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6/24/2013
The New Synthetic Drugs
Sullivan Smith, MD, FACEP
Cookeville Regional Medical Center
Cookeville Police Department
Bath Salts, Plant Food
At First, It Was Molly’s
• Bath Salts…Not
• Plant Food…Not
DOPE…Absolutely
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What is this?
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Various drugs
“Legal Ecstasy”
$20 - $40-$80 @ stores, even now
Internet
Stock up!
Reportedly #1 drug at Bonnaroo
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A Few Names
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Molly’s Plant Food
Purple Monkey PF
Rave On Bath Salts
Magic
Super Coke
Sprinklz
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Gaggers
Ivory Wave BS
Charge Plus
White Lightning
Scarface
Purple Dragon
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Science
Science
• Weak, Grade C2
• New substances, little research
• Mostly consensus or very small series
• Toxicology of bath salts, a review of
synthetic cathinones.
J Med Toxicol 2012; 8:33
Metabolism of designer drugs of abuse: an updated review.
, Maurer HH.
Department of Experimental and Clinical Toxicology, Institute of
Experimental and Clinical Pharmacology and Toxicology, Saarland,
University, Homburg (Saar), Germany.
Meyer MR
Abstract
This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented
review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (2C-B), 4-iodo-2,5-dimethoxy-beta-phenethylamine
(2C-I), 2,5-dimethoxy-4-methyl-beta-phenethylamine (2C-D), 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E), 4-ethylthio-2,5-dimethoxy-beta-phenethylamine (2C-T-2), and 2,5-dimethoxy4-propylthio-beta-phenethylamine (2C-T-7), beta-keto designer drugs such as 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (butylone, bk-MBDB), 2-ethylamino-1-(3,4methylenedioxyphenyl)propan-1-one (ethylone, bk-MDEA), 2-methylamino-1-(3,4-methylene notdioxy notphenyl)propan-1-one (methylone, bk-MDMA), and 2-methylamino-1-p-tolylpropane-1one (mephedrone, 4-methyl-methcathinone), pyrrolidino notphenones such as 4-methyl-pyrrolidinobutyrophenone (MPBP) and alpha-pyrrolidinovalerophenone (PVP), phencyclidine-derived
drugs such as N (1 phenylcyclohexyl) propanamine (PCPr), N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA), N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA), and N-(1phenylcyclohexyl)-2-methoxyethanamine (PCMEA), tryptamines such as 5-methoxy-N,N-diisopropyl nottryptamine (5-MeO-DIPT), and finally alpha-methylfentanyl (alpha-MF) and 3methylfentanyl (3-MF). Papers have been considered and reviewed on the identification of in vivo or in vitro human or animal metabolites and the cytochrome P450 or monoamineoxidase
isoenzyme-dependent metabolism.
PMID: 20540700 [PubMed - indexed for MEDLINE]
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Legal
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US Controlled Substance Act Section
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Clearly analogues of khat (Catha edulis)
“Not intended for human consumption”
Near miss
Call it whatever you want
Problem?
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• Absolutely
– So many stories
– At times more than a case per shift in ER
– That we know about
• Not revealed on drug screen
• Several others fit pattern
• High Schools in Putnam County
• Colleges in Tennessee
Toxicology
• Release neurotransmitters:
serotonin, dopamine, norepinephrine
• Inhibit reuptake
• Specific effects depend upon the drug
• Lipophilic: easily cross blood brain barrier
• Hepatic metabolism, renal elimination
• Tolerance and addiction shown
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Toxicology
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Injected, smoked, inhaled, oral
Peaks in about 1-2 hrs orally
Much faster injected etc…
Large volume distribution 3-6L/kg
T1/2 varies 3-24 hrs
May go well beyond this…
Effects
• Hyperdynamic
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• Movement disorders
HTN/Tachycardic
Hyperthermic
Nystagmus/Mydriasis
Electrolyte disorders
Seizures
– Serotonin effects
– Manganese
• Terrified
• Violence
• Suicidal
Death
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Arrhythmia
Hyperthermia
Intracerebral Hemorrhage
But how do you know for sure?
• These are clinical diagnoses
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Drug Screens
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Of course
Often polysubstance ingestions, helpful
A couple are testable, but are send outs
GC/LC mass spec needed
Dead or alive by the time you know
Clinical diagnosis
Testing
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Glucose
Acetaminophen
Salicylate
EKG (ischemia/QRS)
Pregnancy
Electrolytes
CK
Urine myoglobin
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UA
Creatnine
Hepatic functions
Coags
Blood alcohol
• ? CT head?
• ? Troponin?
Differential DX
• Hallucinogen (LSD, psilocybin)
– No adrenergic sx
• Anticholinergic
– No diaphoresis, mydriasis, or flushed skin
• Thyroxtoxicosis
– Eyelid retraction and lag
• Heat stroke, paranoid schizophrenia,
pheochromocytoma
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Treatment
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No antidote
Supportive care
SEDATION SEDATION SEDATION
Fluids
Cooling
Treatment
• Sedation
• Benzodiazepines
– We like midazolam (Versed)
• How much?
– How much do you need?
– How much do you have?
– How much can you get?
Treatment
• Benzodiazepines
• Fluids in sepsis doses (20 ml/kg NS)
• Small doses of haldol or ziprasidone
– NOT FIRST LINE
– Seizure threshold, prolong QT, heat retention
• Ketamine (5-10 mg/kg IM, 5mg/kg IV)
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Treatment
• PROTECT YOURSELF!
• May need intubation, that’s OK
• PROTECT YOURSELF!
• See above.
Excited Delirium
• Is it real?
• Dr Bell, 1849, Exhaustive Mania
– 40 cases, sound similar
– ¾ died
• Related to neuroleptic malignant syndrome?
• Variants of the same problem?
• Not a lot of data yet
Excited Delirium
• Defect of Dopamine
Transporters/Regulation?
• These are Dopamine drugs
• Perfect set up for Excited Delirium
• Elevated heat shock porteins, c-fos protein
• Act quickly
• Potential for DEATH very real
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Excited Delirium Prehospital
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Coordinate w/ LEO and EMS
Do this as early as possible
Contain and buy some time if possible
Control subject followed by immediate
sedation and fluid resuscitation
• Give your hospital a heads up
• Train for this
Synthetic Cannibinoids
Synthetic Cannibinoids
• Group of chemicals that bind to same
receptors as THC in brain
• HU-210, CP-47, CP-497, JWH-018,
JWH-187
• More than 100 of these chemical have been
identified
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9 delta tetra hydrocannibinol
JWH-018
JWH-018
• First synthesized by John Huffman
• Clemson University
• “The people who use this stuff are idiots.”
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More troubles
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Not just these chemicals
Non pharmaceutical reagents
Special add ins
No way to know what you are getting
7H
Plan of Attack
• Education
– Medical
– Law Enforcement
– Retail
• Legislation
– Became Effective May 2011
– Analogues included
– Pseudo
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TN Bills/Laws
• SB 329 Stewart, HB 304 Curtiss
– Controls mephedrone as Sch I
– Fiscal Note
– Died
• SB 396 Burks, HB 457 Williams
– Class A Misdemeanor to sell/distribute
– PASSED!
– Includes analogues
Federal Legislation
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Only Mephedrone and MDPV originally
Expanded to include analogues
Become Schedule I
House Judiciary Committee Subcommittee on
Crime & Terrorism
• Slow progress (other issues in DC)
• Sen Schumer (D-NY) Rep Stevens (R-FL)
• So what happened?????????
Here’s What Happened
• Resistance in face of Senate rules a problem
• HR 1254 “Synthetic Drug Control Act of
2011”
• Included into SB 3187/PL 112-144 “Food
and Drug Administration Safety and
Innovation Act.”
• And???
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SB 3187/PL 112-144
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Essentially hits all synthetic cannibis
Hits only 2 bath salts.
Gives DEA emergency scheduling authority
Signed in July, 2012.
To date, only 2 chemical moved into
Schedule I by the DEA. (220+ known)
• Over 200 have been identified in US.
Then What?
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New Bill introduced
Jo Ann Peterson, (R-MO)
HR 6312 schedules balance of the bath salts
Little traction, Washington distracted
Died (Referred to Committee)
Stay tuned….
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“There is just one more thing…”
FDA warns about serious blood disorder resulting from
misuse of Opana ER
UPDATE [11-01-2012] Updated information provided to FDA indicates that no deaths have been confirmed in persons who developed TTP after abusing Opana ER by
intravenous injection; however, other serious adverse events have occurred, as described below.
[10-11-2012] The U.S. Food and Drug Administration (FDA) recently became aware of cases of a serious blood disorder that occurred in individuals abusing the
prescription pain medicine Opana ER (oxymorphone hydrochloride extended-release tablets) by injecting the drug into their bloodstream. This serious blood disorder,
called thrombotic thrombocytopenic purpura (TTP), resulted in kidney failure requiring dialysis in some cases, and at least one death.
In TTP, blood clots form in small blood vessels throughout the body. The clots can limit or block blood flow to the body’s organs, such as the kidneys, brain, and heart.
Certain blood cells called platelets help the blood to clot. In TTP, as platelets clump together in the blood clots, fewer platelets are available in the blood in other parts of
the body to help with clotting there. This can lead to bleeding under the skin and purple-colored spots called purpura, or to bleeding inside the body. TTP can cause death
or lead to other complications with permanent damage, such as kidney failure, brain damage, or stroke.
TTP appears to occur with Opana ER only when it is abused and injected intravenously. Opana ER is meant to be taken orally, and should only be taken when prescribed
and as directed. Taking it any other way may result in serious adverse events, including death.
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“There is just one more thing…”
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Oxymorphone causing renal failure
Opana
1.25mg = 10 mg morphine orally
Now used IV & probably due to tablet
constituents
• TTP like syndrome
• 14th case in country
Questions?
[email protected]
Excited Delirium
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Metabolism of designer drugs of abuse: an updated review.
, Maurer HH.
Department of Experimental and Clinical Toxicology, Institute of
Experimental and Clinical Pharmacology and Toxicology, Saarland,
University, Homburg (Saar), Germany.
Meyer MR
Abstract
This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented
review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (2C-B), 4-iodo-2,5-dimethoxy-beta-phenethylamine
(2C-I), 2,5-dimethoxy-4-methyl-beta-phenethylamine (2C-D), 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E), 4-ethylthio-2,5-dimethoxy-beta-phenethylamine (2C-T-2), and 2,5-dimethoxy4-propylthio-beta-phenethylamine (2C-T-7), beta-keto designer drugs such as 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one (butylone, bk-MBDB), 2-ethylamino-1-(3,4methylenedioxyphenyl)propan-1-one (ethylone, bk-MDEA), 2-methylamino-1-(3,4-methylene notdioxy notphenyl)propan-1-one (methylone, bk-MDMA), and 2-methylamino-1-p-tolylpropane-1one (mephedrone, 4-methyl-methcathinone), pyrrolidino notphenones such as 4-methyl-pyrrolidinobutyrophenone (MPBP) and alpha-pyrrolidinovalerophenone (PVP), phencyclidine-derived
drugs such as N (1 phenylcyclohexyl) propanamine (PCPr), N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA), N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA), and N-(1phenylcyclohexyl)-2-methoxyethanamine (PCMEA), tryptamines such as 5-methoxy-N,N-diisopropyl nottryptamine (5-MeO-DIPT), and finally alpha-methylfentanyl (alpha-MF) and 3methylfentanyl (3-MF). Papers have been considered and reviewed on the identification of in vivo or in vitro human or animal metabolites and the cytochrome P450 or monoamineoxidase
isoenzyme-dependent metabolism.
PMID: 20540700 [PubMed - indexed for MEDLINE]
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s
The presented
review contains data concerning the so-called 2C
&
compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-b
phenethylamine
(2C-B), 4-iodo-2,5-dimethoxy-beta-phenethylamine
S
(2C-I),t 2,5-dimethoxy-4-methyl-beta-phenethylamine (2C-D), 4-ethy
2,5-dimethoxy-beta-phenethylamine
(2C-E), 4-ethylthio-2,5-dimetho
r
beta-phenethylamine
(2C-T-2), and 2,5-dimethoxy-4-propylthio-betau
phenethylamine
(2C-T-7), beta-keto designer drugs such as 2c
methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one
(butylone, b
t
MBDB),
u 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one
(ethylone,
r bk-MDEA), 2-methylamino-1-(3,4-methylene notdioxy
notphenyl)propan-1-one
(methylone, bk-MDMA), and 2-methylamin
e
p-tolylpropane-1-one
(mephedrone, 4-methyl-methcathinone),
s
pyrrolidino notphenones such as 4-methyl-pyrrolidinobutyrophenone
(MPBP)
R and alpha-pyrrolidinovalerophenone (PVP), phencyclidinederivede drugs such as N (1 phenylcyclohexyl) propanamine (PCPr), N
(1-phenylcyclohexyl)-2-ethoxyethanamine
(PCEEA), N-(1s
phenylcyclohexyl)-3-methoxypropanamine
(PCMPA), and N-(1o
h l l h l) 2
th
th
i (PCMEA) t t i
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Medical Effects
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Fast Heart
High Blood Pressure
Dilated Pupils, Nystagmus
High Temperature
Hallucinations
Suicidal Ideation – multiple suicides from
Missouri to Lousiana
• Violence
• Seizures
9-delta tetra hydrocannibinol
New Designer Drugs
AKA Plant Food / Bath Salts
Sullivan Smith MD FACEP
Cookeville Regional Medical Center
Cookeville Police Department
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