Recreational Drugs

Friedman RA. The Changing Face of Teenage Drug Abuse—The Trend toward Prescription Drugs.
New Eng J Med 2006;534:1448-50.

Highlight: This article in the Perspective section of NEJM highlights the growing problem of diversion and use of prescription drugs by teenagers.

Levine DA. “Pharming”: the abuse of prescriptions and over-the-counter drugs in teens.
Current Opinion in Pediatrics 2007;19:270-4.

Highlight: This is a review article that discusses the epidemiology of drug abuse in adolescents, particularly dextromethorphan and over-the-counter prescription drug abuse.

Boyer EW. Dextromethorphan Abuse. Pediatric Emergency Care 2004;20:858-63.

Highlight: A good overview of dextromethorphan, its history, epidemiology, pharmacology, and clinical effects.

Tennessee Poison Center and the American Association of Poison Control Centers partner with other organizations to protect the nation’s public health in terms of surveillance. One such partner is the National Drug Early Warning System (NDEWS). NDEWS monitors emerging drug use trends to enable health experts, researchers, and concerned citizens across the country to respond quickly to potential outbreaks of illicit drugs such as heroin and to identify increased use of designer synthetic compounds.

The NDEWS website is http://www.ndews.org.

INHALANTS ARE POISONS

FACT: Tennessee ranks 7th in the United States for inhalant abuse.

FACT: By the 8th grade, one in five young people has used an inhalant to get high; leading to risk of brain damage or death.

What Is Inhalant Abuse?

Inhalant abuse is the deliberate inhalation or sniffing of common products found in homes and schools to obtain a "high".

Inhalant abuse can kill suddenly, and it can kill those who sniff for the first time. Every year, young people die of inhalant abuse. Hundreds also suffer severe consequences, including permanent brain damage, loss of muscle control and destruction of the heart, blood, kidney, liver and bone marrow.

Today more than 1,000 different products are commonly abused. Many youth say that they begin sniffing when they're in grade school. They start because they feel those substances can't hurt them, because of peer pressure, or because of low self-esteem. Once hooked, these victims find it a tough habit to break.

What Products Are Abused?

Ordinary household products, which can be safely used for legitimate purposes, are poisons in the hands of an inhalant abuser. The following categories of products are reported abused: glues/adhesives, nail polish remover, marking pens, paint thinner, spray paint, lighter fluid, gasoline, propane gas, typewriter fluid, household cleaners, cooking sprays, deodorants, fabric protectors, whipping cream aerosols, and air conditioning agents.

How Can You Tell If Someone Is an Inhalant Abuser?

If someone is an inhalant abuser, some or all of these symptoms may be evident:

• Unusual breath odor or chemical odor on clothing
• Slurred or disoriented speech
• Drunk, dazed, or dizzy appearance
• Signs of paint or other products where they wouldn't normally be, such as on the face or fingers
• Red or runny eyes or nose
• Chronic inhalant abusers may exhibit such symptoms as anxiety, excitability, irritability or restlessness

What Can You Do To Prevent Inhalant Abuse?

One of the most important steps you can take is to talk with youth about not experimenting even a first time with inhalants. In addition, talk with teachers, guidance counselors and coaches.

Education should start at a young age. Inhalant abuse often begins in elementary school and can lead to further drug abuse, lifelong health problems or even death.

By discussing this problem openly and stressing the devastating consequences of inhalant abuse, tragedies can be prevented.

An adult training program, Inhalant Abuse: What You Should Know, is available at www.InhalantAbuseTraining.org. This program was developed by the New England Inhalant Abuse Prevention Coalition and the Massachusetts Northeast Regional Center for Healthy Communities.  

If you have a question about inhalant abuse or if someone has been poisoned by inhalants, call Tennessee Poison Center at 1-800-222-1222.

Synthetic Drugs – Dangerous and Deadly

One type is marketed as “synthetic marijuana.” The other is advertised as “fake cocaine” or “fake meth.” Both are marketed as legal equivalents to illegal drugs. But both cause alarming side effects that are generating a slew of calls to poison centers and spurring concern among doctors across the U.S.

The synthetic marijuana products sell for between $30 and $40 per 3-gram bag, in packages labeled as incense or potpourri and marketed under brand names like “Spice,” “K2,” “Genie,” “Yucatan Fire,” “Sence,” “Smoke,” “Skunk” and “Zohai.”

Poison centers receive calls about products marketed as “bath salts” sold both on the Internet as well as in gas stations and head shops. Packaging is usually a plastic bag filled with a white granular powder. The products are known as “Red Dove,” “Blue Silk,” “Zoom,” “Bloom,” “Cloud 9,” “Ocean Snow,” “Lunar Wave,” “Vanilla Sky,” “Ivory Wave,” “White Lightning,” “Scarface” and “Hurricane Charlie.”

They produce increased heart rate, increased blood pressure, agitation, hallucinations, extreme paranoia and delusions.

In September 2011, the U.S. Drug Enforcement Administration issued a ban of the chemicals used to make these dangerous drugs.

Experts at Tennessee Poison Center want you to be aware of the dangers of these products. Here are a few tips on what they are and the dangers surrounding them:

• Parents of teens should be on the lookout for such products in their children’s bedrooms and backpacks. Be particularly skeptical of products labeled “incense” or “bath salts.”
• Be aware of the signs and symptoms of drug use in loved ones: paranoia, changes in personality, agitation and anxiety are among the symptoms reported by users of these substances.
• Talk with family members about the dangers of these products. Don’t be fooled by the ready availability and legal status of new “designer drugs.” These products are not a “safe” or harmless alternative to other illicit drugs of abuse. Many can cause hallucinations and agitation that poison center experts say represent the opposite of a “mellow high.” In the case of bath salts, for example, poison center officials report instances of severe paranoia that has caused users to harm themselves and others.
• Keep Tennessee Poison Center’s number in your phone: 1-800-222-1222.
  Remember - You can call Tennessee Poison Center to ask about these substances even if you have not been exposed to them. Tennessee Poison Center is open 24 hours a day, seven days a week. Calls are fast, free, and confidential.

What’s in Bath Salts?

“Bath Salts” is the most common term referring to a set of synthetic drugs also sold as “Plant Food.” Labeled “not for human consumption,” the active ingredient may be one of several synthetic drugs similar to natural cathinone psychostimulants found in the khat plant:

• Methylenedioxypyrovalerone (MDPV)
• Fluoromethcathinone                     
• Methylenedioxymethcathinone (methylone)
• Methoxymethcathinone
• Methylmethcathinone (Mephedrone)
• Dimethlyamylamine (DMAA)
• Diphenylmethylpiperidine (2DPMP)

The crystals or capsules may contain the anesthetic lidocaine. Bath salts are known by various brand names: Ivory Wave, Vanilla Sky, Zoom2, Pixie Dust, Sextacy, Ocean Burst, Purple Rain, Hurricane Charlie and many more.

Why do people inhale and ingest bath salts?

The products were rumored to be legal substitutes for amphetamine or cocaine. Until recently, the ingredients were legal and could be purchased at smoke shops or convenience stores.

How popular is the use of these products?

Throughout the US, Poison Centers have been tracking calls about users hospitalized. In 2011, Tennessee Poison Center received 208 calls regarding “bath salts”.

What happens to people who snort or smoke bath salts?

The nervous system is stimulated; creating a burst of energy along with high blood pressure, fast heart rate, increased alertness, anxiety and muscle cramps. There are frightening delusions, hallucinations, psychosis and paranoia. There are multiple accounts of people thinking that monsters, policemen or helicopters are chasing them. This has resulted in combativeness, assaults and suicide attempts. Deaths potentially related to these products are being investigated.

For more information or for medical assistance after contact with bath salts, call Tennessee Poison Center at 1-800-222-1222.

Toxicology Question of the Week

February 25, 2019

What are the differences in the pharmacological effects and blood levels for THC and CBD when administered orally vs. inhalation?

There is limited information available regarding the pharmacokinetics and pharmacodynamics for either tetrahydrocannabinol (THC) and cannabidiol (CBD) in humans. Only a few studies have been published so far, and most of them were conducted in healthy adult volunteers with very small sample sizes. Additionally, frequent cannabis smokers were included in some of the studies, not all included both males and females, and none of the studies addressed the subjects’ fat content as a factor to account for the cannabinoid’s highly lipophilic nature. Overall, there is considerable variability between studies and further research is warranted. Below is a summary of the available information.

Inhalation of cannabinoids exhibit similar pharmacokinetics to those administered intravenously. Peak concentrations are attained within 10 minutes and are higher in comparison to ingestion. Bioavailability after inhalation ranges from 10-35% with the variability attributed to the number, duration, and interval of puffs, breath hold time, inhalation volume, inhalational device, size of inhaled particles, and site of deposition within the lungs. The absorption of vaporized and smoked cannabinoids are comparable.

Cannabinoids have poor oral bioavailability (estimated to be as low as 6%) due to their high lipophilicity and extensive first-pass hepatic metabolism (i.e. liver metabolizes most of it).  Peak concentrations are delayed by 2-4 hours and are much lower in comparison to inhalation. Increased peak concentrations and total absorption, but not time to peak concentration, are seen when cannabinoids are administered with food or in a fed state.

The psychoactive effects from ingestion and inhalation of THC are comparable. However, since the legalization of marijuana, edible products are responsible for the majority of emergency department visits due to cannabinoid intoxication. This is likely due to the failure of users to appreciate the delayed effects of ingestion compared to inhalation. Typically, a tenth of a product (cookie, packet of gummy bears, etc.) is recommended for intoxication. Because many find it difficult to eat a tenth of a cookie, unintentional overdose is common. These patients usually present with severe anxiety, panic attacks, intractable vomiting, or other nonspecific symptoms precipitated by marijuana use.

CBD is without euphoriant properties, and exerts antipsychotic, anxiolytic, antiepileptic, and anti-inflammatory effects. Unfortunately, we could not find any studies comparing the effects of orally administered CBD to inhalation. The effects are likely to be comparable to other cannabinoids in the respect that inhalation will produce a more rapid onset with a shorter duration while ingestion would produce a more consistent plasma-time profile suitable for symptomatic relief over a longer period.

This question prepared by: Justin Loden, PharmD, CSPI, DABAT

References

1. Cherniakov I, Izgelov D, Barasch D, et al. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. J Control Release. 2017 Nov; 266:1-7.
2. Liu Z, Martin JH. Gaps in predicting clinical doses for cannabinoids therapy: overview of issues for pharmacokinetics and pharmacodynamics modelling. Br J Clin Pharmacol. 2018 Nov; 84(11):2483-7.
3. Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018 Nov; 84(11):2477-82.
4. Millar SA, Stone NL, Yates AS, et al. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018 Nov 26; 9:1365.
5. Monte AA, Zane RD, Heard KJ. The implications of marijuana legalization in Colorado. JAMA. 2015 Jan 20; 313(3):241-2.
6. Newmeyer MN, Swortwood MJ, Barnes AJ, et al. Free and glucuronide whole blood cannabinoids’ pharmacokinetics after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis users: identification of recent cannabis intake. Clin Chem. 2016 Dec; 62(12):1579-92.

Thanks to the reader (in South Dakota!!-hope you have dug out of the snow by now) for this great question. 

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Executive Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

February 4, 2019

Does CBD oil cause a false positive for THC on UDS?

I was asked the above question by a health care provider.  I immediately sent it to the expert, Jennifer Colby PhD, Chief of the analytic tox lab.  This is what she said:

CBD oil presents a interesting issue.  If the CDB oil was legally acquired in TN it should have a max THC content of 0.3%.  If it was acquired elsewhere (or if it came from a manufacturer overseas with poor quality control) all bets are off.  If a patient is using locally sourced oil from a reputable manufacturer, I would be surprised if the low-level contamination was enough to cause a positive screen.  As far as I know there are no regulations about the concentration of cannabinol in the CBD oil, so it could be there are relatively high amounts, enough to cause a positive screen.  However, I have not tested that, and I am not aware that anyone else has. 

Question prepared by Jennifer Colby PhD, Associate Director of Clinical Chemistry, VUMC

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Executive Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

April 4, 2018

Clinical picture of Phenibut toxicity is similar to that of baclofen.  ds

Phenibut: Is It a Smart Drug To Take? 

The Tennessee Poison Center has received several calls over the past few weeks from clinicians about a drug named phenibut.

WHAT IS IT?

Phenibut (beta-phenyl-gamma-aminobutyric acid), AKA: Fenibut, Noofen, Phenigam, party powder. Is a neuropsychotropic drug that was first discovered and introduced into clinical practice in Russia in the 1960’s. Soviet cosmonauts use it for its mentally stimulating and calming effects! Phenibut is labeled as a nootropic “smart drug”. It is unregulated by the Food and Drug Administration. It can be purchased in the United States via the Internet as a dietary supplement for anxiety, sedation, stress reduction, insomnia, mood enhancement and cognition enhancement.

HOW DOES IT WORK?

It acts as a GABA‐mimetic, primarily at GABA_B and, to some extent, at GABA_A receptors. It also stimulates dopamine receptors and antagonizes β‐phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p‐Cl‐derivative of phenibut.

PHENIBUT                                                       BACLOFEN

SIDE EFFECTS:

Are generally linked to its central nervous system depressant effects, such as CNS and respiratory depression.

These include gastrointestinal symptoms (nausea, vomiting) central nervous system symptoms (insomnia, agitation, confusion, euphoria, depression, hallucinations)

TREATMENT:

In the changing pace of the designer drug market, please call the Tennessee Poison Center 1-800-222-122 for the latest updates on treatment modalities. Treatment includes good supportive care and benzodiazepines for agitation.

CONCLUSION:

Caveat Emptor! Since the advent of the Internet, many substances including illegal ones have found their way to consumers across the USA. The reported adverse effects of phenibut are just the tip of an iceberg of an unregulated buy online designer drug market with no standards of quality assurance.

REFEREENCES:

Phenibut (β‐Phenyl‐GABA): A Tranquilizer and Nootropic Drug

Izyaslav Lapin

Micromedex/Poisondex Heath Series by Truven Health Analytics

The Vaults of Erowid

www.bing.com/images/search

This Question was prepared by: Nena Bowman, PharmD, DABAT, Managing Director of Tennessee Poison Center

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

March 21, 2018

What causes false positives or false negatives on the Urine Drug Screen (UDS)?

We frequently get questions regarding the meaning of false positives and negatives on the urine drug screen.  I’ve asked a real expert to address them.  ds

On false positives:

In a false positive urine drug test, the drug of interest is not present in the sample.  False positives can be due to unrelated cross-reacting compounds (e.g. sulfamethoxazole/trimethoprim can cause a false positive buprenorphine screen) or due to the presence of related compounds that are not confirmed (some designer amphetamines will cause a positive amphetamines screen but will not be confirmed).  Because of the potential for false positives laboratories will report screening results as “presumptive” positive.  Until the laboratory has reported confirmatory test results, presumptive positive screens should be regarded as preliminary and interpreted with caution.

On false negatives:

In a false negative urine drug test, the drug of interest is present in the sample but is not detected.  False negatives can occur when the concentration of drug is below the threshold for positivity (also called the cutoff).  False negatives can also occur due to varying cross-reactivity to drugs that belong to one class.  For example, benzodiazepines assays are prone to false negatives for lorazepam and clonazepam because antibodies used in the test have lower sensitivity for these drugs compared to diazepam and alprazolam.

Below is a summary of known false positives and false negatives for VUMC urine drug screens.  This list is subject to change and the laboratory is always available to assist with interpretations (call 5-LABS).

** Synthetic opioids like tramadol, tapentadol, and fentanyl are not detected by this assay.

-- False negative/positive not frequently observed using VUMC’s test.

This Question was prepared by: Jen Colby PhD, Chief Toxicology Lab; Associate Director of Clinical Chemistry VUMC.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

                     Toxicology Question of the Week

                                                                 March 6, 2018

What can the DEA tell you about changing patterns in use/trafficking of Drugs of Abuse?

Last week I attended the Midyear Meeting for Poison Centers, a meeting that addresses primarily issues of funding/evaluation/functioning of the poison center.  Two DEA agents gave an update on current Drug of Abuse use/trafficking, I’m sharing my notes with you.  I thought some of the new patterns, as well as the reason for them, was quite interesting.  ds

• Much of the fentanyl is coming from China and Mexico.  It is then combined with heroin in a pill press.  The resultant tablet resembles oxycodone 30 mg tabs, but is much cheaper than actual oxycodone.

• Cocaine trafficking is increasing from Columbia.  The Columbian government made a peace treaty with the rebels and part of the deal was that government would stop eradicating the coca plants.  (I wish the rebel who negotiated that deal would throw down some pointers or teach a class on the art of the deal) Cocaine exports have increased to the point that traffic is similar to that of the cartel days.  One kg of cocaine will get more money in Europe or Panasia than in the US, so there is currently greater trafficking to other countries than to the US.  A 4-5 year lag occurs from the time of increased production to increased misuse, so more cocaine overdoses are on their way.

• Methamphetamine is now produced primarily in Mexico rather than locally due to the difficulty obtaining pseudoephedrine.  The price has dropped so purity is increasing.  Purity from 2011 to 2016 increased 90%.

• DEA Red Flags

In a survey of > 6000 communities, the following were the greatest drug threats:

1)heroin  2)methamphetamine  3)CBD   4)fentanyl   5)marijuana  6)cocaine

• Much CBD ((cannabidiol)active cannabinoind in cannabis-not psychoactive) is being produced locally and sold over the internet.

• Marijuana is a Schedule 1 Controlled substance ( federal ), a classification that indicates there is no medically accepted use. 70% of Schedule 1 research is investigating marijuana.  Currently there is no evidence that it alleviates chronic pain or lessens opiate use.

• Kratom contains active opioid constituents.  In animal studies it is similar to morphine and is being used as a substitute for opioids.  There are many reports of abuse, dependence, and negative outcomes from it use.  It is sold as dried leaves, powder, capsules and tablets.  There have been multiple seizures by the FDA.  Many designer products contain Kratom.

• Total number of prescriptions written for controlled substances has decreased in the US.  Some states limit the number of days for which controlled substances can be prescribed. 

• National prescription take back day is April 28.  It occurs twice a year, April and October. One of the keys in determining success is the number of law enforcement officers involved at the local level.   Last October, 456 tons of pills were taken back.  Over the past 8 years 4500 tons have been procured.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

February 5, 2018

What is the latest update on treatment of opiate use disorder?

Below is a commentary by Nora Volkow MD that was recently published in the Lancet.  Dr. Volkow is Director of the National Institute on Drug Abuse at NIH.  She pioneered the use of brain imaging to investigate the effects of drugs in the human brain and has demonstrated that drug addiction is a brain disease.  She has published over 600 scientific articles and edited three books. Her commentary on the treatment of opiate addiction is insightful.  ds

www.thelancet.com Vol 391 January 27, 2018 285

For the past two decades, the USA has been in the
throes of an opioid crisis marked by a rising number of
deaths; in 2016, opioids were responsible for most of
the nation’s estimated 64 000 fatal drug overdoses.1 The
problem began with overprescribing of opioid analgesics
in the 1990s, which exposed pain patients to the risks
of addiction and produced large surpluses of pain pills
that were diverted for misuse by the larger community.
Additionally, the escalating numbers of opioidaddicted
Americans led to increased HIV and hepatitis C
transmission among people who misuse these drugs by
injecting them2 and increased numbers of infants born
dependent on opioids as a result of the mother’s opioid
use (neonatal abstinence syndrome).3
The opioid crisis has been a moving target; while it
began with the misuse of prescription opioids, this then
opened the door to an increase in heroin use.4 A decade
ago, most people who misused opioids in the USA had
initiated with prescription drugs, but now heroin is
reported as the opioid of initiation more often than the
most commonly prescribed opioids, oxycodone and
hydrocodone.5 There has also been an influx of new,
more potent synthetic opioids such as fentanyl—often
used to adulterate or replace heroin because it is cheaper
to produce and easier to import—that has increased
the danger for users and perpetuated the trend towards
increasing opioid overdose deaths.6 US Government
authorities and the medical community are addressing
the problem in a range of ways. In March, 2016, the
US Centers for Disease Control and Prevention (CDC)
revised its guidelines for opioid prescribing for chronic
non-cancer pain, recommending alternative approaches
in pain management and limitations on the dosing
and duration of opioids when they are called for.7 Law
enforcement and diplomatic efforts are being made
to stem the influx of synthetic opioids, which mostly
originate in Chinese laboratories.8 And to save the lives
of people who overdose on opioids, most US states
have taken steps to increase the availability of the opioid
antagonist naloxone to police, emergency medical
personnel, and opioid users themselves.9 This safe and
easily used medication can quickly reverse the effects of an
opioid overdose and restore breathing if it is administered
in time; and communities that have distributed naloxone
to opioid users, their families, or potential bystanders have
seen reductions in overdose deaths.9 Naloxone is now
available in an easy-to-administer nasal spray, although
multiple administrations are sometimes necessary when
overdoses involve fentanyl or other potent synthetics.
Researchers are working to develop more potent and
longer-lasting opioid antagonists to counter the fentanyl
threat.

Addiction treatment is equally important in reducing
deaths and infectious disease transmission, although
historically in the USA such treatment has been hard to
access, is not covered by most insurances, and is of variable
quality.10 Health-care reform efforts during the past
decade have begun to increase access to evidence-based
treatment for substance use disorders and to integrate
that treatment into the larger health-care system.11
Medications are the gold standard of treatment for opioid
use disorder.12 There are currently three medications
approved by the US Food and Drug Administration (FDA),
all of which target the μ-opioid receptor. Methadone and
buprenorphine have agonist effects, addressing craving
and withdrawal symptoms without producing euphoria
and are used for long-term maintenance therapy.12 By
contrast, naltrexone is an antagonist at the receptor and
prevents illicit opioids from having an effect.12
In the USA, medications are required to be given in
conjunction with some form of counselling or behavioural
therapy, called medication-assisted treatment (MAT),
but there remains a vast gap between those who
would benefit from MAT and those who receive it.13
This gap reflects both lack of treatment capacity and
an entrenched stigma against use of medications for
opioid use disorder arising from the belief that these
medications simply substitute one addiction for another.
This belief, a holdover from early models of recovery that
emphasised complete abstinence from all medications,
reflects a misunderstanding of the pharmacological and
therapeutic effects of these drugs. When an opioid user
is treated with methadone or buprenorphine, the doses
used do not produce euphoria or trigger the conditioned
responses that generate craving.12 These medications
reduce withdrawal symptoms, improve mood, and help
restore physiological balance—allowing the patient’s
brain to heal while he or she works towards recovery.12
Methadone, the first medication developed for
opioid use disorder, is less expensive than the other
Medications for opioid use disorder: bridging the gap in care.

Published Online
November 14, 2017
http://dx.doi.org/10.1016/
S0140-6736(17)32893-3
See Comment page 283
See Articles page 309

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

                         Toxicology Question of the Week

February 1, 2018

           What is Shock Dope?         

Reports of wasp spray abuse, or “shock dope” (“Synthetic Drug”, 2018) have recently surfaced in Tennessee, or re- emerged as the practice has been around for over a decade.  It involves a simple process (although dangerous as you can turn your vehicle into a flamethrower). The recipe includes an automotive (SLI) battery, can of insecticide (pyrethroid based), some chicken wire, or window screen. The wire is attached to the battery with jumper cables, or directly to the battery, in order to deliver a current, then aluminum foil is placed under it. The wire is sprayed with insecticide, which will crystallize. The battery is then disconnected, and the crystals are tapped off the wire which equals what is a fresh batch of cheap pyrethroid. In reality, it is often mixed with meth as distributors (“dealers”) can pass it off as a cheap substitute for the pure form of methamphetamine. The crystals are injected, snorted, or smoked.
 

The theory behind the insecticide is there is no narcotic component (in the absence of a combination illegal recreational substance), but your neurological functions are altered e.g. “loopy”.  Pyrethroids are known to cause hyperexcitation by targeting sodium channels which are kept open for unusually long periods of time, which may account for the rush with exposure. Mixed with meth, the effects are more pronounced. 

The toxicity associated with pyrethroids include:    headache, upper and lower airway irritation, chest pain.  Parenteral use can cause a local erythema, cellulitis, and vasculitis.  Chronic use can lead to personality changes.

The care is supportive, regardless of the route of exposure: treat the symptoms.

Implications for practice

The main challenge is keeping up on what to watch for. Every time we turn around, there is a new method of substance abuse.  Of a point of note, reports document these substances as being more attractive, especially to teens and young adults as they are “legal” and there is easy access.

Do not be surprised if you are asked for an id to buy bug spray.

KSN TV, Kansas City. Synthetic Drug a problem for Kansas [video file], (11/2018)

KXRB, Sioux Falls. Parents Beware of Wasp Spray[video file], Aug. 9, 2017, retrieved from: kxrb.com/parents-beware-of-wasp-spray-drug/

Pravesh,S. Manning,S, et. al. ( 2014). Pyrethroid as a substance of abuse.  Case Reports in Psychiatry.2014, Article ID 169294,

pp. 1-3

WTVF, Lawrenceburg, TN. Man Found Naked In Tree After Doing 'Wasp Spray Dope' [video file](Jan.4, 2018), retrieved from:   https://www.newschannel5.com/news/man-found-naked-in-tree-after-doing-wasp-spray-dope

This Question was prepared by Jennifer C. Anderson, MSN, RN, CCRN, CPNP

Tennessee Poison Center

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

April 10, 2017

Why Would Antiretroviral Drugs Be Abused?

     Over the last five years, antiretroviral (ARV) medications have gained popularity as recreational drugs. This misuse began in South Africa, which has the largest HIV/AIDS population in the world. Unfortunately, the abuse of this product has reached the United States (US) with reported use in Florida. Clubgoers in the Miami areas are using this very addictive drug and may not realize what the ingredients are as it is being sold as “cocktails”.  Grelotti, et al. (2014) interviewed HIV-infected people in this area and the users reported abusing ritonavir with 3,4-methylenedioxy-methamphetamine (MDMA) and methamphetamine for the enhanced and prolonged effects of the drug.  In addition, they use efavirenz alone for the euphoric effects- it does not require combined use with any illicit drugs.  

   Efavirenz (Stocrin) is the most popular ARV.  Users crush the pill into a powder and make a mixture using rat poison (strychnine), ARV’s, detergent and illicit drugs (heroin, marijuana, MDMA, phencyclidine (PCP) or cocaine).  The brown mixture has a vinegar smell and is usually sold in little plastic wrappers.  The drug is being smoked for the hallucinogenic effects and is called Whoonga, Wunga and Nyaopa.  Sadly, it is being utilized by people as young as 14 years old. 

     The most common adverse effect (52% of users) is central nervous system (CNS)/psychiatric disturbances. The drugs interaction with substrate and inhibitor versus inducer creates the preference for the most desireable ARV’s.  Non-nucleoside reverse transcriptase inhibitors (NNRTI’s)- nevirapine, efavirenz, protease inhibitors (PI’s)- indinavir and nucleotide reverse transcriptase inhibitors (NRTI’s)- zidobuvine, stavudine, lamivudine consistently penetrate into the cerebrospinal fluid (CSF).  Using these combinations will enhance the desired effects.  Grelotti, et al. (2014) has a great chart with the effects listed below: 

     Whoonga is number 2 on the list for homemade street drugs that are most devastating.  The feelings one experiences from consuming the drug only lasts about 2-4 hours.  It wears off in 6-24 hours and the user has terrible withdrawal signs and symptoms.  The unbearable abdominal pain, anxiety, backache, muscle cramps, depression, nausea and vomiting make the drug so addictive.  Addicts consume approximately 5 baggies of Whoonga daily to remain free from withdrawal.  Studies show people intentionally becoming infected with HIV/AIDS to obtain the ARV’s for free.  It is no surprise that Whoonga users have taken it to the next level since they are not concerned about becoming infected with HIV/AIDS. They are doing a “bluetooth” method.  This consists of a user injecting himself/herself with Whoonga to get high.  Next, they leave the needle in place and withdraw some of their blood.  Then, the blood is injected into someone else so they can also experience the high as well.  Below is a 1 minute you-tube video on Whoonga/Nyaopa/Wunga.

https://youtu.be/PVtx8oDILws

References:

Davis, G. P., Surratt, H. L., Levin, F. R., & Blanco, C. (2013, September 17). Antiretroviral medication: an emerging category of prescription drug misuse. Retrieved December 28, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956727/

Grelotti, D. J., Closson, E. F., Smit, J. A., Mabude, Z., Matthews, L. T., Safren, S. A., . . . Mimiaga, M. J. (2015, March). Whoonga: Potential recreational use of HIV antiretroviral medication in South Africa. Retrieved December 28, 2016, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926908/

H. (2015, December 20). Top 10 Deadliest Street Drugs & Their Effects. Retrieved December 28, 2016, from https://www.youtube.com/watch?v=1Is6CAvnqwg

Knox, R. (2012, December 18). Dangers of 'Whoonga': Abuse of AIDS Drugs Stokes Resistance. Retrieved December 28, 2016, from http://www.npr.org/sections/health-shots/2012/12/18/167523601/dangers-of-whoonga-abuse-of-aids-drugs-stokes-resistance

Nyaope / Whoonga. (2016, December 07). Retrieved March 20, 2017, from http://www.mobieg.co.za/articles/addiction/types-of-drugs/nyaope-whoong…

Software Informer - Micromedex Healthcare Series Browser ... (2016). Retrieved March 24, 2016, from http://micromedex-healthcare-series-browser.software.informer.com/

10 Most Devastating Homemade Street Drugs. (n.d.). Retrieved March 20, 2017, from http://www.bestcounselingdegrees.com/10-most-devastating-homemade-street-drugs/

This Question prepared by: Renee Miller, DNPc, MSN, RN, CSPI

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org , Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Toxicology Question of the Week

March 9, 2017

What is “pink”?

2016  Headlines:

Park City police have confirmed that two 13-year-old boys who were found dead in September overdosed on the synthetic opioid known as "pink." (Nov. 3, 2016, Fox 13, Salt Lake City)

Overdose deaths suggest emergence of deadly synthetic opioid 'pink' in Alaska. (Nov. 2016, Alaska News)

Pink: Stronger than heroin, but legal in most states; NH has already seen first death

(Oct, 2016, New Hampshire Union Leader)

Another Powerful Painkiller Found in Prince's System: U-47700 ( July,2016,5 ABC News, St. Paul, MN)  ______________________________________________________________________________

There has been an emergence of the synthetic opioid, U-47700, otherwise known as “pink”, “pinky”, or “U4”. Why the name pink?   Well, it’s a street drug, so you have to have a catchy title.  Seriously, though, the powder has a very light pink tinge.

This substance has been implicated in multiple deaths over the last two years.  The drug was manufactured in the 1970’s by Upjohn ( the “U” in the description). It was being utilized for research as a possible alternative to morphine. It was never tested on humans and, needless to say, did not receive FDA approval, and thus was not marketed for sale.  It is reported to be approximately 7.5 times more potent than morphine and stronger than heroin (Szmuszkovicz,1978).  However, “pink” has now migrated to foreign drug manufacturers.

 “Pink” can be combined with heroin or any number of drugs.  It can be inhaled, injected, or pressed into pills that are almost indistinguishable from traditional medications. As with an opiate, severe exposure can lead to severe respiratory depression (Helander, 2017).   According to the DEA, this substance, as many others, are difficult to regulate as the can be ordered online from foreign labs, specifically citing China.

As of Nov. 14, 2016, he USDEA placed U-47700 into Schedule 1 of the Controlled Substances Act. 

This novel synthetic opiate use is increasing exponentially in the United States.   Due to the “newness” of the substance, the DEA is in early stages of investigation.  Healthcare providers need to raise awareness not only to customers, but to colleagues as well.  The DEA struggles to keep up with new compounds.  As soon as one is banned, another stronger, more potent, more deadly takes its place.

References:

Helander,A., Bäckberg, M.(2017). "New psychoactive substances (NPS) – the hydra monster of recreational drugs".

      Clinical Toxicology, 55(1) 1–3.

https://federalregister.gov/d/2016-27357

Micromedex(2015).

Szmuszkovicz,J. (4 July 1978). Patent US4098904 - Analgesic N-(2-aminocycloaliphatic)benzamides.

This Question prepared by: Jennifer Anderson, MSN, RN, CCRN, CPNP, SPI

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

The Question of the Week is available on our website: www.tnpoisoncenter.org

Why the Agony about Ecstasy?

One percent of the population uses Ecstasy once a month. Twenty four percent of college students use this drug regularly. The majority of 16 year-olds believes Ecstasy (Adam, XTC, M&M, E) use is “safe”.

Ecstasy (MDMA-3, 4-methylenedioxymethamphetamine) is one of the “Designer Drugs” of the 1980s.  The term “Designer Drug” was first used by a Californian pharmacologist to describe the private synthesis of drugs differing from the parent compound which rendered them immune from the DEA.  The loophole was that until a drug was isolated, studied, and scheduled, no laws could apply to it.  The Controlled Substance Analogue Enforcement Act of 1985 categorized analogs of controlled substances as Schedule I and all the laws of Schedule I subsequently applied to them.

MDMA has the same basic chemical structure as an endogenous catecholamine (as do ephedrine and amphetamine).  It alters mood and perception, increases energy and empathy.  It is one of a group of drugs called enactogens (meaning to touch within) and is it initiates euphoria, “inner peace” and a desire to socialize. MDMA has all the right characteristics for a dance drug and is popular at raves (dances).  The aftermath of Ecstasy is a day of drowsiness, myalgia, fatigue, and depression- frequently called “Terrible Tuesday”.

Serotonergic neurons lie next to midline nuclei of the brainstem and project to virtually all areas of the brain.  Serotonin effects mood, personality, affect, appetite, motor function, temperature regulation, sexual activity, pain perception, and sleep. Serotonin is also produced in the enterochromaffin cells of the intestine and, when released, contributes to peristalsis.  Platelets take up serotonin and it is released to interact with other platelets and vascular smooth muscle.

The main mechanism of action of MDMA is release of serotonin from serotonergic neurons which causes depletion of central serotonin stores. The number of serotonin reuptake transporters is also decreased.  The drug also causes irreversible inhibition of the enzyme tryptophan hydroxylase (which is rate limiting step in synthesis of serotonin).  The enzyme is inhibited up to 2 weeks as the enzyme must be resynthesized.   

Tryptophan→/→/→/→5HTP→→→→  5HT (serotonin)               

                 Tryptophan

                 hydroxylase

                (Inhibited by MDMA)                                     ↓↓↓

                                                                                5-HIAA (urine)

5-hydroxyindoleacetic acid

Usual dose is 100 mg MDMA per tablet but tablets can vary from 50 mg to 250mg.  Onset of action is within 30 minutes and peak serum levels occur at 1-3 hours.  Toxic dose is extremely variable.

In overdose, this drug is similar to an amphetamine (or stimulant) overdose and heart rate, blood pressure and temperature are increased.  The person is diaphoretic, agitated, and may have muscular rigidity.  Hyperthermia can be severe and is frequently the cause of death. Rhabdomyolysis may occur.  Hyponetremia from SIADH production has been reported.  Treatment is supportive.  Hyperthermia should be addressed as soon as possible.  Dantrolene may be a consideration, although evidence is inconsistent. 

A major concern with MDMA is the long-term effects on cognition. One of the reasons that animal research was discontinued with this drug was that it caused neurodegeneration of CNS serotonin axons.  Once the axon degenerated, different patterns of recovery occurred in different areas of the brain i.e., some areas had no axonal regeneration and other areas had increased density of axonal regeneration.  The clinical implications of this axonal degeneration and recovery are unknown.

Memory loss and other cognitive deficits were seen in MDMA users even 6 months after abstinence.  PET studies of users are abnormal.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

Website: www.tnpoisoncenter.org

Question of the Week

February 7, 2017

Why did the DEA delay its ruling to ban Kratom?

http://www.medscape.com/viewarticle/874301?nlid=112393_745&src=WNL_mdplsfeat_170131_mscpedit_phar&uac=173893HV&spon=30&impID=1281987&faf=1

The above link submitted by Nena Bowman, PharmD, DABAT  Tennessee Poison Center

It is amazing what happens to the legislation of herbal preparations that are not subject to the same laws as drugs.  Popular opinion and politics certainly play a part.  Note that Tennessee was one of the first states to ban the sale of Kratom.  Good for us! /ds

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222

Question of the Week

January 31, 2017

What should I know about exposure to e-cigarettes?

E-cigarette use is increasing in both middle and high school students, according to the CDC. Up to 13% of high school students now report using e-cigarettes in the past 30 days, and increases in e-cigarette advertising is associated with increasing use in youth in the United States.

Typical Electronic Nicotine Delivery Systems (ENDS) devices include a battery, a heating element, and a cartridge which contains the e-liquid, which is usually comprised of nicotine, propylene glycol, and glycerin. Nicotine exposure can occur by ingestion, inhalation, transdermal absorption, and ocular exposure.

The CDC noted a significant increase in e-cigarette-related calls to poison centers from 2010-2014. 51% of these exposures were among children less than 5 years old.  The most common adverse effects noted during calls were vomiting, diarrhea, and eye irritation. However, nicotine ingestions in pediatric patients can be dangerous in large doses.  Noble et al recently reported a case of unintentional ingestion of 35 mg/kg of liquid nicotine in a 6-year-old female who developed seizures, obtundation, and fasciculations, requiring intubation and ICU admission.

Nicotine binds to nicotinic cholinergic receptors, initially causing sympathetic nervous system stimulation. In larger doses, there may be parasympathetic stimulation, followed by neuromuscular blockade. Clinically, nicotine ingestion causes dizziness, nausea, vomiting, pallor, and diaphoresis. In severe poisonings, confusion, agitation, lethargy, and seizures may be seen. Respiratory muscle weakness ultimately causes respiratory arrest and death.

Sources:

CDC: E-cigarette ads and youth. https://www.cdc.gov/vitalsigns/ecigarette-ads/index.html

Olsen, K. Poisoning & Drug Overdose, sixth edition (2012). Noble, et al. Unintentional Pediatric Ingestion of Electronic Cigarette Nicotine Refill Liquid Necessitating Intubation. Annals of Emergency Medicine 2017;69;1, 94-97.

This question prepared by: Elise Springer, MD Pediatric Emergency Medicine Fellow Vanderbilt University Medical Center

Question of the Week

February 17, 2016

Why do antipsychotic medications have street value?

Misuse/abuse of second-generation antipsychotics, particularly quetiapine and, less commonly, olanzapine is increasing due to increased prescribing and a dramatic rise in off-label use for insomnia and anxiety.

From 2005 to 2011, quetiapine-related Emergency Dept (ED) visits for misuse/abuse, suicide attempt, or adverse reactions increased 90%. The leading cause of quetiapine visits was misuse or abuse, defined as any nonmedical use, overmedication of a drug taken alone or in combination with other substances (including medication prescribed for another person). (1)

What are the potential reasons for abuse of second generation antipsychotics? (1 5). From a pharmacologic standpoint, serotonin, histamine, and α-adrenergic neurotransmitter systems play a role. At low doses, quetiapine primarily acts as a histamine (H1) antagonist and serotonin receptor antagonist (increasing synaptic serotonin). The sedating effects (H1 antagonism) and anxiolytic effects (α-blockade) are the likely drivers of misuse. The dopamine blocking effects (which would seem counterintuitive as drugs of abuse cause dopamine release) occur only in high doses (>300mg) (2).

Inpatient addiction center surveys reveal that the majority of patients using antipsychotics are male, polysubstance users, and obtained quetiapine from a physician (52%) or family/friends (48%). Reasons given for misuse included to recover from other substances (66.7%), enhance effects of other substances (25%), and to experiment (20.8%). (3) Other reasons include: self-medicate insomnia and anxiety, get drunk without the hangover, reduce the crash from stimulants such as cocaine, zone out, take the edge off, isolate themselves from prison surroundings, substitute for other drugs (jailhouse heroin), and to calm nervousness and anxiety after crack cocaine use. (1) Most (75%) reported the positive effect of feeling mellow. (4)

Quetiapine goes by various street names (quell, Susie Q, baby heroin, squirrel) (1) and has a street value of $3-8 per tablet (5). Misuse/abuse is not limited to PO use. Inhaling, intranasal use, and injecting tablets, sometimes in combination with drugs like cocaine (referred to as a Q-ball ) have been described. Waters and Joshi hypothesized that the substitution of quetiapine for heroin may mitigate the dysphoria associated with cocaine withdrawal and possibly provide a hallucinogenic effect (6).

The literature detailing with second generation antipsychotic abuse and misuse is increasing each year. Providers must be aware of the potential for diversion, misuse and abuse of these medications and should consider alternatives if prescribing for off-label use. This is especially important if prescribing to anyone with a history of substance abuse.

References

1. Mattson ME, Albright VA, Yoon J, Council CL. Emergency department visits involving misuse and abuse of the antipsychotic quetiapine: results from the Drug Abuse Warning Network (DAWN). Substance abuse: research and treatment. 2015;9:39.
2. Montebello ME, Brett J. Misuse and Associated Harms of Quetiapine and Other Atypical Antipsychotics. Current topics in behavioral neurosciences. 2015 Dec 23.
3. Bogart GT. Abuse of second-generation antipsychotics: What prescribers need to know. Current Psychiatry. 2011 May 1;10(5):77.
4. Malekshahi T, Tioleco N, Ahmed N, Campbell AN, Haller D. Misuse of atypical antipsychotics in conjunction with alcohol and other drugs of abuse. Journal of substance abuse treatment. 2015 Jan 31;48(1):8-12.
5. Fischer BA, Boggs DL. The role of antihistaminic effects in the misuse of quetiapine: a case report and review of the literature. Neuroscience & Biobehavioral Reviews. 2010 Mar 31;34(4):555-8.
6. Waters BM, Joshi KG. Intravenous quetiapine-cocaine use (" Q-ball"). The American Journal of Psychiatry. 2007 Jan;164(1):173.

This question prepared by: Rick Carlson, MD Clinical Fellow, Psychosomatic Medicine Department of Psychiatry (VUMC)

Question of the Week

April 6, 2015

What is the new synthetic drug 25I-NBOMe (N-Bomb)?

The recreational use of synthetic (designer) psychoactive substances with stimulant, euphoric, and/or hallucinogenic properties has risen dramatically in recent years. The illegal status of classic recreational substances (e.g. cocaine, ecstasy, cannabis, etc.) has encouraged users and suppliers to seek alternative options in order to evade current drug legislation. These substances are usually created by modification to the molecular structures of existing illicit compounds to produce similar subjective effects but offer the advantages of being technically legal, less expensive, readily available, likely undetectable by routine drug abuse screens, or having more desirable/potent pharmacological effects. The substances abused frequently change in response to legislative controls and market demands, and it is important for health care providers to remain up-to-date on the toxicological effects of these emerging agents.

25I-NBOMe is a representative of a new class of hallucinogens called 25X-NBOMe or simply NBOMe (pronounced N-Bomb). These compounds are research chemicals originally developed as high affinity ligands for use in mapping the distribution of serotonin receptors in the brain. NBOMe have virtually no history of human use prior to 2010 when they initially became available over the internet. The United Nations Office on Drugs and Crime’s (UNODC) Early Warning Advisory noted that by September 2014 25I-NBOMe was the most frequently reported (43%) novel psychoactive substance that year.

NBOMe are sold as blotter paper, powder (loose or within capsules), and liquids with sublingual/buccal and nasal insufflation being the most common routes of administration though inhalation, parenteral, rectal, and vaginal use has been reported. These compounds are marketed as legal or natural LSD and sold under a variety of synonyms, depending on which NBOMe analog the product contains, including: N-Bomb, Solaris, Smiles, Cimbi, C-Boom, INB-MeO, Pandora, Dime, and Holland Film.

While marketed as an alternative to LSD, these compounds are actually derived from the 2C-X series of psychedelics originally developed by Alexander Shulgin in the 1970s. They are synthesized from the 2-CX compounds through the addition of a 2-methoxybenzyl (MeOB) function group onto the nitrogen (N) just off the core structure (hence NBOMe). Each NBOMe variant is differentiated by the specific halogen or other functional group added to the benzene ring (i.e. iodine substitution is 25I-NBOMe).

The pharmacological properties of NBOMe resemble their 2C derivatives which are primarily 5-HT_2A (serotonin-2A) receptor and alpha-adrenergic receptor stimulants. In vitro displacement studies show that 25I-NBOMe is approximately 16-fold more potent at the serotonin receptor than its 2C-I derivative.

Independent reports from human use suggest that the threshold dosage is 50-250μg (micrograms) with a light dose between 200-600μg, a common dose between 500-800μg, and a strong dose between 700-1500μg. At this level of potency, it is impossible to accurately measure a single dose of NBOMe powder without an analytical balance and misjudging the dose could lead to significant toxicity. Furthermore, manipulation of the powder without proper personal protective equipment could result in toxicity due to accidental inhalation or touching of the eyes and/or mouth after handling.

Acute toxicity produces clinical features of both serotonergic and sympathomimetic toxidromes, including: hypertension, tachycardia, dilated pupils, diaphoresis, hyperthermia, agitation, aggressive behavior, delirium, visual and auditory hallucinations, tremulousness, bruxism, myoclonus, muscle rigidity, rhabdomyolysis with subsequent renal failure, seizures, status epilepticus, and coma.

According to medical examiner and postmortem toxicology reports available to the Drug Enforcement Agency (DEA), NBOMe have been implicated in the deaths of at least 17 individuals in the United States just prior to 2014. These reports suggest that 14 of the individuals died of acute toxicity while 3 other fatalities were attributed to unpredictable or violent behavior.

The goal of treatment is to manage agitation and prevent end-organ damage. Agitation or physical aggression may develop and require large doses of benzodiazepines for sedation. Severe cases may require orotracheal intubation and neuromuscular paralysis. External cooling measures may be needed for hyperthermia. If left untreated, hyperthermia will result in disseminated intravascular coagulopathy. At this time, it is unknown if hemodialysis or hemoperfusion would help enhance NBOMe elimination.

References

1. Bersani FS, Corazza O, Albano G, et al. 25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug. Biomed Res Int. 2014; 2014: 734749.
2. Braden MR, Parrish JC, Naylor JC, et al. Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists. Mol Pharmacol. 2006 Dec; 70(6):1956-64.
3. Erowid. 25I-NBOMe (2C-I-NBOMe) Fatalities and deaths. (2015). Retrieved 20 March 2015, from https://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml
4. Hill SL, Doris T, Gurung S, et al. Severe clinical toxicity associated with analytically confirmed recreational use of 25I-NBOMe: case series. Clin Toxicol (Phila). 2013 Jul; 51(6):487-92.
5. Laskowski LK, Elbakoush F, Calvo J, et al. Evolution of the NBOMes: 25C- and 25B- sold as 25I-NBOMe. J Med Toxicol. 2014 Nov 12. [Epub ahead of print]
6. Rose SR, Poklis JL, Poklis A. A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug. Clin Toxicol (Phila). 2013 Mar; 51(3):174-7.
7. Stellpflug SJ, Kealey SE, Hegarty CB, et al. 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. J Med Toxicol. 2014 Mar; 10(1):45-50.
8. Suzuki J, Poklis JL, Poklis A. “My friend said it was good LSD”: a suicide attempt following analytically confirmed 25I-NBOMe ingestion. J Psychoactive Drugs. 2014 Nov-Dec; 46(5):379-82.
9. Tang MH, Ching CK, Tsui MS, et al. Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe. Clin Toxicol (Phila). 2014 Jun; 52(5):561-5.
10. Temporary placement of three synthetic phenethylamines into Schedule I. Fed Reg.  2013 Nov 18; 78(221): 68716-68719 (to be codified at 21 C.F.R pt. 1308). Retrieved from http://www.gpo.gov/fdsys/pkg/FR-2013-11-15/html/2013-27315.htm
11. UNODC-EWA: 25I-NBOMe is the most reported substance in 2014. (Oct 2014). United Nations Office on Drugs and Crime’s (UNODC) Early Warning Advisory (EWA) on New Psychoactive Substances (NPS). Retrieved from https://www.unodc.org/LSS/Announcement/Details/f6acf081-dd51-4d23-9c66-d01eeef5cbf9
12. Walterscheid JP, Phillips GT, Lopez AE, et al. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014 Mar; 35(1):20-5.
13. Wood DM, Sedefov R, Cunningham A, et al. Prevalence of use and acute toxicity associated with the use of NBOMe drugs. Clin Toxicol (Phila). 2015 Feb; 53(2):85-92.

This question prepared by:  Justin Loden, Pharm D  (CSPI)  Certified Specialist in Poison Information

Question of the Week

April 7, 2014

What are electronic cigarettes and why are they so popular?

Electronic cigarettes are also known as e-ciggs and electronic nicotine delivery system. This rechargeable or battery operated device uses a heating element to vaporize liquid containing nicotine or flavors for inhalation. This process of turning the liquid into a vapor is the origin of the term “vaping”.  The e-ciggs are manufactured to resemble regular cigarettes, cigars, pipes and items like pens and USB devices. Several of the e-ciggs are advertised to be nicotine-free. However, the FDA testing revealed e-cigs advertised as nicotine-free, were not. They amount of nicotine varies from 0 to 24 mg/mL of solution. The flavoring agents are dissolved in either glycerol or propylene glycol and are part of the solution composition.

Nicotine is a highly addictive drug. This can lead to worsening addiction and toxicity. Each e-cigg varies greatly with the amount of nicotine being delivered. Users may be using the device in excess and getting more nicotine than they realize, leading to toxic doses. Other harmful chemicals and potential toxic metal particles are being created during the heating process and no data is available on the long term effects. The misconception about the smokeless system is luring many into this fad without realizing the dangers associated with other carcinogens. In 2009, analysis by the FDA detected diethylene glycol and tobacco-specific nitrosamines in two of the leading brands of electronic cigarettes.

Not all states have an age limit on purchase of these products, so they are being utilized by the younger generation. Even if states do have bans on sales to minors, the devices are available online and in kiosks. They are particularly appealing to this age group since they come in candy, coffee and fruit flavors. This is becoming an introduction for many youth to try other tobacco and nicotine containing products. With more e-ciggs being utilized, the number of toddlers getting the products and swallowing the liquid is also on the rise. The amount of nicotine consumed during accidental ingestions is not a known, leading to increases in potential toxicity. The Tennessee Poison Center has had a growing number of e-cigarette related exposures over the last few years.  In 2013 a total of 30 cases were reported. The distribution for e-cigarette and e-cigarette solution is shown below:

Adverse events have been reported to the FDA in association with use of the e-ciggs. Hospitalization was required for pneumonia, congestive heart failure, disorientation, seizures and hypotension in these voluntary reports.

Information of efficacy and safety of electronic cigarettes is not available through the FDA. Currently, no e-ciggs are approved by the FDA for therapeutic use. For this reason they cannot be recommended as smoking cessation aids. Approved treatments for smokers and updated information can be obtained at www.fda.gov.

This question prepared by:  Renee Miller, RN, MSN, Specialist in Poison Information

*Two readers submitted questions about last week’s Question regarding the Ebola outbreak in Guinea. 

One reader asked: How is it transmitted?  Transmission is primarily from direct contact with blood or secretions from infected person.   Also, exposure to contaminated objects, such as needles, may transmit the virus.  In hospitals, it has spread to healthcare workers NOT wearing appropriate protective equipment (masks, gowns, gloves).  

Another reader asked:  What quarantine measures, if any, are being taken for this outbreak?  What government is responsible for facilitating a quarantine in this situation?  The government of Guinea is responsible for the outbreak within their borders.  Neighboring countries governments are dealing with it locally (Sierra Leone and Liberia).  The appropriate Ministries of Health are the specific agencies working on this.  They are being assisted by the World Health Organization, Medecins sans Frontieres (MOH, Doctors without Borders) are also helping with treatment and isolation centers.  In Liberia the International Red Cross, Pentecostal Mission Unlimited-Liberia and Samaritan’s Purse are aiding the Ministry of Health.  CDC has sent a 5 person team to Guinea to assist the Guinea MOH and WHO.

So, what is the current situation?  According to the WHO and the Ministry of Health of Guinea the current total is 127 probable and suspect cases, including 83 deaths.  The case fatality ratio is up to 65% as of 1 April 2014.  Of the suspect cases, 35 are laboratory confirmed to have Ebola hemorrhagic fever, and includes 14 health care workers.  Also, cases have now been confirmed in the capital of Guinea, Conakry (11 cases).  Liberia has now reported 8 suspect cases which includes 5 deaths and 2 laboratory confirmed cases of EHF from people that have recently travelled to Guinea.  Additional suspect cases are under investigation in Liberia and Sierra Leone.

References:

www.cdc.gov/vhf/ebola/outbreaks/guinea

http://www.who.int/csr/don/2014_04_ebola/en/

The Ebola questions answered by:  John G. Benitez, MD, MPH  Medical Toxicologist

Question of the Week

April 4, 2011

What is in Molly’s Plant Food?  (one of the latest recreational drug rages to affect Tennessee’s teens and young adults)

Molly’s Plant Food is a synthetic hallucinogenic amphetamine marketed as a “plant food” that contains ingredients that produce highs similar to Ecstasy. Molly’s Plant Food is usually purchased at a convenience store and is packaged in a capsule form with a cost of $8-$12 per capsule. The product label warns “not for human consumption”; however it is packaged in a psychedelic colored wrapper and several Internet web sites and chat rooms refer to the product as “legal ecstasy”. The active ingredient is mephedrone, which is not a scheduled (DEA) drug, therefore making it legal.

Over the past six months, The Tennessee Poison Control Center has received an increasing number of calls from emergency departments regarding symptomatic patients who have ingested or snorted Molly’s Plant Food. Clinical effects include euphoria, anxiety, paranoia, agitation, tachycardia, hypertension, delusions, diaphoresis, and weight loss. The treatment is supportive with intravenous fluids and benzodiazepines. Signs and symptoms have lasted an average of 24-48 hours.

This past week brought good news. Under an emergency court order sought by the Tennessee Agriculture Commissioner and the Attorney General, sheriff narcotic detectives have been removing the products from convenience stores in Rutherford County. Since Molly’s Plant Food is titled a “plant food”, it must be registered with the state as a fertilizer (the purported use of Molly’s Plant Food) and clearly list its ingredients. Molly’s Plant Food has neither been registered nor are the ingredients listed on the package.

This question prepared by Marilyn Weber, CSPI, MSN, RN Tennessee Poison Control Center

Question of the Week

January 31, 2011

Are bath salts for more than bathing?

Apparently so.  Recently there has been much media attention about packets labeled as “ bath salts” which are sold in convenience stores.  Although the packets include the warning “not for human consumption”, they are actually designed for insufflation (snorting).  The packets reportedly contain drugs such as ephedrone (methcathinone), mephedrone (4-methylmethcathinone), or MDPV (3,4-methylenedioxyprovalerone).  Ephedrone (also known as “Bathtub speed” “Gaggers” “Cadillac Express”) and mephedrone are synthetic cathinone derivatives which are chemically similar to a psychoactive stimulant in the khat plant. They probably cause the release of dopamine, norepimephrine, and serotonin. MDPV, also known as “Magic” or Super Coke”, is a designer drug sold as a stimulant for recreational use.  All three of these drugs are powerful stimulants.  The bath powders are sold as “Ivory Wave”  “Charge Plus” “White Lightning” “Scarface” etc.  You get the picture.

Clinically, one would expect to see stimulant effects from these drugs.  What have been reported is strong psychoactive effects such as hallucinations and paranoia. As a result, there have been reports of violent behavior and suicides. 

There is nothing unique about treatment of patients with this exposure.  Assessment and treatment of complications from stimulants (hyperthermia, rhabdomyolysis, hepatic and renal failure, etc.) is warranted although supportive care will be the mainstay.  None of these drugs will be found on a routine urine drug screen.  

This question prepared by: Donna Seger, MD  Medical Toxicologist

Question of the Week

March 1, 2010

What is “parachuting” and what does it have to do with drug abuse?

“Parachuting” is a term that is used to describe the technique of crushing up a pill, placing the crumbs into a tissue, wrapping this into a “parachute”, and then swallowing the tissue wrapped crushed drug. The intent is to increase the immediate absorption of the drug by increasing its surface area. The purpose of “parachuting” is a faster onset, higher intensity effect of the xenobiotic.  For extended release tablets, crushing the outer coating usually destroys delayed release mechanism. The use of the tissue or toilet paper makes the crumbles of the pill easier to swallow and reduces the unpleasant taste of most crushed pills. Tissue is used since it tends to disintegrate easily with application of moisture.

If the drug abuser uses a different medium to wrap the crumbs other than a rapidly disintegrating material, absorption may be delayed or not occur at all, such as in the case of a sealed plastic sandwich baggy.  This technique is not to be confused with the “body stuffer” who suddenly ingests packaged or unpackaged illicit drugs in an effort to quickly “dispose” of the evidence. In either case, rapid release of drug and subsequent clinical effects may occur.

Question prepared by:  Saralyn Williams, MD  Medical Toxicologist

Why is agranulocytosis occurring in cocaine users?

The New Mexico Department of Health (NMDOH) has issued a health alert regarding a cluster of patients who presented with agranulocytosis over the past 15 months and had cocaine use in common. Most of the cases are in New Mexico, but there also have been cases in Arizona and in Colorado. NMDOH believes that levamisole, an antimetabolic drug used in veterinary practice as a de-worming agent, may have contaminated the cocaine. Levamisole has been detected in cocaine samples in New Mexico and in a post-mortem blood sample of one of New Mexico's cocaine-using agranulocytosis cases. Death may occur secondary to infection in immunocompromised patients. Previous cases have been noted in Canada and California. There is no evidence that the type of cocaine (e.g. powder or crack) or route of use affects the risk for agranulocytosis.

Consider agranulocytosis in cocaine users with recent signs and/or symptoms of infection.
a) Perform a CBC w/ manual differential in potential cases. Peripheral blood smears have shown a marked decrease or absence of neutrophils.
b) Obtain microbiologic cultures of blood, wounds and body fluids in febrile patients.

If you see a patient with cocaine use and agranulocytosis, please call the TN Poison Center and ask to speak to the Toxicologist-on-call.

Question prepared by: Donna L. Seger, M.D. Medical Toxicologist

What is the Initial Evaluation of Children Living in Homes with Methamphetamine Labs?

Recently, there has been media attention regarding the medical community’s evaluation of children living in homes where there is a methamphetamine lab. The medical community is being asked to assess the child that has been found in such a house. Multiple protocols have been proposed, based on little research data.  Protocols range from “do nothing” to “do everything,” including CT scans, drug analysis, etc. 

A national committee from within the American College of Medical Toxicology (ACMT) is currently addressing this issue (supported by the Agency for Toxic Substance and Disease Registry (ATSDR)).  Hopefully, within a year, there will be some guidelines about many aspects of methamphetamine labs (including the initial evaluation of children).  Until these guidelines are announced, the Medical Toxicologists at Tennessee Poison Center make the following recommendations.

The most common poisons found in methamphetamine production sites include solvents, ephedrine, acids, iodine, lye, phosphorus, and salt.

The dangers from living in a home that houses a methamphetamine lab include:

1)  injury or death from fire or explosions from flammable materials used in the lab

2)  poisoning from accidental ingestion or absorption of accessible chemicals

3)  upper respiratory symptoms, headaches, rashes from exposure to chemicals in the environment (inhalation , skin contact)

4)  chemical burns

5)  long term health effects, such as asthma, neurologic problems

6)  nutrition

7)  emotional or physical neglect

Questions regarding a child found in the home producing methamphetamine are the need for decontamination and the need for an immediate evaluation by a health care provider.

Decontamination

If there is residue on the clothes of an asymptomatic child, clothing can be changed prior to transfer.  Alternatively, the children can be given something disposable to sit on (newspaper, diaper) and then change clothes later on if need be.  The children should take a shower at some time, but do not need to be decontaminated at the scene.  Take the least traumatic approach.  Do not take toys or any materials from the house.

Initial Evaluation

Need for immediate evaluation by a health care provider can be determined by assessing if the child is asymptomatic or symptomatic. 

• Asymptomatic

Asymptomatic children do not need to be immediately evaluated by a physician. If the paramedic or policeman find a child that is completely asymptomatic, there is no need to take that child to the emergency department (ED). If there is a requirement for the child to be evaluated by a physician before the child can be placed in the appropriate social setting, then ED evaluation requires only a history and physical exam.

Children can subsequently be followed-up at their pediatrician’s office where issues such as neglect can be addressed. 

• Symptomatic

For the symptomatic child, the workup should include a physical exam and history.  The laboratory testing should be based on PE findings or concerning symptoms.  A medical toxicologist is always available by calling Tennessee Poison Center. Either Dr. Williams or I will discuss specific aspects of the case.

Although there are concerns about the long-term effects of these exposures, there is not an initial evaluation or intervention that can identify or change the long-term outcome.

We will be developing more extensive recommendations and disseminating them to all Tennessee emergency departments and pediatricians in the near future.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at Donna.Seger@Vanderbilt.edu.

Donna Seger, MD

Medical Director

Tennessee Poison Center

Does education about inhalants increase the abuse of inhalants in preteens and teenagers?

Inhalant abuse is rampant in Tennessee.  In fact, our state ranks number 7^th in the country for incidence of inhalant abuse. 

One of our pediatricians has asked an excellent question.  Exactly how much information should we give parents and teens about inhalants?  Will increasing their knowledge about inhalants increase the chance that they will use it?

First - our kids already know about inhalants.

One in five students in America has used an inhalant to get high by the time he or she reaches the eighth grade. Parents don't know that inhalants - cheap, legal and accessible products - are as popular among middle school students as marijuana. Even fewer know the deadly effects of “sniffing” “bagging” and “huffing”. It's like playing Russian Roulette. The user can die the 1st, 10th or 100th time a product is misused as an inhalant.

So although the kids know, we need to educate the parents. Tennessee Poison Center has a brochure, Inhalants Are Poisons, that is available in English and Spanish. The brochure explains inhalant abuse and its dangers. You can request copies of this brochure for your patients by calling our administrative office at 936-0760. 

Here are some recommendations from Poison Educators regarding talking to middle school students about inhalants:

Do:

• Equate inhalants with poisons, pollutants, and fire hazards
• Point out that everyday products can be poisons, pollutants, and fire hazards when used incorrectly.
• Stress using products as they were intended to be used
• Substitute “toxic effects” for “get high”
• Say poisons, chemicals, toxins, fumes instead of inhalants or drugs
• Emphasize reading product labels and following directions. Give examples of what “well ventilated” and “avoid concentrating fumes” mean.

Do not:

• Group inhalants in with other drugs
• Over exaggerate negative effects on the body
• Talk about the “high” or “head rush”
• Identify specific products used in abusing inhalants
• Demonstrate how products are misused

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at Donna.Seger@vumc.org. 

Donna Seger, MD

Medical Director

Tennessee Poison Center