Lạm dụng các loại ma túy mới: ý nghĩa lâm sàng

 Drugs like Molly, MDMA, 2C-E, bath salts, tend.. to be a small segment of drug use.[r]

Emerging Drugs of Abuse: Clinical Implications

Scott Phillips, MD, FACP, FACMT, FAACT Associate Medical Director

“Synthetic” Drugs

 Drugs like Molly, MDMA, 2C-E, bath salts, tend

to be a small segment of drug use

 Present a problem because they rapidly change

History

 1990s: surge in use of

3,4-methylenedioxy-N-methylamphetamine (MDMA), rave drugs

 Many new derivatives available now

 Most contain little MDMA

 Amphetamine, DXM, BZP, etc

 Next generation includes:

 Tryptamines

 Phenylethylamines

Tryptamines

 Re-emerged on drug scene

 Include DMT, 5-MeO-DIPT, 5-MeO-DMT,

and more

 Yakee plant, Foxy methoxy, alpha-O, O-DMS,

alpha and bufo toad secretions

 Similar to psilocybin, psilocin, and bufotenine

 Derivatives of tryptamine contain stimulant

Tryptamine Pharmacology

 Mechanism of action not fully elucidated  Similar to classical hallucinogens like LSD

 Direct agonists at 5-HT2A and 5-HT1C

 Presentation includes

 Empathy

 Euphoria

 Visual/auditory hallucinations  Tachycardia/HTN

 Confusion  Seizures

Dimethyltryptamine (DMT)  DMT discovered in

1960s

 “Businessman’s

lunch”

 DMT used in South

America for spiritual and medicinal

purposes

 Available in various

Management of Tryptamine Toxicity

 Treatment

 Supportive care  No antidotes

 Nice, quiet dark room

Phenylethylamines

 Newer designer analogues designated “2C”

series

 DOM: STP (Serenity, Tranquility, & Peace)  Mescaline: Mesc, Buttons, Cactus

 2C-B: Nexus, Bromo, Bees, Venus  2C-T-2: Triptasy or Beautiful

 2C-E: Europa, Eternity

 2C-T-7: Blue Mystic and 7th Heaven

Phenylethylamines

 Pharmacology similar to bath salts

 Affect dopamine, norepinephrine and serotonin

 Increase release of catecholamines and inhibit the

reuptake of them

 Ring substitutions increase affinity for 5-HT2

receptors

 Agonist properties at other 5-HT substypes

and α1-adrenergic receptor

Phenylethylamines  Hallucinations

 Visual and auditory

 Euphoria  Entactogen  Tachycardia  Paranoia  Delirium  Bruxism

 Violent behavior

 Refractory seizures

and serotonin toxicity with 2C-I reported

 Recently in Seattle

 Death in 15 yo by

25i-NBOMe

 Fatal cardiac arrest

after 2C-E

 No literature on

Molly

 Highly purified form of MDMA

 Methylene-dioxy-methamphetamine

 Oftentimes contains very little MDMA

 Other drugs sold as Molly

 MDMA is neurotoxic even with a single dose

 Destroys 5-HT receptors and serotonergic neurons  Long terms effects result in neuroendocrine

impairments to deficits in verbal memory and reasoning

 Chronic psychosis responds poorly to traditional

therapy

Management  In the ED

 Management largely supportive

 Benzodiazepines as indicated for sympathomimetic

symptoms

 Hyperthermia is what kills these patients  Body temps of 111 degrees F

 Rapid cooling with ice and chilled saline fluids

“NMUO”

Opiate Prescribing

 Steady increase in opioid prescribing from 2006,

 Total # of Rx’s peaked in 2012 at >255 million and a rate of 81.3 Rx per 100  The overall national opioid prescribing rate declined from 2012 to

2016

 In 2016, the Rx rate had fallen to the lowest in 10 years at 66.5 Rx per 100

 over 214 million total opioid prescriptions)

 However, in 2016, prescribing rates continue to remain very high in

areas across the country

 In ¼ of U.S counties, opioid Rx’s were dispensed for every

person

 Opioid prescribing rate in 2016 was 66.5 prescriptions per 100

Fentanyl

 50-100 times > potent than Morphine

 50 times > than heroin

 kg can make million tablets

 20-80 USD per tablet

Methamphetamine History

 Developed in late 1800s and used during

WWII to keep troops awake

 Given to pilots to enhance “performance”

 Used previously as diet aid, antidepressant,

stimulant, and drug of abuse

 Street names

 Speed, Krystal meth, Tina, Ice, Crank,

Management

Where did it come from?

 1960s: research into THC-like compounds

 Analgesic and anti-inflammatory minus

psychotropic effects

 Recognized as drugs of abuse in early 2000’s

in Europe

 Dr JW Huffman researched THC analogues

for use in cancer and AIDS patients  Developer of JWH compounds

What are they?

 Synthetic cannabinoids which work on the

CB1 and CB2 receptor like THC

 Marketed as herbal incense, herbal smoking

blends, potpourri, etc

 Spice, K2, Mr Nice Guy, Legal Funk, Tai Fun  Misleading packaging

 Not for human consumption

 Commonly smoked

 New chemicals like PINACA and

Pharmacology

 Effects likely from mixture of herbs and actual

synthetic compounds

 Baybean, Beach bean, Dwarf skullcap, red clover,

vanilla, honey, wild dagga and more

 Affects CB1 and CB2 receptors found in

CNS/PNS

 Responsible for elevating mood, anxiety, cognition  Responsible for reducing inflammation induced pain

Clinical Manifestation

 Most information from case reports and case

series

 Psychiatric effects predominate

 Anxiety, paranoia, agitation, delusions, and

psychosis

 Physical manifestations

 Tachycardia, HTN, diaphoresis, seizures, muscle

Management

 Agitated Delirium

 Like bath salts, unpredictable

 ABCs

 GI decontamination

 No antidote

 Supportive care

What are bath salts?

 Synthetic cathinone derivatives

 Synthesized as early as 1928 and studied for

medical use

 Methcathinone (1928)  Mephedrone (1929)

 Used as antidepressant in 1930s in Soviet

Union

 Bupropion only cathinone with medical

Common Synthetic Cathinones and Names

α-PVP

 α-Pyrrolidinopentiophenone (also known as

α-pyrrolidinovalerophenone, α-PVP, O-2387, β-keto-prolintane, prolintanone, or

desmethylpyrovalerone) “Flakka”

 Substituted cathinone & pyrrolidine

 Developed in the 1960s

 Heightened tactile enhancement

 Norepinephrine-dopamine reuptake inhibitor

Pharmacology

 β-ketonated amphetamines

 Ketone on β carbon leads to decreased CNS

penetration  increased doses  increased effects

Clinical Manifestations  Agitation (53.3%)

 Tachycardia (40%)  Hypertension (20%)  Seizures (20%)

 Palpitations (13.3%)

 Hallucinations/delusions  Paranoia

 Renal failure

Management  Protect yourself!

 Difficult to manage patients and unpredictable

behavior

 ABCs

 No antidote

 GI decontamination

 Benzodiazepines, barbiturates for agitation,

hallucinations and seizures

 Caution against using haloperidol

Loperamide & Diphenoxylate Abuse

 Inexpensive OTC anti-diarrheal with peripheral mu opioid

receptor activity

 200 - 400 tablets of Loperamide mg daily  Produces cardiac conduction abnormality

 QTc > 600 msec

 Normal up to 460

 High risk for TdP

 Mechanism of toxicity unknown

 Watch for patients purchasing MASSIVE quantities of

Other Common Drugs of Abuse  Diphenhydramine

 Anticholinergic toxicity  Lilliputian

hallucinations

 Physostigmine?

 DXM

 “Robotripping” or

“Triple C’s”

 Hallucinations and

euphoria

 Serotonin syndrome

 Nutmeg

 Contains myristicin  Causes LSD-like

hallucinations

 Ingest grams

 Morning Glory Seeds

 Contains LSD-like

alkaloid

 Hallucinations  N/V