Designer Drugs: Over the Counter Killers - PowerPoint Presentation

Slide1

Designer Drugs: Over the Counter Killers

Jennifer L. Nelson,

PharmD

, BCPP

Parkland Health and Hospital System

Slide2

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.

Slide3

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.

Slide4

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.

Slide5

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, 2011US banned more on July 9, 2012Importing chemicals from Mexico

Maxwell JC. Substance Abuse Trends in Texas: June 2014. Proceedings of the Community Epidemiology Work Group, June 2014.

Slide6

Substance Abuse Trends in Texas

“Other Opiates”

Pill mills

Tramadol

Fentanyl

Patches vs. Powder

PCP

Abused more by femalesMDMA/EcstasyDecreased 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.

Slide7

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

CannabisDecrease in Mexican imports, increase in indoor and hydroponic growthIncrease 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.

Slide8

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 brownCocaineDecrease in useIncreased 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.

Slide9

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 soonAccepting prescription medication from a friendTaking 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

Slide10

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 undilutedBenzodiazepinesAlprazolam

Pseudoephedrine

Used to produce very small amounts of methamphetamine ~ 1%

DextromethorphanProduce hallucinogenic effects when taken in large quantities

Mersfelder

TL,

Ann

Gabapentin: Abuse, dependence and withdrawal.

Pharmacother

. 2016, 229-233

Slide11

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 effectsBaby heroin, Squirrel, Q-ball, Quell, Snoozeberries

and Susie-Q

Misuse through crushing and snorting

Dissolve into water-based solutions and inject intravenouslyAstraZeneca released extended-release version to help deter abuse

www.dualdiagnosis.org

Slide12

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

Slide13

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 messengersDirectly 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

Slide14

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

Slide15

Novel Psychoactive Substances

>650 new designer drugs submerged on Europe in the past 10 years

Mostly produced in China and South East Asia

Slide16

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 CB

1

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

Slide17

Novel Psychoactive Substances

Slide18

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 CB

1

receptor

Produce similar effects and toxicity to tetrahydrocannabinol (THC)

Not detective by UDS for THCMore severe psychosis and agitation, and increased sympathomimetic effects (due to lack of

cannabidiol

)

Common symptoms: agitation, aggression, paranoid thinking and anxiety2nd 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

Slide19

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 marijuanaEffects on the MindConfusion, extreme anxiety, severe paranoia, delusions, hallucinationsEffects 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

Slide20

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, 3-fluoromethcathinone (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

Slide21

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 BodyMephedrone 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

Slide22

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 withdrawalSmoked, ingested or brewedAdverse effects: nausea, vomiting, constipation, anorexia and palpitations

Acetyl Fentanyl

Opioid analgesic

Similar to fentanylTransdermal patch or IVEuphoria, 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

Slide23

Novel Psychoactive Substances

Continued

Salvia

Active compound:

salvironin

A

Selective high efficacy kappa-opioid receptor

agonistCauses hallucinogenic-like, depression-like and anxiety-like statesNBOMeMost 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

Slide24

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

Slide25

Novel Psychoactive Substances

Continued

Benzofurans

and

Benzodifurans

Ring

substituded

amphetaminesStructurally related to MDMAEffects related to MDMA but more intenseExamples: 6-APB and 5-APBADE: nausea, sympathomimetic stimulation and agitation

Also known as the “fly” drugs (

bromo

-dragon fly, 2C-B-fly)Paranoia, agitation, tachycardia and hyperthermiaPiperazinesFound 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

Slide26

Novel Psychoactive Substances

Continued

Aminoindanes

Examples: MDAI and 5-IAI

Less neurotoxic than MDMA

Pipradrols

/

Piperidines“Ivory Wave”: contains 2-DPMP or D2PMSimilar to methylphenidateLong-lasting clinical toxicity:

sympthomimetic

stimulation, hypertension, agitation, hallucinations and insomnia

TryptaminesNatural 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

Slide27

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

Slide28

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 supportiveHeart rate, blood pressure and body temperatureHypertension 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

Slide29

Novel Psychoactive Substance

Treatment Continued

Consider

Naloxone administration

Physical cooling and relaxation may be needed in severe hyperthermia

cases

Behavioral therapies

Yet to be testedOnce patient is in recovery, a thorough assessment should occurTrace the history of the elicit substance

Pompei

P, et al. The “Legal Highs” of Novel Drugs of Abuse. J Drug Abuse. 2015, 2:2

Slide30

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 spasmsEffects influence by: dose, tolerance and presence of active metabolitesTreatmentIdentify the specific drug, dose and formulation

Identify co-exposures

Administration of Naloxone

Slide31

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 orallyIntravenous: effect seen within

2 minutes

Intramuscular: effect seen within 5 minutesDose: 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.

Slide32

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

Slide33

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

Slide34

Naloxone Access and Good Samaritan Laws

https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf

Slide35

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/TPAs-Naloxone-Standing-Order-Now-Available.htm

. November 2016

Slide36

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 SprayAny other opioid antagonist formulation permitted under the lawMay 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/TPAs-Naloxone-Standing-Order-Now-Available.htm

. November 2016

Slide37

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:

W

hen a pharmacist should or should not dispense

How to work with the patient in selecting which opioid antagonist to dispense

When to administerStanding 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/TPAs-Naloxone-Standing-Order-Now-Available.htm

. November 2016

Slide38

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

Slide39

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

Slide40

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 2011Schedule I controlled substance in the USSubject to annual aggregate manufacturing quotas

In 2014 the quota was 5 grams

Entirely user made and distributed

Regulated: codeine and hydrochloric acidUnregulated: gasoline, paint thinner, iodine and red phosphorous (from matchstick heads)

Alves EA, et al.

Forensic

Sci

Int.

2015 Apr; 249: 207-213.

Slide41

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.

Slide42

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.

Slide43

Krokodil

Haskin A, Kim N,

Aguh

C.

JAAD

Case Rep.

2016 Mar; 2(2): 174-176

Slide44

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.

Slide45

Questions???

Slide46

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-Now-Available.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