UNIVERSITY OF CALIFORNIA EVOLUTIONARY FORCES AT WORK IN THE HUMAN A dissertation submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY The Dissertation of Sol Katzmanis approved: Professor David Haussler, Chair Professor Kevin Karplus Professor Nader Pourmand Professor Alan Zahler Tyrus MillerVice Provost and Dean of Graduate Studies
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POISONS HAVE BECOME THE LEADING CAUSE OF ACCIDENTAL DEATHPolypharmacy Internet Designer Drugs Chemicals are legal until legislated as illegalChemists in Eastern Europe and Russia are employed High school kids can buy on the internet "Legal" drugs for sale at the corner store Old friends like Methamphetamine and Cocaine are still around SOURCES OF TEEN DRUGS EROWIDDOCUMENTING THE COMPLEX RELATIONSHIP BETWEEN HUMANS AND PSYCHOACTIVES The Pusher Man
Teen source of bad drug abuse information
E.g. DXM Jello recipe
PreRx with dramamine 200mg DXM in agar with vodka Advertised: Minimal vomiting/maximal existential insight Liberal prescribing Poor medicine cabinet accounting Parental inattentiveness
"legal" chemicals Cannabinoid Agonists JWH018, K2, Spice CB2 > CB1 receptor affinity MDMA, Methamphetamine, 2CE Dopaminergic/Serotonergic/Noradrenergic Reuptake inhibitors BromodragonFly Some presynaptic release Mephedrone, methedrone Serotonin Reuptake Benzylpiperazines BZP, TFMPP Tryptamines Psilocybin, LSD, DMT
Mountain in India
Some MJ screens will not show +
Patients are scared and have a high heart rate
Who knows what you buy on the Internet!
Blueberry Spice- renal failure
STRUCTURAL RELATIONSHIPS Alpha PVP 40 AM2201 24 AKB 48 2 IOWA IN AUGUST 2012 JWH081 3 JWH122 10 JWH203 3 JWH210 3 JWH250 1 MAM2201 3 MDPV 11 4-MEC 3 5-MeODALT 4 5-MeoDIPT 2 4-MePPP 5 Methylone 3 25I-NBOME 1 Pentedrone 10 TFMPP 4 UR144 25 URB754 3 XLR11 48 BREAKING BAD-STILL A PROBLEM The Drug of the new millenium Speed, Meth, Crank, Ice, Crystal, GlassEasy to synthesize Horribly addicting stimulant when abused Long duration of actionPrescription forms used for ADHD Entrepreneurs on the school bus MDMA 3,4-
2C-E, 2C-B, 2C-P, DOC, DOI Ecstasy, The Love drug
Bromo-DragonFLY- multiple fatalities in OK- sold as 2C-E Disorientation followed by a rush then happy sociability
Benzylpiperazine (BZP) – identified at autopsy Crash with confusion, depression, anxiety
Crash may last for weeks
16 y/o took a single tablet at school
Driving home and had a low speed collision with a phone
Found by EMS with jaw clenched and started having
Comatose for 18 hours in ICU
Stimulant effects like methamphetamine including seizures/hyperthermia Hallucinations and agitation resembling paranoid schiophreniaSpeech and Parkinsonian effects like serotonin syndrome 18 year old was with friends and started acting like "the bad guys" were coming.
Given benzos in ER. Hypertensive, tachycardia. Got intubated X 24 hours.
Tox screen negative. Was still acting paranoid and crazy after extubation.
Transferred to psych for 4 days and considered Paranoid Schizophrenic.
Suddenly cleared and admitted to smoking some stuff a friend had given him. Bromo DragonFly / MDPV / mCPP / ??? 4-Fluoroamphetamine XLR 11-aminoalkylindole UR 144-aminoalkylindole 25I-NBOMe (phenethylamine) 25B-NBOMe (phenethylamine) 2C-C-NBOMe (phenethylamine) Methoxetamine (arylcyclohexylamine) N,N-Dially-5-Methoxytryptamine (5-Methoxy-Dalt) (tryptamine) 2, 5 Dimethoxy-4-chloroamphetamine (phenethylamine/amphetamine) URB 754 (2-arachidonoyl glycerol)1 Phenazepam (benzodiazepine) No antidote or specific recommendations Not likely to identify toxin during hospitalization Khat bush
Benzos Benzos Benzos Aggressive management of seizures and hyperthermia For continued agitation/confusion/hallucinations, atypical antipsychotic such as Has morphed
Cyproheptadine for serotonin syndrome (?) Marketed as Bath Salts
BATH SALTS EXPOSURES REPORTED TO THE TEXAS POISON CENTER BATH SALTS- BEYOND BED AND BATH NETWORK DURING 1/1/10-7/12/11 Sold on the internet Smoke it, drink it, insufflate it, any orifice.
Legal until its illegal.
Derivatives like crazy.
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Taken by mouth is used to treat heroin addiction
Taken IV is very lethal
Variable pharmacogenetics- therapeutic to toxic in same dose range
100 fold variability?
Being replaced by Suboxone (buprenorphine/naloxone) to avoid diversion
Phenergan with Codeine Shows up in many autopsies
Killers, OC, OXY, Oxycotton
DXM, Dex, Skittles, Rob, DM Sustained release form of oxycodone
Cough suppressant in many OTC cough meds Very safe- unless crushed
Has opiate and hallucinatory properties Large dose intended to last all day
Many strange concoctions to concentrate and abuse Opiate for pain control
Lethal when injected
Can stop respirations, cause seizures Has insoluble excipients-pulmonary emboli
Combination of submission and amnesia
Date Rape Drug
Amnesia may be profound
Potent Benzo available in Mexico
Difficult to understand unless you see the level of anesthesia
Usually a group of drugs called "benzos" or benzodiazepines.
Flunitrazepam = Rohypnol
Synergistic with Alcohol and tasteless
Message of "The Hangover" should have been:
Don't trust a dealer and don't trust your
TO PEE OR NOT TO PEE? Urine Drug Screens in the home now readily available
Workplace: Highly Regulated/Highly Accurate
Require confirmation usually GC/MS Sally D or Sage of the Diviners
Home versions may miss some narcotics (oxy), show PCP for DXM, Meth
Herb in the sage family from Oaxaca
for Cold Meds, TCA's for Benadryl
Used in a religious context Will not show GHB, hallucinogens, plants
Hallucinogen-but not a fun one!
Second hand or Passive MJ will not show.
Rapidly being outlawed
If + pretty accurate that it is real MJ may show + for 6 weeks after heavy use
Many disappointed dopehead job seekers Read the instructions
What is the wisdom of doing this?
Not a substitute for conversation
Copyright 2004 by the Genetics Society of America Combining Mathematical Models and Statistical Methods to Understand and Predict the Dynamics of Antibiotic-Sensitive Mutants in a Population of Resistant Bacteria During Experimental Evolution Leen De Gelder,* Jose´ M. Ponciano,† Zaid Abdo,† Paul Joyce,† Larry J. Forney* and Eva M. Top*,1