetic Cannabis
• Many banned in Texas on September 1, 2011
• US banned more on July 9, 2012
• Importing chemicals from Mexico
Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.
Substance Abuse Trends in
Texas
• “Other Opiates”
• Pill mills
• Tramadol
• Fentanyl
• Patches vs. Powder
• PCP
• Abused more by females
• MDMA/Ecstasy
• Decreased use of “molly”: but has a higher potency
Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.
Substance Abuse Trends in
Texas Youth
• Alcohol
• Primary drug of abuse in Texas
• 51% of Texas secondary school students (grades 7-12) had every used
alcohol
• 25% had consumed alcohol in the last month
• Binge drinking: 9% reported
• New methods of use: inhaling or “smoking” alcohol
• Cannabis
• Decrease in Mexican imports, increase in indoor and hydroponic
growth
• Increase in potency (3.06% to 11.8%)
• New methods of use
• blunt cigars, flavored “papers” and “cones”
• Electronic cigarettes filled with tobacco or hash oil (“wax”, “shatter” or
“budder”)
• Brownies or cookies containing hash oil
Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.
Substance Abuse Trends in
Texas Youth
• Synthetic Cannabis
• 7% of students have ever used
• Heroin
• Use is growing among teenagers and young adults
• Increased use: Powdered “cheese heroin”, “Mexican Queso”
• Primary types in Texas: Mexican black tar and powdered brown
• Cocaine
• Decrease in use
• Increased demand for cocaine in Europe
• Decline in production
• Addition of levamisole: filler that will dilute the potency
• Transitioning to methamphetamine (easier to obtain)
• Cocaine inhalers are more likely younger users
Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.
Misuse vs. Abuse
• Misuse
• A drug is used for purposes
it is not intended for
• Not necessarily looking for
a “high”
• Signs of drug misuse
• Taking a dose at the wrong
time
• Forgetting to take a dose
• Stopping medication too
soon
• Accepting prescription
medication from a friend
• Taking drugs for reasons
other than what they were
prescribed for
• Abuse
• Use the drug for other
than it’s prescribed AND
for feelings of getting a
“high”
• Signs of drug abuse
• Using a drug to “get high”
• Using without a
prescription
• Exceeding a recommended
dose
• Chronic or repeated abuse
• Developed tolerance
Prescription Drug Abuse
• Gabapentin
• Structurally related to GABA
• Used by patients in methadone programs
• Codeine or Hydrocodone cough syrup
• “lean” or “syrup”
• Mixed with soft drinks or cocktails
• Can also be used undiluted
• Benzodiazepines
• Alprazolam
• Pseudoephedrine
• Used to produce very small amounts of methamphetamine ~ 1%
• Dextromethorphan
• Produce hallucinogenic effects when taken in large quantities
Mersfelder TL, Ann Gabapentin: Abuse, dependence and withdrawal. Pharmacother. 2016, 229-233
Quetiapine Misuse/Abuse
• Quetiapine is approved for the treatment of Schizophrenia
and acute episodes of Bipolar disorder. May also be used for
adjunctive treatment of depression.
• 13.6 million Americans have a mental health disorder listed
above
• >54 million prescriptions written per year
• Side effects: constipation, nausea, orthostasis, increased
appetite, weight gain, and sedation
• Produces calming and hallucinogenic effects
• Baby heroin, Squirrel, Q-ball, Quell, Snoozeberries and Susie-Q
• Misuse through crushing and snorting
• Dissolve into water-based solutions and inject intravenously
• AstraZeneca released extended-release version to help deter
abuse
www.dualdiagnosis.org
Addiction
• A state in which an
organism engages in a
compulsive behavior,
even when faced with
negative consequences
• Natural rewards vs.
artificial rewards
• Reward pathway:
ventral tegmental area
(VTA), nucleus
accumbens and the
prefrontal cortex
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Addiction
• Properties of addiction
• Directly related to the reinforcing properties of a drug
• Related to the effects of the drug itself
• Psychoactive drugs alter normal neurochemical
processes
• Mimic the action of the neurotransmitter
• Alter the activity of a receptor
• Acting on the activation of second messengers
• Directly affecting intracellular processes that control
normal functioning
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Novel Psychoactive Substances
• Synthetic drugs
• Created using man-made chemicals rather than
natural ingredients
• Designer drugs
• A synthetic version of an illegal drug that is slightly
altered in order to avoid classifying it as illegal
• Sold in various locations
• Internet, certain stores as “herbal smoking blends”
• Labeled as “not for human consumption”
• Users are unsure of what the drug may contain
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Novel Psychoactive Substances
• >650 new designer drugs submerged on Europe in the
past 10 years
• Mostly produced in China and South East Asia
New Psychoactive Substances
400
200
0
2010
2011
2012
2013
2014
Novel Psychoactive Substances
Classifications
• Psychotropic Effect: Stimulants,
Empathogens/Entactogens or Hallucinogens
• Chemical Family: Phenethylamines, Amphetamines,
Cathinones, Piperazines, Pipradrols/Piperidines,
Aminoindanes, Benzofurans, and Tryptamines
• Synthetic cannabinoids: include a large number of
agents which act upon CB1 receptor (have hallucinogenic
and stimulant properties)
• Usually classified based on their pharmacological properties
• Dopaminergic, noradrenergic or serotonergic
pharmacologic effects
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Novel Psychoactive Substances
Synthetic Cannabinoids
• “Spices”: herbal mixtures
• Many substance names start with the initials of the chemist (i.e.
AM followed by numbers)
• Act as agonists at the CB1 receptor
• Produce similar effects and toxicity to tetrahydrocannabinol
(THC)
• Not detective by UDS for THC
• More severe psychosis and agitation, and increased
sympathomimetic effects (due to lack of cannabidiol)
• Common symptoms: agitation, aggression, paranoid thinking and
anxiety
• 2nd generation: in US and Europe: severe toxicity  seizures,
cardiac toxicity, acute kidney injury
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Synthetic Cannabinoids
Continued
• 2013 US government report: Emergency department visits in
2011 increased by 2.5 times
• 2014: Texas dealer of K2 was linked to 120 overdoses in
Austina nd Dallas in one week alone
• Multiple car accidents linked to smoking of synthetic
marijuana
• Effects on the Mind
• Confusion, extreme anxiety, severe paranoia, delusions,
hallucinations
• Effects on the Body
• Nausea, vomiting, acute kidney injury, increased blood pressure,
convulsions, seizures, strokes
“Global Synthetic Drugs Assessment,” UN Office on Drugs and Crime, 2014
Novel Psychoactive Substances
Continued
• Synthetic Cathinones
• Contain a ketone group at the β-position of the amphetamine
• Most common: mephedrone, methylone and MDPV
• Others: ethylone, methedrone, naphyrone, flephedrone, 3fluoromethcathinone (3-FMC), pentylone, buphedrone, α-PVP, etc
• Can have effects similar to cocaine but also MDMA
• Psychotropic effects similar to MDMA but with enhanced
psychostimulation similar to cocaine
• Toxicity (similar to amphetamine): hypertension, hyperthermia, euphoria,
locomotor activation and hallucinations
• Noted to be more addictive then cocaine
• Ring substituted phenethylamines and amphetamines (2-C and 2-D
series)
•
•
•
•
Examples: 2C-B and 2C-I as well as DOM, DOB and DOI
Increased hallucinogenic properties
Intoxication: hallucinations, Nausea, tachycardia, agitation, ergotism
25I-NBOMe: Severe and fatal intoxications: agitation, hallucinations,
seizures, hyperthermia
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Bath Salts
•
•
•
•
Group of similar substance
Referred to as synthetic stimulants
Most of the substance are banned in the US
Users may snort, inject, take rectally, mix it with food/drink,
“bombing”, or smoke it
• Effects on the Mind
• Insomnia, euphoria evolving to paranoia, nightmares,
hallucinations, suicidal thoughts, violent behavior
• Effects on the Body
• Mephedrone stink, fever, sexual dysfunction, nosebleeds,
dizziness, chest pain and heart attacks, brainstem herniation,
seizures
“Global Synthetic Drugs Assessment,” UN Office on Drugs and Crime, 2014
Novel Psychoactive Substances
Continued
• Kratom
• Opioid-like tropical tree from Southeast Asia
• Used to alleviate musculoskeletal pain, increase energy,appetite and
sexual desire
• Thought to be a “natural alternative” for chronic pain and opioid
withdrawal
• Smoked, ingested or brewed
• Adverse effects: nausea, vomiting, constipation, anorexia and
palpitations
• Acetyl Fentanyl
•
•
•
•
Opioid analgesic
Similar to fentanyl
Transdermal patch or IV
Euphoria, altered mood, miosis, constipation and respiratory
depression
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Novel Psychoactive Substances
Continued
• Salvia
• Active compound: salvironin A
• Selective high efficacy kappa-opioid receptor
agonist
• Causes hallucinogenic-like, depression-like and anxiety-like states
• NBOMe
• Most common: 25C-NBOMe
• Legally replaced LSD
• Administration route: buccal, sublingual, nasal, oral, parenteral,
rectal and inhalation
• Symptoms: nausea, vomiting, dizziness, diarrhea, headaches and
hallucinations
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Novel Psychoactive Substances
Continued
• Phenethylamines and Amphetamines
• Amphetamine derived MDMA is one of the most widely used
recreational drugs
• Prototypical empathogen or entactogen  produces empathy or
“being touched”
• Enhances sociability
• Para-(4)-phenyl-substituted (serotonergic) amphetamines
• Paramethoxyamphetamine (PMA) and
Paramethoxymethamphetamine (PMMA)
• Typically sold as ecstasy
• Higher morbidity and mortality hyperthermia (stronger then
MDMA)
• Potent noradrenaline and serotonin transporter inhibitors
• Examples: 4-methylthioamphetamine (4-MTA) and methedrone
(β-keto-PMMA)
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Novel Psychoactive Substances
Continued
• Benzofurans and Benzodifurans
• Ring substituded amphetamines
• Structurally related to MDMA
• Effects related to MDMA but more intense
• Examples: 6-APB and 5-APB
• ADE: nausea, sympathomimetic stimulation and agitation
• Also known as the “fly” drugs (bromo-dragon fly, 2C-B-fly)
• Paranoia, agitation, tachycardia and hyperthermia
• Piperazines
• Found in ecstasy as substitutes for MDMA
• Examples: m-CPP and TFMPP
• Less desirable psychotropic effects and more adverse effects
• Dysphoria, anxiety and nausea
• Benzylpiperazine (BZP): toxicity  hallucinations, agitation, seizures
and hyperthermia
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Novel Psychoactive Substances
Continued
• Aminoindanes
• Examples: MDAI and 5-IAI
• Less neurotoxic than MDMA
• Pipradrols/Piperidines
• “Ivory Wave”: contains 2-DPMP or D2PM
• Similar to methylphenidate
• Long-lasting clinical toxicity: sympthomimetic stimulation,
hypertension, agitation, hallucinations and insomnia
• Tryptamines
•
•
•
•
•
•
Natural tryptamine: psilocybin and dimethyltryptamine (DMT)
Ergolines: include protypic hallucinogen: LSD
Examples: alpha-methyltryptamine (AMT) and 4-HO-MET
Serotonin syndrome and sympathomimetic toxicity may occur
Hallucinogenic properties (typically visual)
Usually nonaddictive
Andrabi S, et al. New drugs of abuse and withdrawal syndrome. Emerg Med Clin N Am. 2015: 779-795
Novel Psychoactive Substances
Treatment
Substance
Leading Acute Toxicity
PMA
Serotonergic toxidrome, hyperthermia, nausea,
seizures, fatalities
Mephedrone, methylone
Sympathomimetic toxidrome, agitation, vomiting,
psychosis, chest pain, seizures, insomnia
MDPV, α-PVP
Psychosis, agitation, combative behavior,
sympathomimetic toxidrome, chest pain,
prolonged insomnia
BZP
Mostly sympathomimetic toxicity, agitation,
anxiety
“fly” drugs
Psychosis, agitation, hyperthermia,
sympathomimetic toxicity, vasospasm, limb
pain/ischemia, seizures, fatalities
AMT
Serotonergic and sympathomimetic toxidrome,
psychosis, agitation, hyperthermia, nausea
Synthetic cannabinoids
Psychosis, agitation, anxiety, sympathomimetic
toxidrome, chest pain, myocardial infarction,
renal injury, seizure, vomiting
Novel Psychoactive Substance
Treatment Continued
• Establish safety
• Many have an altered sensorium
• Poor historians
• Ensure patient’s airway and adequate breathing
• CNS depression
• Treatment is mainly supportive
• Heart rate, blood pressure and body temperature
• Hypertension and Hypotension have both been seen
• Hypertension  nitrates (avoid β-blockers)
• Laboratory tests: electrolytes, creatine kinase, liver enzymes and
cardiac enzyme
• Treatment of a sympathomimetic toxidrome
• Benzodiazepines and fluid replacement
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Novel Psychoactive Substance
Treatment Continued
• Consider Naloxone administration
• Physical cooling and relaxation may be needed in severe
hyperthermia cases
• Behavioral therapies
• Yet to be tested
• Once patient is in recovery, a thorough assessment should
occur
• Trace the history of the elicit substance
Pompei P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2
Opioid Overdose
• Examples of opioids: morphine, heroin, oxycodone and
methadone
• Signs and symptoms: “opioid overdose triad”
•
•
•
•
Respiratory depression
Decreased level of consciousness
Pinpoint pupils
Other symptoms
• Seizures and muscle spasms
• Effects influence by: dose, tolerance and presence of active
metabolites
• Treatment
• Identify the specific drug, dose and formulation
• Identify co-exposures
• Administration of Naloxone
Texas Pharmacist Naloxone
Standing Order
• Naloxone
• µ-opioid receptor inverse agonist
• Antagonist action
• Used to block the effects of opioids
• Reverses the depression of the central nervous system and respiratory
system caused by opioids
• Competes for the opiate receptor sites within the CNS, preventing the
action of both endogenous and xenobiotic opiates on these receptors
• Poorly absorbed orally
• Intravenous: effect seen within
2 minutes
• Intramuscular: effect seen within
5 minutes
• Dose: 0.4-2mg, may repeat doses every 2
minutes until the max dose of 10mg has
been reached
Naloxone Hydrochloride. The American Society of Health-System Pharmacists. Retrieved November 5, 2016.
Naloxone Standing Order
• A standing order is a physician’s order that can be carried out
by other health care workers when predetermined conditions
have been met.
• A doctor with prescriptive authority issues a written order that
naloxone can be distributed by designated people to those who
meet the criteria outlines in the document
• Can receive naloxone without ever meeting the doctor who
prescribed it
• Statewide written order
• Physician General issues a statewide written order that naloxone
can be distributed by designated people
• >50% of the US states now have naloxone standing order
programs
http://naloxoneinfo.org/case-studies/standing-orders
Naloxone Access and Good
Samaritan Laws
• 2001: New Mexico became the first state to amend its
laws to improve naloxone administration
• 2014: >150,000 laypeople had received training and
naloxone kits
• Reported reversing >26,000 overdoses
• June 22, 2015
• 46 other states and the District of Columbia made laws
improving access
• June 22, 2016
• All but three states (Kansas, Wyoming, Montana) had
passed legislation designed to improve naloxone
access
https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf
Naloxone Access and Good
Samaritan Laws
https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf
Saving Lives Initiative
• Includes allowing pharmacists to administer epinephrine in an
emergency situation
• Senate Bill 1462 by Sen. Royce West (D-Dallas)
• Allows authorized medical personnel to prescribe naloxone either
directly to a third-party patient or through a standing order
• Created a physician-signed standing order (statewide
prescription)
• Highest risk are the elderly and medically ill who are already
medically compromised.
TPA’s Naloxone Standing Order Now Available. Retrieved from http://www.texaspharmacy.org/news/303222/TPAsNaloxone-Standing-Order-Now-Available.htm. November 2016
Texas Pharmacist Naloxone
Standing Order
• To facilitate the prescribing of opioid antagonists
• To combat the effects of opioid overdose
• Formulations of opioid antagonist
•
•
•
•
•
Intramuscular Naloxone
Naloxone Auto-Injector
Intranasal Naloxone
Naloxone Nasal Spray
Any other opioid antagonist formulation permitted under the law
• May dispense any other items necessary for administration
• Syringes and mucosal atomization devices
TPA’s Naloxone Standing Order Now Available. Retrieved from http://www.texaspharmacy.org/news/303222/TPAsNaloxone-Standing-Order-Now-Available.htm. November 2016
Texas Pharmacist Naloxone
Standing Order
• Dispense to: a person at risk of overdose; also to a family
member, friend or other person in a position to assist such a
person
• Prior to dispensing
• Pharmacist shall complete and obtain a certificate of completion
of a one hour Texas accredited course provided by an
Accreditation Council for Pharmacy Education which includes:
• When a pharmacist should or should not dispense
• How to work with the patient in selecting which opioid antagonist to
dispense
• When to administer
• Standing order shall be maintained at the pharmacy
• Pharmacist must maintain an active license and remain in
good standing with the TSBP
TPA’s Naloxone Standing Order Now Available. Retrieved from http://www.texaspharmacy.org/news/303222/TPAsNaloxone-Standing-Order-Now-Available.htm. November 2016
Distribution, Possession and
Administration
• Permits groups such as nonprofits, drug treatment centers and
other organizations to distribute naloxone
• Allows any person to possess naloxone (even if they do not
have a prescription for it)
• Allows any person, who acts in good faith and with reasonable
care, to administer naloxone
• Immune from criminal prosecution, civil liability and sanction
under professional licensing statutes
Naloxone Pricing
• Naloxone has increased by as much as 17-fold since 2014
• Naloxone auto-injector $4,500 (previous wholesale price
$690)
• Insurance coverage
• Texas Medicaid does cover all formulations of naloxone
Krokodil
(desomorphine)
• Noted as the MOST devastating designer drug on the street
market
• Used as a pain reliever in Switzerland in the early 1930s
• Appeared on the black market in the early 2000s
• Reports of over 100,000 people having injected the drug in 2011
• Schedule I controlled substance in the US
• Subject to annual aggregate manufacturing quotas
• In 2014 the quota was 5 grams
• Entirely user made and distributed
• Regulated: codeine and hydrochloric acid
• Unregulated: gasoline, paint thinner, iodine and red phosphorous
(from matchstick heads)
Alves EA, et al. Forensic Sci Int. 2015 Apr; 249: 207-213.
Krokodil
• Transient opiate like high
• Injected every couple hours
• Onset of effect ~ 2-3 minutes
• Euphoria lasts between 1.5-2 hours
• 30,000 people killed each year in Russia
• Users are reported to rarely live past a
year after they start taking it
• Life expectancy of three years maximum
Alves EA, et al. Forensic Sci Int. 2015 Apr; 249: 207-213.
Krokodil
Signs and Symptoms
Short Term
Decrease in overall health
Weight loss
Lethargy
Inability to remain awake
Depression
Anxiety
Flu-like symptoms
Long Term
Blood vessel damage
Skin and soft tissue
infections
Osteomyelitis
Pneumonia
Meningitis
Memory loss
Organ failure
Alves EA, et al. Forensic Sci Int. 2015 Apr; 249: 207-213.
Krokodil
Haskin A, Kim N, Aguh C. JAAD Case Rep. 2016 Mar; 2(2): 174-176
Krokodil Treatment
• Medically monitored – inpatient admission
• Intensive medical attention in addition to addiction
treatment
• Symptoms may last up to a month after
discontinuation
• Usual symptoms: insomnia, nausea, diarrhea,
extreme muscle cramping, depression, body
aches and overall sickness
• Residual symptoms: vacant gaze, speech
impediment and erratic movements
• Opioid antagonist can be utilized
Alves EA, et al. Forensic Sci Int. 2015 Apr; 249: 207-213.
Questions???
References
• Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community
Epidemiology Work Group, June 2014.
• Mersfelder TL, Nichols WH. Ann Gabapentin: Abuse, dependence and withdrawal. Pharmacother.
2016, 229-233
• Seroquel Abuse. Retrieved from http://www.dualdiagnosis.org/seroquel-abuse/. November 2016
• “Global Synthetic Drugs Assessment,” UN Office on Drugs and Crime, 2014.
• Andrabi S, Greene S, Moukkadam N, Li B. New drugs of abuse and withdrawal syndrome. Emerg
Med Clin N Am. 2015: 779-795
• Pompei P, Micioni Di Bonaventura MV, Cifani C. The “Legal Highs” of Novel Drugs of Abuse. J Drug
Abuse. 2016, 2:2.
• Naloxone Hydrochloride. The American Society of Health-System Pharmacists. Retrieved
November 5, 2016.
• Naloxone overdose and Good Samaritan Laws. Retrieved from
https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf
• Standing orders. Retrieved from http://maloxoneinfo.org/case-studies/standing-order. November
2016
• TPA’s Naloxone Standing Order Now Available. Retrieved from
http://www.texaspharmacy.org/news/303222/TPAs-Naloxone-Standing-Order-NowAvailable.htm. November 2016
• Alves EA, et al. The harmful chemistry behind krokodil (desomorphine) synthesis and mecahnisms
of toxicity. Forensic Sci Int. 2015 Apr; 249: 207-213.
• Haskin A, Kim N, Aguh C. A new drug with a nasty bite: A case of krokodil-induced skin necrosis in
an intravenous drug user. JAAD Case Rep. 2016 Mar; 2(2): 174-176