Project: Ghana Emergency Medicine Collaborative
Document Title: Drugs of Abuse
Author(s): Tim Albertson, M.D., Ph.D. (Univ...
Attribution Key
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{ Content the ...
Update on Drugs of
Abuse (“some club-drug stuff”)
Tim Albertson, M.D.,Ph.D.
Professor of Medicine, Pharmacology
and Toxico...
Overview of Topics
! Gamma hydroxybutyrate (GHB)
–  GHB
–  GHB Analogs
–  GHB / Analog Withdrawal
! Ecstasy : MDMA (Methyl...
Overview of Topics
! Methamphetamine
! Dextromethorphan (DM)
! Ketamine
! Flunitrazepam
! Mescaline
! Inhalants
! Antichol...
United States Department of Justice, Wikimedia Commons

GHB
(Gammahydroxybutyrate)
What is GHB?
! Gamma hydroxybutyrate
! Naturally occurring in brain tissue
–  neurotransmitter-like substance
–  dopamine ...
GHB
! Investigated as an anesthetic agent :

!
!
!
!

caused myoclonus and delirium ; current
IND for sleep apnea
Crystall...
Structure Activity
Relationship
COOH

COOH

CH2

CH2

CH2

CH2

CH2

CH2

OH

GHB
gamma
hydroxybutyrate

NH2

GABA
gamma
a...
History of GHB
! 1960’s
! 1987
! 1990-1
! 1992-5
! 1996
! 1997
! 2000
! 2002

France - Synthesized as an Anesthetic
Orphan...
Slang Names :
Gamma Hydroxybutyrate
! Cherry meth

! Liquid E

! Easy lay

! Liquid X

! G, G caps

! Liquid ecstasy

! Ga...
What are GHB Analogs?
! Organic solvents
–  √-Butyrolactone, 2(3) Dihydrofuranone,
–  1,4-Butanediol, Tetramethylene Glyco...
Conversion :
Gamma Butyrolactone (GBL)
O	


GBL

NaOH + H2O
in vitro
=O	

 Lactonase
In vivo

C OOH
CH2
CH2
CH2 OH

GHB
Gamma Butyrolactone
(GBL)

United States Department of Justice, Wikimedia Commons
Slang Names :
Gamma Butyrolactone or Dihydro
Furanone
! Blue Nitro

! Invigorate

! Firewater

! Jolt

! Furanone Extreme ...
Source Undetermined

Renewtrient and Blue Nitro,
GHB precursors, have been
removed from the market.
Slang Terms :
1,4 Butanediol or Tetramethylene
glycol
! Biocopia PM

! Thunder Nectar

! Borametz

! Pro G

! BVM

! Promu...
Incidence : GHB and
Precursors
400

356

350

C
A
S
E
S

300
250

232
199

200
150
89

100
50
0

18

10

34
9

19

105

37...
Pathology
! Structurally similar to GABA
! Stimulates GABAB receptors
! Influences dopamine release from

substantia nigra...
GHB / Analogs :
Clinical Presentation
! Vomiting, Coma, Bradycardia
! Myoclonic jerking
! Loss of protective airway reflex...
Effects
! “DESIRED”

! UNDESIRED

Euphoria
Mood elevation
Hallucinations
GH-Muscle
growth?
! Amnesia

! Decreased HR,

!
!...
Emergency Department (ED) Course of
Gamma Hydroxybutyric Acid (GHB)
Intoxication Study Acad Emerg Med 2002 Jul;9(7):730-9 ...
Case Study …..
! 26 y/o F with chronic insomnia doubled

her dose of Blue Nitro (GBL) : 3 oz.
– Vomiting within 15 minutes...
Case Study continued ….
! Unresponsive to pain, GCS 3.
! CT scan normal, glucose 125
! No response to naloxone or flumazen...
GHB / Analogs : Kinetics
! Onset

15 minutes

–  Immediate conversion of analogs to GHB

! Coma
!
!
!
!

within 30 minutes...
Emergence Delirium
! Myoclonic jerking motions
! Confusion, agitation, combativeness
–  Transient symptoms (< 30 minutes)
...
GHB / Analogs : Diagnosis
! History of use and circumstances
! Clinical Presentation
! Short Duration
! Role of Laboratory...
GHB / Analogs : Treatment
! Supportive Care
–  Approximately 35 % patients require
airway protection
! Gastrointestinal De...
GHB Dependence : Case Study
! 29 year old male started taking GHB for

the “anabolic effects” 2 yrs ago
! Gradually increa...
Case Study continued ….
– Patient was highly agitated
– Visual and auditory hallucinations
– Delusional, paranoid
– Tremul...
Case Study continued ...
! Patient received :
–  Ativan : 90 mg in the first 24 hours
–  Phenobarbital, Haloperidol
! 10 d...
GHB Withdrawal
! Similar to ETOH and sedative-hypnotic

withdrawal.
! Symptoms start within a few hours of

discontinuatio...
GHB Withdrawal : Clinical
Presentation
! Onset : 1 to 6 hours
! Progression of sxs over 1 to 3 days
! Symptoms
–  Agitatio...
GHB Withdrawal :
Management
!   AGGRESSIVE TREATMENT EARLY
! Benzodiazepines
! High doses may be required
! Barbiturates
!...
Stimulants of Abuse
! Methamphetamine
! Methylene dioxymethamphetamine :

MDMA (Ecstasy)
! Cocaine
! Ketamine / PCP (phenc...
Rave Party : Case Study ...
! 18 year old F was at a Rave party with a

friend. She was drinking ethanol and
using the fol...
Case Study continued ….
!
!
!
!

In ED, comatose but not cyanotic.
Intubated for airway protection.
No response to flumaze...
Ketamine : Clinical
Presentation
! Dissociative anesthetic
! Clinical Presentation
–  Separation of perception and sensati...
Ketamine Treatment
! Supportive
! Sedation
Phencyclidine Effects
! Tremors, agitation, hallucinations :

visual and auditory.
! Tachycardia, HTN.
! Wernicke-Korsakof...
Methamphetamine
! First synthesized by a Japanese
!
!
!
!

pharmacologist in 1893
Ephedrine most common precursor
Red phos...
Structures
! Phenethylamine

Source Undetermined

! Amphetamine
Source Undetermined

! Methamphetamine
Source Undetermined
Production
! Ephedrine

Source Undetermined

! Methamphetamine

Source Undetermined
Pathology
! Increase release of

!
!
!
!
!

neurotransmitters from nerve
terminals.
Serotinergic and dopaminergic ATP
decr...
Model of Methamphetamine Neurotoxicity

O2, H2O2, OH, NO
Bcl-2
DNA Damage
P53 Regulated Genes
Bax

Bax/Bcl-2
P53

Cytochro...
Source Undetermined
Signs and Symptoms
! Action phase

! Resolution phase

! Skin picking

! Exhaustion

! Head banging

! Fatigue

! Pacing

...
Other Signs and Symptoms
! Pulmonary hypertension
! Dyspnea
! Pleuritic chest pain
! Anorexia/weight loss
! Ulcers
! Rhabd...
TESS DATA
Methamphetamine Exposures Without Concomitants, 2001
(Cardiovascular Effects)
400
350
300
250
200
150
100
50

C
...
Methamphetamine and the ED
6 months UCDMC ED ending February 1997
461 methamphetamine (+) patients
Caucasian males without...
Methamphetamine and
Trauma
! UCDMC Level 1 Trauma Center
! Retrospective Study 1989 to 1994
! Results :
–  18,004 pts ; 3....
Methamphetamine and
Trauma
! Decrease in ethanol from 43 % to 35 %
! Meth (+) most common in Caucasian or

Hispanic
! Coca...
Treatment
!

Don’t forget to r/o other causes :
–  Look-alike diseases : e.g. Pheo,
scorpion bites.
–  Drugs : e.g. LSD, p...
Treatment (cont.)
! Control stimulant effects
! Decontamination
! Control hyperthermia : how ?
! Control seizures : how ?
...
What is Ecstasy (MDMA) ?
! 3,4-Methylenedioxymethamphetamine
! Sympathetic effects mild in low doses
! Potent releaser of ...
MDMA

Source Undetermined

Drug Enforcement Agency,
Wikimedia Commons
History of Ecstasy
! 1914

Patented as Appetite suppressant
!  Never Marketed

! 1970’s
! 1980’s
! 1990’s
! 2000
!

Use by...
Illicit Ecstasy Tablets

Drug Enforcement Agency, Wikimedia Commons
Pathology
! Similar to other amphetamines in

causing release of catecholamines.
! Alpha and beta-adrenergic agonist.
! Ca...
Effects
! DESIRED

! UNDESIRED

! Increased energy

! Jaw clenching

! Euphoria

! Paranoia

! Empathy

! Hot / cold flash...
Clinical Signs and Symptoms
! Rhabdomyolysis
! Hyponatremia
! DIC
! Renal failure
! Hepatotoxicity
! Aplastic anemia : rar...
Illicit MDMA Adulterants
! Assayed tablets have contained :
–  MDMA
–  MDMA with Caffeine
–  Dextromethorphan 122 to 143 m...
Treatment
! Similar to amphetamines and

derivatives
! Controlling cerebral edema from
hyponatremia important.
! Pneumomed...
Dextromethorphan : Case
Study …..
! 14 year old M ingested 30 Coricidin

tablets to get high. At 2.5 hours :
–  Lethargic,...
Dextromethorphan (DXMF)
Abuse
! Many DXMF containing OTC products

! Coricidin : many combinations
–  DXMF 30 mg, CTM, APA...
Dextromethorphan
! Therapeutic doses : mild CNS effects

! High doses : significant CNS effects
! Specific DXMF receptors ...
Dextromethorphan :
Treatment
! Gastrointestinal decontamination
! Narcan may be useful
! Supportive Care
! Laboratory
–  R...
Mescaline

Source Undetermined
Characteristics
! Derived from peyote cactus.
! Hallucinogen.
! Can mimic an acute gastroenteritis
Mescaline Treatment
! Supportive
Flunitrazepam
! Used throughout Europe.
! Not approved in the US.
! One of the “date-rape” drugs.
! By weight 10x more pot...
Flunitrazepam tablets

Drug Enforcement Agency, Wikimedia Commons

New Rohypnol tablets include a dye that
make the drug v...
Pathology
! A benzodiazapine working on the

GABAA receptor.
! Lipid soluble rapidly crossing the BB

barrier.
Effects
! “DESIRED”
!
!
!
!
!
!

Euphoria
Hallucinations
Disinhibition
SM relaxation
Sedation
Memory impairment

! UNDESIR...
Treatment
! Supportive care.

AC, lavage (use with caution, may be
contraindicated)
Benzodiazepine antagonists
(flumazenil...
Inhalant Abuse
! Freon Propellants
! Xylene, Toluene
! Gasoline Fumes

United States Department of Defense,
Wikimedia Comm...
Anticholinergic Abuse
! Antihistamines
! Jimson Weed
! Anticholinergic Syndrome:
–  Mad as a hatter
–  Blind as a bat
–  H...
Summary
! GHB / GHB Analogs
–  Classic Symptoms in Overdose
–  Withdrawal Symptoms
! Rave Parties
–  Multiple drugs common...
Summary
! Methamphetamine is a major problem
! Older drugs of abuse have not gone

away

–  PCP
–  LSD
–  Heroin
–  Cocain...
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GEMC: Drugs of Abuse: Resident Training

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This is a lecture by Dr. Jim Holliman and Dr. Tim Albertson from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.

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GEMC: Drugs of Abuse: Resident Training

  1. 1. Project: Ghana Emergency Medicine Collaborative Document Title: Drugs of Abuse Author(s): Tim Albertson, M.D., Ph.D. (University of California- Davis); Jim Holliman, M.D., F.A.E.C.P. (Pennsylvania State University) 2012 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for selfdiagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1
  2. 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair. 2
  3. 3. Update on Drugs of Abuse (“some club-drug stuff”) Tim Albertson, M.D.,Ph.D. Professor of Medicine, Pharmacology and Toxicology UC Davis School of Medicine CPCS, Sacramento Division Bearstache, Flickr Jim Holliman, M.D. Penn State University
  4. 4. Overview of Topics ! Gamma hydroxybutyrate (GHB) –  GHB –  GHB Analogs –  GHB / Analog Withdrawal ! Ecstasy : MDMA (Methylene dioxymethamphetamine)
  5. 5. Overview of Topics ! Methamphetamine ! Dextromethorphan (DM) ! Ketamine ! Flunitrazepam ! Mescaline ! Inhalants ! Anticholinergics
  6. 6. United States Department of Justice, Wikimedia Commons GHB (Gammahydroxybutyrate)
  7. 7. What is GHB? ! Gamma hydroxybutyrate ! Naturally occurring in brain tissue –  neurotransmitter-like substance –  dopamine release in substantia nigra ! Similar structure to GABA ! GABA-B agonist effects ! Approved for narcolepsy 2002 –  Sodium oxybate (Xyrem) Orphan Medical –  4.5 gms a night AWP $739 / month limited to certain pharmacies and physicians
  8. 8. GHB ! Investigated as an anesthetic agent : ! ! ! ! caused myoclonus and delirium ; current IND for sleep apnea Crystalline salt Soluble in water and methanol Tasteless GBL-gamma-butyrolactone & BD-1,4 butanediol precursor molecules convert to GHB in-vivo
  9. 9. Structure Activity Relationship COOH COOH CH2 CH2 CH2 CH2 CH2 CH2 OH GHB gamma hydroxybutyrate NH2 GABA gamma amino butyric acid
  10. 10. History of GHB ! 1960’s ! 1987 ! 1990-1 ! 1992-5 ! 1996 ! 1997 ! 2000 ! 2002 France - Synthesized as an Anesthetic Orphan Drug (IND-narcolepsy) ; USFDA Body Builders “Undetectable steroid” Growth hormone stimulator Sleep aid, Rave party, Popularity rises Sexual enhancer, “Date-Rape” Drug Emergence of GHB Analogs Emergence of Withdrawal Cases Federal Schedule I status FDA approval for Narcolepsy : Xyrem
  11. 11. Slang Names : Gamma Hydroxybutyrate ! Cherry meth ! Liquid E ! Easy lay ! Liquid X ! G, G caps ! Liquid ecstasy ! Gamma hydrate ! Natural sleep 500 ! Georgia home boy ! Organic Quaalude ! GHB ! Oxy sleep ! GH Beers ! Scoop
  12. 12. What are GHB Analogs? ! Organic solvents –  √-Butyrolactone, 2(3) Dihydrofuranone, –  1,4-Butanediol, Tetramethylene Glycol ! Converted to GHB in vitro or in vivo –  In vitro using NaOH, heat –  In vivo (Lactonase enzymes) : GBL –  In vivo (alcohol / aldehyde dehydrogenase) ! Identical clinical effects to GHB
  13. 13. Conversion : Gamma Butyrolactone (GBL) O GBL NaOH + H2O in vitro =O Lactonase In vivo C OOH CH2 CH2 CH2 OH GHB
  14. 14. Gamma Butyrolactone (GBL) United States Department of Justice, Wikimedia Commons
  15. 15. Slang Names : Gamma Butyrolactone or Dihydro Furanone ! Blue Nitro ! Invigorate ! Firewater ! Jolt ! Furanone Extreme ! Liquid Libido ! Gamma G ! Regenerize ! GBL ! ReneTrient ! GH Release ! Revivarant ! Insom-X ! Revivarant-G
  16. 16. Source Undetermined Renewtrient and Blue Nitro, GHB precursors, have been removed from the market.
  17. 17. Slang Terms : 1,4 Butanediol or Tetramethylene glycol ! Biocopia PM ! Thunder Nectar ! Borametz ! Pro G ! BVM ! Promusol ! Enliven ! Rest-eze ! FX ! Revitalize Plus ! NRG3 ! Serenity ! Inner G ! SomatoPro
  18. 18. Incidence : GHB and Precursors 400 356 350 C A S E S 300 250 232 199 200 150 89 100 50 0 18 10 34 9 19 105 37 1990 1991 1992 1993 1994 1995 1996 1997 SF POISON CONTROL CONTROL Source Undetermined 1997 1998 1999 CA POISON
  19. 19. Pathology ! Structurally similar to GABA ! Stimulates GABAB receptors ! Influences dopamine release from substantia nigra ! Readily crosses the BB barrier
  20. 20. GHB / Analogs : Clinical Presentation ! Vomiting, Coma, Bradycardia ! Myoclonic jerking ! Loss of protective airway reflexes –  Aspiration risk ! Hypothermia, Mild respiratory acidosis ! HOTN when combined with ethanol
  21. 21. Effects ! “DESIRED” ! UNDESIRED Euphoria Mood elevation Hallucinations GH-Muscle growth? ! Amnesia ! Decreased HR, ! ! ! ! RR ! Coma ! Excessive salivation ! Absence-like sz’s
  22. 22. Emergency Department (ED) Course of Gamma Hydroxybutyric Acid (GHB) Intoxication Study Acad Emerg Med 2002 Jul;9(7):730-9 Mason Study Intubated Duration Time in Number of ED if Not Admitted Intubation Admitted Chin et al. ( n = 88) 13 % 179 min NR 11 % Mahon et al. ( n = 8) 50 % 80 min NR 0% Li et al. ( n = 7) 57 % 210 min 360 min 43 % Garrison & Mueller ( n = 78) 10 % NR 180 min 4%
  23. 23. Case Study ….. ! 26 y/o F with chronic insomnia doubled her dose of Blue Nitro (GBL) : 3 oz. – Vomiting within 15 minutes – Pt was unresponsive within 30 minutes – Myoclonic jerking – EMS was called – VS: BP 120 / 70, HR 50, RR 22, T 35
  24. 24. Case Study continued …. ! Unresponsive to pain, GCS 3. ! CT scan normal, glucose 125 ! No response to naloxone or flumazenil ! Woke up within 4 hours ! Discharged ! Urine Toxicology screen negative
  25. 25. GHB / Analogs : Kinetics ! Onset 15 minutes –  Immediate conversion of analogs to GHB ! Coma ! ! ! ! within 30 minutes Peak 1 hour T 1/2 Short Duration 1 to 6 hours (Average 2.5 hr) Most patients require < 5 hr observation
  26. 26. Emergence Delirium ! Myoclonic jerking motions ! Confusion, agitation, combativeness –  Transient symptoms (< 30 minutes) –  Symptoms worsen with stimulation ! Treatment –  Supportive Care –  Minimize stimulation. “Back off”
  27. 27. GHB / Analogs : Diagnosis ! History of use and circumstances ! Clinical Presentation ! Short Duration ! Role of Laboratory –  Suspected assault –  Obtain sample within 12 hours –  National Medical Laboratories
  28. 28. GHB / Analogs : Treatment ! Supportive Care –  Approximately 35 % patients require airway protection ! Gastrointestinal Decontamination –  Limited Value –  Consider Charcoal in massive ingestions ! Education regarding Dependence
  29. 29. GHB Dependence : Case Study ! 29 year old male started taking GHB for the “anabolic effects” 2 yrs ago ! Gradually increased dose to 4 to 6 “capfuls” every 4 hours ! Discontinued the GHB cold turkey ! Arrived in ED 24 hr after his last dose
  30. 30. Case Study continued …. – Patient was highly agitated – Visual and auditory hallucinations – Delusional, paranoid – Tremulous, diaphoretic – VS: HR 110, BP 160 / 112, T 99.1
  31. 31. Case Study continued ... ! Patient received : –  Ativan : 90 mg in the first 24 hours –  Phenobarbital, Haloperidol ! 10 day withdrawal course ! Discharged symptom and drug free
  32. 32. GHB Withdrawal ! Similar to ETOH and sedative-hypnotic withdrawal. ! Symptoms start within a few hours of discontinuation. ! Seen with long-term use or daily use.
  33. 33. GHB Withdrawal : Clinical Presentation ! Onset : 1 to 6 hours ! Progression of sxs over 1 to 3 days ! Symptoms –  Agitation, hallucinations, paranoia –  Tremulous, diaphoretic –  Tachycardic, hypertensive –  Hyperthermia, Rhabdomyolysis possible ! Duration : 5 to 15 days
  34. 34. GHB Withdrawal : Management !   AGGRESSIVE TREATMENT EARLY ! Benzodiazepines ! High doses may be required ! Barbiturates ! Antipsychotics ! Unproven Therapy –  Baclofen (GABA-B agonist)
  35. 35. Stimulants of Abuse ! Methamphetamine ! Methylene dioxymethamphetamine : MDMA (Ecstasy) ! Cocaine ! Ketamine / PCP (phencyclidine) ! Dextromethorphan
  36. 36. Rave Party : Case Study ... ! 18 year old F was at a Rave party with a friend. She was drinking ethanol and using the following: –  Midnight –  3 am –  5 am 1 tablet of Ecstasy Snorted 1 line of Ketamine Drank a “capful” of GHB ! At 6:30 am patient found slumped in bathroom, cyanotic. EMS called.
  37. 37. Case Study continued …. ! ! ! ! In ED, comatose but not cyanotic. Intubated for airway protection. No response to flumazenil or narcan VS: HR 58, BP 110 / 60, RR 16, p 5mm, T 37 ! ICU admission. Woke up at 12 hours ! Extubated, discharged
  38. 38. Ketamine : Clinical Presentation ! Dissociative anesthetic ! Clinical Presentation –  Separation of perception and sensation –  Nystagmus, hallucinations, lethargy, sz –  tachycardia, HTN, RR depression –  hyperthermia ! Duration –  2 to 4 hours
  39. 39. Ketamine Treatment ! Supportive ! Sedation
  40. 40. Phencyclidine Effects ! Tremors, agitation, hallucinations : visual and auditory. ! Tachycardia, HTN. ! Wernicke-Korsakoff syndrome. Treatment is same as for ketamine
  41. 41. Methamphetamine ! First synthesized by a Japanese ! ! ! ! pharmacologist in 1893 Ephedrine most common precursor Red phosphorus-hydriotic acid most common reduction method. D-isomer : CNS stimulant effects. L-isomer : peripheral sympathomimetic activity.
  42. 42. Structures ! Phenethylamine Source Undetermined ! Amphetamine Source Undetermined ! Methamphetamine Source Undetermined
  43. 43. Production ! Ephedrine Source Undetermined ! Methamphetamine Source Undetermined
  44. 44. Pathology ! Increase release of ! ! ! ! ! neurotransmitters from nerve terminals. Serotinergic and dopaminergic ATP decrease. 5HT and D2 depletion. Apoptosis Endothelial injury. Reactive oxygen species.
  45. 45. Model of Methamphetamine Neurotoxicity O2, H2O2, OH, NO Bcl-2 DNA Damage P53 Regulated Genes Bax Bax/Bcl-2 P53 Cytochrome Release ROS Caspase Activation Terminal Degeneration Apoptosis Lena Carleton, University of Michigan
  46. 46. Source Undetermined
  47. 47. Signs and Symptoms ! Action phase ! Resolution phase ! Skin picking ! Exhaustion ! Head banging ! Fatigue ! Pacing ! Sleep ! Paranoid psychosis ! Depression ! Extreme suspiciousness
  48. 48. Other Signs and Symptoms ! Pulmonary hypertension ! Dyspnea ! Pleuritic chest pain ! Anorexia/weight loss ! Ulcers ! Rhabdomyolysis
  49. 49. TESS DATA Methamphetamine Exposures Without Concomitants, 2001 (Cardiovascular Effects) 400 350 300 250 200 150 100 50 C he s tp ai n (in H Ta ch yp er yc ar di a te cl . N ns on ion ca rd H E yp i a c C ) ot G en ch si an on ge (o C th ar er di ) ac ar C re on B st ra du dy ct ca io n rd di ia D st ys ur rh ba yt hm nc e ia D (o ys th rh er yt ) A hm sy st ia ol (v e ta ch /v fib ) 0 Source: American Association of Poison Control Centers Toxic Exposure Surveillance System, 2001
  50. 50. Methamphetamine and the ED 6 months UCDMC ED ending February 1997 461 methamphetamine (+) patients Caucasian males without health insurance Increase use of ambulances and acute hospitalization ! Significant association with trauma : blunt 33 % and penetrating 4 % ! Altered LOC (23 %), Abd pain (13 %), suicide (8 %), chest pain (8 %), skin infections (6 %) ! Richards, et al., West J Med 1999 ; 170:198-202 ! ! ! !
  51. 51. Methamphetamine and Trauma ! UCDMC Level 1 Trauma Center ! Retrospective Study 1989 to 1994 ! Results : –  18,004 pts ; 3.1 / 1000 population per year –  + methamphetamine defined as urine > 1000 ng / ml –  Rates increased from 7.4 to 13.4 % –  Cocaine rates 5.8 to 6.2 %
  52. 52. Methamphetamine and Trauma ! Decrease in ethanol from 43 % to 35 % ! Meth (+) most common in Caucasian or Hispanic ! Cocaine (+) most common African American ! Meth (+) in MVA or MCA’s ! Cocaine (+) in assaults, GSW’s or stab wounds ! Schermer and Wisner, J Am Coll Surg 1999; 189: 442-449
  53. 53. Treatment ! Don’t forget to r/o other causes : –  Look-alike diseases : e.g. Pheo, scorpion bites. –  Drugs : e.g. LSD, psilocybinhallucinations, etc. –  Elevated temperature : e.g. malignant hyperthermia, NMS, anticholinergic syndrome. –  Seizures : e.g. cocaine, ETOH withdrawal. –  CVS : e.g. GHB withdrawal.
  54. 54. Treatment (cont.) ! Control stimulant effects ! Decontamination ! Control hyperthermia : how ? ! Control seizures : how ? ! Be careful of physical restraints. ! Treat psychiatric conditions.
  55. 55. What is Ecstasy (MDMA) ? ! 3,4-Methylenedioxymethamphetamine ! Sympathetic effects mild in low doses ! Potent releaser of serotonin ! Overdose –  Symptoms similar to amphetamines –  Risk of serotonin syndrome –  Risk of hyponatremia ! SIADH and / or increased water intake
  56. 56. MDMA Source Undetermined Drug Enforcement Agency, Wikimedia Commons
  57. 57. History of Ecstasy ! 1914 Patented as Appetite suppressant !  Never Marketed ! 1970’s ! 1980’s ! 1990’s ! 2000 ! Use by psychiatrists “LSD of the 60’s” Increasing abuse, Rave party use Continuing abuse Illicit adulterants common
  58. 58. Illicit Ecstasy Tablets Drug Enforcement Agency, Wikimedia Commons
  59. 59. Pathology ! Similar to other amphetamines in causing release of catecholamines. ! Alpha and beta-adrenergic agonist. ! Can cause SIADH by an unclear mechanism.
  60. 60. Effects ! DESIRED ! UNDESIRED ! Increased energy ! Jaw clenching ! Euphoria ! Paranoia ! Empathy ! Hot / cold flashes ! Visual ! Hyperpyrexia hallucinations ! Seizures
  61. 61. Clinical Signs and Symptoms ! Rhabdomyolysis ! Hyponatremia ! DIC ! Renal failure ! Hepatotoxicity ! Aplastic anemia : rare
  62. 62. Illicit MDMA Adulterants ! Assayed tablets have contained : –  MDMA –  MDMA with Caffeine –  Dextromethorphan 122 to 143 mg / tablet –  Caffeine –  Ephedrine, Pseudoephedrine, PPA –  Placebo
  63. 63. Treatment ! Similar to amphetamines and derivatives ! Controlling cerebral edema from hyponatremia important. ! Pneumomediastinum also an issue ! Controlling hyperthermia predicts survival in several studies
  64. 64. Dextromethorphan : Case Study ….. ! 14 year old M ingested 30 Coricidin tablets to get high. At 2.5 hours : –  Lethargic, slurred speech, hallucinating – Flushed , tremulous – Nystagmus present – VS : HR 114, BP 170 / 100, T 97.8, p 7mm
  65. 65. Dextromethorphan (DXMF) Abuse ! Many DXMF containing OTC products ! Coricidin : many combinations –  DXMF 30 mg, CTM, APAP, PPA, etc. ! Teenage DXMF abuse is rising ! Easy OTC availability
  66. 66. Dextromethorphan ! Therapeutic doses : mild CNS effects ! High doses : significant CNS effects ! Specific DXMF receptors (opiate - sigma) ! Anticholinergic-like symptoms ! Hallucinations, delusion, dysphoria ! Opiate kappa and mu receptors ! Opiate effects
  67. 67. Dextromethorphan : Treatment ! Gastrointestinal decontamination ! Narcan may be useful ! Supportive Care ! Laboratory –  Rule out aspirin and acetaminophen
  68. 68. Mescaline Source Undetermined
  69. 69. Characteristics ! Derived from peyote cactus. ! Hallucinogen. ! Can mimic an acute gastroenteritis
  70. 70. Mescaline Treatment ! Supportive
  71. 71. Flunitrazepam ! Used throughout Europe. ! Not approved in the US. ! One of the “date-rape” drugs. ! By weight 10x more potent than diazepam. ! Produces effects within 15 mins.
  72. 72. Flunitrazepam tablets Drug Enforcement Agency, Wikimedia Commons New Rohypnol tablets include a dye that make the drug visible if slipped into a drink
  73. 73. Pathology ! A benzodiazapine working on the GABAA receptor. ! Lipid soluble rapidly crossing the BB barrier.
  74. 74. Effects ! “DESIRED” ! ! ! ! ! ! Euphoria Hallucinations Disinhibition SM relaxation Sedation Memory impairment ! UNDESIRED ! Hypotension ! Drowsiness ! Apnea ! Urinary retention ! Tremors
  75. 75. Treatment ! Supportive care. AC, lavage (use with caution, may be contraindicated) Benzodiazepine antagonists (flumazenil) : NO!! (very few indications).
  76. 76. Inhalant Abuse ! Freon Propellants ! Xylene, Toluene ! Gasoline Fumes United States Department of Defense, Wikimedia Commons
  77. 77. Anticholinergic Abuse ! Antihistamines ! Jimson Weed ! Anticholinergic Syndrome: –  Mad as a hatter –  Blind as a bat –  Hot as Hades –  Dry as a bone –  Red as a beet
  78. 78. Summary ! GHB / GHB Analogs –  Classic Symptoms in Overdose –  Withdrawal Symptoms ! Rave Parties –  Multiple drugs commonly used ! Rising OTC Dextromethorphan Use –  Rule out aspirin and acetaminophen
  79. 79. Summary ! Methamphetamine is a major problem ! Older drugs of abuse have not gone away –  PCP –  LSD –  Heroin –  Cocaine –  Ethanol –  Marijuana

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