A Symbiotic Relationship Between theToxicologist

and the World of Numerology

D. AndersonLos Angeles County Dept. of Coroner

CAT/SAT May, 2003

Toxicologist

! Postmortem & Antemortem• Analysis of Biological specimens for the

presence of drugs and/or poisons.– Specimens

• Postmortem: Many possibilities• Antemortem: Blood, Urine or other

! Interpretation• Attempt of an assignment of behavior• Cause/effect relationship

What is Numerology?! The study of the symbolism of numbers! History

• Some 10,000 years ago– Egypt and Babylonia used numbers for calculations– Foundation of modern mathematics

! Modern Day• Provides significant information on people’s

personalities and character. ! Toxicologist

• Assignment of a meaning to the quantitation performed

Merging of the Two!Numerology and Toxicology

• Heart Blood vs Femoral Blood Levels– Obviously there’s a difference!– Redistribution going on!

!Comparison to already established values– Literature

• Journals: JAT, JFS, etc.• Winek• Baselt

– Laboratory• Establish your own values!

Merging of the Two!Liver Levels

• Acute vs Chronic• Agrees or disagrees with the “supposed”

blood sample

!Gastric Levels• Suicide or Accident• More Information needed!• Will the pathologist believe you?

Life as a Toxicologist !(Theoretically Speaking)

Knowledge is Bliss!

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And You Thought you Knew Something?

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In-House Drug Study

!Duragesic - Fentanyl

Fentanyl

! Short duration of action! Synthetic Phenylpiperidine derivative related

to meperidine! 50-100 x more potent than morphine! Administration

• Sublimaze– Injectable form

• Duragesic– Transdermal Patch

Fentanyl-Duragesic! Distributed by Janssen Pharmaceuticals! Doses per every 72 hours:

• 25 ug/hr 2.5 mg fentanyl• 50 ug/hr 5.0 mg fentanyl• 75 ug/hr 7.5 mg fentanyl• 100 ug/hr 10 mg fentanyl

C22H28N2OMW=336.5

Fentanyl-Duragesic

! Symptoms• CNS: Analgesia and Sedation• Severe respiratory depression

– Muscle rigidity, seizures, coma and hypotension

! Serum concentrations undetectable for 2 hrs, rise gradually for 12-14 hrs. • Steady state reached within 24 hours

– 25 ug/hr 0.30 - 1.2 ug/L– 50 ug/hr 0.60 - 1.8 ug/L– 75 ug/hr 1.1 - 2.6 ug/L– 100 ug/hr 1.9 - 3.8 ug/L

Fentanyl-Duragesic

! Pharmacodynamics• Loss of consciousness: 34 + 7 ug/L

• Respiratory depression: 1-5 ug/L

• Minimal effective concentration to produce an analgesic effect: 0.63 + 0.25 ug/L

Twenty-five Postmortem Cases involving Duragesic®

! Three Year Study- Fentanyl Patch Application! Demographics

• 18 males, 7 females • Ages 19-84, average age 46 years

! Modes of Death• 15 Accidental• 5 Naturals• 3 Suicides• 2 Undetermined

Duragesic®-Summary by modeTwenty-five Postmortem Cases

! Accidents: 15 cases• Heart Blood Range 35-139 ug/L (14)• Femoral Blood Range 4.5-43 ug/L (10)

• 9 cases: Fentanyl directly related to cause of death – Heart Blood Range 6.4-139 ug/L (8)– Femoral Blood Range 4.5-43 ug/L (6)

• 6 cases: Fentanyl was considered a non-factor– Heart Blood Range 3.7-22 ug/L (6)– Femoral Blood Range 6.8-19 ug/L (4)

Duragesic®-Summary by mode Twenty-five Postmortem Cases

! Naturals: 5 cases• Heart Blood Range 1.8-81 ug/L (5)• Femoral Blood Range 3.1-24 ug/L (2)

! Suicides: 3 cases• Heart Blood Range 6.3-29 ug/L (2)• Femoral Blood Range 6.5 ug/L (1)

! Undetermined: 2 cases• Heart Blood Range <2.0-2.6 ug/L (2)

Duragesic®-Recovered PatchesTwenty-five Postmortem Cases

! 18 cases! Recovered Patches Heart Bld Fem. Bld (ug/L)

• 1 patch (10) 1.8 - 139 7.9 - 43• 2 patches (6) 3.5 - 81 3.1 - 19• 6 patches (1) 34 19• 11 patches (1) 29 -----

! Conclusion ?????

Duragesic®-Conclusions Twenty-five Postmortem Cases

! Non-fentanyl related deaths: 10 cases • Heart Blood Range <2.0-7.0 ug/L (9)• Femoral Blood Range 3.1-7.9 ug/L (4)

NOTE: Apparent minimal redistribution! Multiple-drug related deaths-Fentanyl contributing

factor: 11 cases • Heart Blood Range 12-139 ug/L (9)• Femoral Blood Range 12-43 ug/L (5)

NOTE: Apparent redistribution occurs as heart blood concentrations increase

Duragesic®-Conclusions Twenty-five Postmortem Cases

! Four Interesting Cases that did not fit the Retrospective analysis• 2 Cases involving Cancer Patients

– Heart blood levels 22 & 47 ug/L– Femoral blood levels 19 & 24 ug/L

Tolerance to fentanyl?• 2 Other Cases

– Heart blood levels 6.4 & 81 ug/L– Femoral blood level 4.5 ug/L – COD: Acute Fentanyl Intoxication-Accident ?

Atherosclerotic cardiovascular disease-Natural ?

Duragesic® Published Literature

! Edinboro, et al., 1997• 83 year old cancer patient• Heart Blood 25 ug/L 3- 100 ug/hr patches• COD: Fentanyl Overdose MOD: Undetermined

! Flannagan, et al., 1996• 31 year old funeral home worker• Heart Blood 15 ug/L 1- 75 ug/hr patch

1- 100 ug/hr patch• COD: Fentanyl poisoning

Duragesic®

!Discussion• Better investigations and complete histories are

necessary to interpret any postmortem levels.

• Postmortem fentanyl levels following therapeutic use ranges to 7.0 ug/L in Heart blood.

• Postmortem redistribution is minimal

Game Time

!Lets Play

Interpretation!

Case Study

! 47 year-old female (66 inches, 139 lbs)• Unresponsive in motel room

• History of chronic back pain

• Reportedly with suicidal ideation

Fentanyl Case Study

!Autopsy• No fatal trauma

• Pulmonary edema and congestion

• 18 “Duragesic” patches on chest and back

Patch Lady

!Toxicology Results

! Interpretation?

Heart Blood Femoral Blood LiverFentanyl 85 ng/ml 70 ng/ml 540 ng/g

Methamphetamine 1.5 ug/ml --- ---Amphetamine ND --- ---

Patch Lady

!Cause and Manner of Death?

Another Fentanyl Case

! 56 year old male (130 lbs, 69 inches)

! Slumped in drivers seat of his car-parked in driveway

!Duragesic patch on upper right arm

Another Fentanyl Case

!Toxicology

! Interpretation?

Central Blood (ng/ml) Femoral Blood (ng/ml)Fentanyl 15 8.5

Another Fentanyl Case

!Cause and Manner?

!Switching Gears

Cocaine! 31 year-old Male (66 inches, 211 lbs)

• 0000 hrs: drinking heavily and throwing up• Unresponsive in residence living room at 0230

hrs• Long history of cocaine abuse• History of suicidal ideations• Recently lost job as armed security guard

Mr. Coke Head

!White powdery substance • Wrapped in a paper envelope on windowsill of

living room!¾ Empty bottle of brandy seen on kitchen

counter! Suicide note NOT present

Mr. Coke Head

!Toxicology Results

! Interpretation?

Heart Bld (ug/ml) Femoral Bld (ug/ml)Cocaine 0.33 1.2Benzoylecgonine 13 14

Mr. Coke Head

!Cause and Manner of Death??

Other Cocaine CasesCase #2

! 42 year old male! Found unresponsive on Apartment Floor!No drug paraphernalia recovered!No trauma noted!No history available

Toxicology

! Interpretation?

Heart Bld (ug/ml) Femoral Bld (ug/ml)Cocaine 81 15Benzoylecgonine 30 19Cocaethylene 0.83 0.37

Case #2

!Cause and Manner of Death?

Case #3

! 36 year old male!Apparent Natural Death!Died at hospital and transported to Mortuary!Attending Physician refused to sign DC!Coroner Jurisdiction

Case #3

!Toxicology

! Interpretation?

Heart Bld (ug/ml) Femoral Bld (ug/ml)Cocaine ND NDBenzoylecgonine 8.8 8.5Cocaethylene ND ND

Case #3

!Cause and Manner?

!Do you think your getting pretty good at this

interpretation stuff?

Last Coke Case

! 57 year old male!Unspecified heart problems!Respiratory concerns and diabetes!Handicapped

• Obese (370 lbs)• Uses electric cart for mobility• Unresponsive in house

Case #4

!Toxicology

! Interpretation?

Heart Bld (ug/ml) Femoral Bld (ug/ml)Cocaine 1.1 1.1Benzoylecgonine 9.4 11Cocaethylene ND ND

You’re Getting Good!

! Accidental Overdose ?• Cocaine Intoxication

A Very Interesting Case Study

!Early December, 2000!Decedent

• 34 year old male found unresponsive in hallway of his home

• Exclusive Pasadena area • Blunt force trauma to the head• Bruises and Abrasions to the arms

Who Dun-it Case Study?

!History of Decedent• Ex-Jockey

– Winner of the 1991 & 1999 Kentucky Derby

– Christopher W. Antley• Heavily into drugs and alcohol• Living as a recluse

– Friends constantly checking in – Bringing meals

Jockey-Boy! Scene Description

• Single family residence• Decedent found in hallway between kitchen and

bedrooms• Blood spatter on the floor and walls throughout the

hallway– Appears that the decedent was crawling around

• Bedroom in a disarray– Door ripped off hinges– Does not appear to be a robbery

• Drawers, closets and cabinets are closed

Jockey-Boy

!Clothing• Shirt covered in blood splotches• Pants covered in blood

!Toilet paper (bloody) resting by his head• As if he attempted to blot his head injury

Jockey-Boy

! Obvious struggle throughout the home per investigation.

! Moded as Homicide per responding Officers, Investigating Detectives, and Coroner’s Investigator

! Ex-employee/roommate named as prime suspect

Jockey-Boy!Autopsy

• Forehead: Large hematoma• Small puncture to the top of the scalp• Arms

– Elbow• Large round abrasion and bruising

– Forearm• Bruises • Defensive wounds from “warding off blows”

! NO OBVIOUS Anatomical Cause of Death

Jockey-Boy! Pathologist re-visits the scene with the

Coroner Investigator

!Collects multiple pills and medication throughout bedroom

Jockey-Boy

! Pended for Toxicological Studies• Blood

– Heart and Femoral

• Liver• Gastric Contents• Liver• Vitreous• Urine• Bile

Jockey-Boy! Toxicology

• Heart Blood – Ethanol– Cocaine & Metabolites– Opiates– Barbiturates Not Detected– Phencyclidine– Marijuana– Methamphetamines– Bases Positive– Acid/Neutral Drugs

Jockey-Boy! Toxicology

! Cause of Death established??

Heart Blood Femoral Blood Liver Gastric (mg total) UrineAmphetamine 3.1 1.3 15 0.22 2.0Methamphetamine 0.84 0.50 2.6 0.12 4.8Pharmaceutical (Bases)

Paroxetine 1.0 0.32Propranolol 1.7 0.73

Acid/NeutralsCarbamazepine 20 21

Drug Concentrations (ug/ml or ug/g)

Jockey-Boy

! Paroxetine-Antidepressant• Redistribution

– Heart 1.0 ug/ml vs Femoral 0.32 ug/ml

! Propranolol-Heart Medication• Redistribution

– Heart 1.7 ug/ml vs Femoral 0.73 ug/ml

!Carbamazepine– Therapeutic concentrations

• Heart 20 ug/ml vs Femoral 21 ug/ml

Jockey-Boy

!Amphetamine and Methamphetamine• Interpretation

– Ingestion of Amphetamine?– Ingestion of Methamphetamine?– Ingestion of Amp. and Methamp.?– Ingestion of a drug breaking down to Amp.? – Ingestion of drug breaking down to Amp. and

ingestion of Methamp.?

Heart Blood Femoral Blood Liver Gastric (mg total) UrineAmphetamine 3.1 1.3 15 0.22 2Methamphetamine 0.84 0.5 2.6 0.12 4.8

Drug Concentrations (ug/ml or ug/g)

Clobenzorex!Elution Order

• PCP, Doxylamine, Tramadol, CLOBENZOREX, Chlorpheneramine, Metoprolol

Clobenzorex

! Clobenzorex Hydrochloride• C16H18ClN-HCl

– Formula weight 296.2– Molecular weight 259.5

• Manufactured by Hoechst Marion Roussel– 30 mg Capsule– Dark/light green in color– Marked with HMR– Distributed in Mexico

• Metabolizes to d-amphetamine

Jockey-BoyClobenzorex

! Symptoms• 20 times less potent than Amphetamine• Similar to other sympathomimetic amines

– Drug mouth– Excitation– Increase alertness/difficulty in sleeping

Clobenzorex

!Drug Standard Powder

• Dr. John T. Cody, Texas

Jockey-Boy

!Toxicology

! Final Interpretation

Heart Blood Femoral Blood Liver Gastric (mg total) Urine BilePharmaceutical (Bases)

Clobenzorex 1.9 QNS 174 4.9 1.3 14

Drug Concentrations (ug/ml or ug/g)

Jockey-Boy

!Final cause of death?

Conclusion

!Combining Toxicology and Numerology• Experience• In-house studies• Literature

!Use your Network of Resources