Download OUT MY BACK DOOR PARACELSUS SAID

OUT MY BACK DOOR
AMBIEN AND DRIVING
WHAT IS ALLTHE CLAMOR ABOUT
John J. Treuting, Ph.D.
CAT Winter Meeting
February 5, 2008
Redondo Beach, CA
PARACELSUS SAID
“ALL SUBSTANCES ARE
POISONS; THERE IS NONE
WHICH IS NOT A POISON. THE
RIGHT DOSE DIFFERENTIATES
A POISON FROM A REMEDY.”
TEXAS CHILI COOK-OFF
CHILI #1 MIKE’
MIKE’S MANIAC MOBSTER MONSTER CHILI
JUDGE #1-- LITTLE TOO HEAVY ON THE
TOMATO. AMUSING KICK
JUDGE #2—NICE, SMOOTH TOMATO
FLAVOR. VERY MILD
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #1 MIKE’
MIKE’S MANIAC MOBSTER MONSTER CHILI
CHILI #2 ARTHUR’
ARTHUR’S AFTERBURNER CHILI
JUDGE #3 (FRANK)—HOLY CRAP, WHAT
THE HELL IS THIS STUFF? YOU COULD
REMOVE DRIED PAINT FROM YOUR
DRIVEWAY. TOOK ME TWO BEER TO
PUT THE FLAMES OUT. I HOPE THAT’S
THE WORST ONE. THESE TEXANS ARE
CRAZY.
JUDGE #--SMOKY, WITH A HINT OF
PORK. SLIGHT JALAPENO TANG.
JUDGE #2—EXCITING BBQ FLAVOR,
NEEDS MORE PEPPERS TO BE TAKEN
SERIOUSLY.
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #2 ARTHUR’
ARTHUR’S AFTERBURNER CHILI
CHILI #3 FRED’
FRED’S FAMOUS BURN DOWN THE BARN CHILI
JUDGE #3 (FRANK)—KEEP THIS OUT OF THE
REACH OF CHILDREN. I’M NOT SURE WHAT
I’M SUPPOSED TO TASTE BESIDE PAIN. I
HAD TO WAVE OFF TWO PEOPLE WHO
WANTED TO GIVE ME THE HEIMLICH
MANEUVER. THEY HAD TO RUSH IN MORE
BEER WHEN THY SAW THE LOOK ON MY
FACE.
JUDGE #1--EXCELLENT FIREHOUSE CHILI.
GREAT KICK. NEEDS MORE BEANS
JUDGE #2—A BEAN LESS CHILI, A BIT SALTY,
GOOD USE OF PEPPERS.
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #3 FRED’
FRED’S FAMOUS BURN DOWN THE BARN CHILI
CHILI #4 BUBBA’
BUBBA’S BLACK MAGIC
JUDGE #3(FRANK)—CALL THE EPA. I’VE
LOCATED A URANIUM SPILL. MY NOSE
FEELS LIKE I HAVE BEEN SNORTING
DRANO.EVERYONE KNOW THE ROUTINE BY
NOW. GET ME MORE BEER BEFORE I
IGNITE! BARMAID POUNDED ME ON THE
BACK, NOW MY BACKBONE IS IN THE
FRONT OF MY CHEST. I’M GETTING SHITFACED FROM ALL OF THE BEER.
JUDGE #1-- BLACK BEAN CHILI WITH ALMOST
NO SPICE. DISAPPOINTING.
JUDGE#2—HINT OF LIME IN THE BLACK
BEANS. GOOD SIDE DISH FOR FISH OR
OTHER MILD FOODS, NOT MUCH OF A
CHILI.
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #4 BUBBA’
BUBBA’S BLACK MAGIC
CHILI #5 LINDA’
LINDA’S LEGAL LIP REMOVAL
JUDGE #3 (FRANK)—I FELT SOMETHING
SCRAPING ACROSS MY TONGUE, BUT WAS
UNABLE TO TASTE IT. IS IT POSSIBLE TO
BURN OUT TASTE BUDS? SALLY, THE
BARMAID, WAS STANDING BEHIND ME WITH
FRESH REFILLS. THAT 300 POUND WOMAN
IS STARTING TO LOOK HOT, JUST LIKE THIS
NUCLEAR WASTE I’M EATING! IS CHILI AN
APHRODISIAC?
JUDGE #1--MEATY, STRONG CHILI. CAYENNE
PEPPERS FRESHLY GROUND, ADDING
CONSIDERABLE KICK. VERY IMPRESSIVE.
JUDGE #2—CHILI USING SHREDDED BEEF,
COULD USE MORE TOMATO. MUST ADMIT
THE CAYENNE PEPPERS MAKE A STRONG
STATEMENT.
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #5 LINDA’
LINDA’S LEGAL LIP REMOVAL
CHILI #7 SUSAN’
SUSAN’S SCREAMING SENSATION CHILI
JUDGE #3 (FRANK)—
(FRANK)—MY EARS ARE RINGING, SWEAT
IS POURING OFF MY FOREHEAD AND I CAN NO
LONGER FOCUS MY EYES. I FARTED AND FOUR
PEOPLE BEHIND ME NEEDED PARAMEDICS. THE
CONTESTANT SEEM OFFENDED WHEN I TOLD HER
THAT HER CHILI HAD GIVEN ME BRAIN DAMAGE.
SALLY SAVED MY TONGUE FROM BLEEDING BY
POURING BEER DIRECTLY ON IT FROM THE
PITCHER. I WONDER IF I’I’M BURNING MY LIPS OFF.
JUDGE #1-A MEDIOCRE CHILI WITH TOO MUCH
#1--A
RELIANCE ON CANNED PEPPERS.
JUDGE #2—
#2—HO HUM, TASTES AS IF THE CHEF
LITERALLY THREW IN A CAN OF CHILI PEPPERS AT
THE LAST MOMENT. I SHOULD NOTE THAT I AM
WORRIED ABOUT JUDGE #3. HE APPEARS TO BE IN
A BIT OF DISTRESS AS HE IS CURSING
UNCONTROLLABLY.
TEXAS CHILI COOK-OFF
TEXAS CHILI COOK-OFF
CHILI #7 SUSAN’
SUSAN’S SCREAMING SENSATION CHILI
CHILI #7 SUSAN’
SUSAN’S SCREAMING SENSATION CHILI
JUDGE #3(FRANK)—YOU COULD PUT A
GRENADE IN MY MOUTH, PULL THE PIN,
AND I WOULDN’T FEEL A THEIN. I’VE LOST
SIGHT IN ONE EYE, AND THE WORLD
SOUNDS LIKE IT IS MADE OF RUSHING
WATER. MY SHIRT IS COVERED WITH CHILI,
WHICH SLID UNNOTICED OUT OF MY
MOUTH. MY PANTS ARE FULL OF LAVA-LIKE
CRAP TO MATCH MY SHIRT.
AT LEAST DURING THE AUTOPSY, THEY’LL
KNOW WHAT KILLED ME. I’VE DECIDED TO
STOP BREATHING, IT’S TOO PAINFUL.
SCREW IT; I’M NOT GETTING ANY OXYGEN
ANYWAY. IF I NEED AIR, I’LL JUST SUCK IT
IN THROUGH THE 4-INCH HOLE IN MY
STOMACH.
AMBIEN AND DRIVING
TEXAS CHILI COOK-OFF
CHILI #8 TOMMY’
TOMMY’S TOETOE-NAIL CURLING CHILI
WHAT IS ALLTHE CLAMOR ABOUT
JUDGE #1-#1-- THE PERFECT ENDING, THIS IS A NICE
BLEND CHILI. NOT TOO BOLD, BUT SPICY ENOUGH
TO DECLARE IT’
IT’S EXISTENCE.
John J. Treuting, Ph.D.
JUDGE #2–
#2– THIS FINAL ENTRY IS A GOOD, BALANCED
CHILI. NEITHER MILD NOR HOT. SORRY TO SEE
THAT MOST OF IT WAS LOST WHEN JUDGE #3
PASSED OUT, FELL OVER AND PULLED THE CHILI
POT DOWN ON TOP OF HIMSELF. POOR DUD,
WONDER HOW HE’
HE’D HAVE REACTED TO REALLY
HOT CHILI.
CAT Winter Meeting
February 5, 2008
Redondo Beach, CA
NEWS FLASHES ABOUT AMBIEN
AMBIEN SUCCESS
“POPULAR
SLEEP AID COULD CAUSE LITTLE
KNOWN SIDE EFFECTS”
‘SLEEPDRIVING’ WREAKING HAVOC ON
ROADS
“DRIVING, OTHER ERATIC BEHAVIORS
REPORTED AFTER TAKING ZOLPIDEM”
MOST POPULAR INSOMNIA
MEDICATION IN THE USA
„ MANUFACTURED BY FRENCH
FIRM SANOFI-AVENTUS
„ MORE THAN 26 MILLION RX SOLD
LAST YEAR
„
CHEMICAL STRUCTURE OF
AMBIEN
INDICATIONS FOR USE
ZOLPIDEM IS USED IN THE
TREATMENT OF INSOMNIA
CHARACTEREIZED BY
DIFFICULTIES WITH SLEEP
ONSET AND/OR SLEEP
MAINTENANCE
DOSAGE FORMS AND
STRENGTHS
TABLET, AS TARTRATE
5MG, 10 MG
CR TABLETS(EXTENDED RELEASE)
6.25 MG (PINK)
12.5 MG (BLUE)
DOSAGE & ADMINISTRATION
THE RECOMMENDED DOSE FOR
AMBIEN CR IS 12.5 MG ONCE
DAILY IMMEDIATELY BEFORE
BEDTIME AND SHOULD NOT
EXCEED 12.5 MG PER DAY
Pharmacokinetics and
Pharmacodynamics
MECHANISM OF ACTION
(PHARMACODYNAMICS)
Dose of drug
administered
ABSORPTION
Drug concentration
in systemic circulation
DISTRIBUTION
Drug in tissues
of distribution
PHARMACOKINETICS
ELIMINATION
Drug metabolized or excreted
Drug concentration
at site of action
Pharmacologic Effect
PHARMACODYNAMICS
GABA A receptor agonist
„ Binds to receptors containing an
a1 subunit
„ shortens sleep latency and
prolongs total sleep time
„
Clinical response
Toxicity
Efficacy
PHARMACOKINETIC PROFILE
OF AMBIEN
RAPID ABSORPTION FROM THE GI
TRACT
„ SHORT ELIMINATION HALF-LIFE
(T ½ ) OF 2.2 HOURS IN HEALTHY
SUBJECTS
„ NO ACTIVE METABOLITES
„
CLINICAL TRIALS
BLOOD CONCENTRATIONS
SINGLE DOSES (PEAK)
5MG
10 MG
15 MG
20 MG
60 NG/ML @ 1.6 HRS
120 NG/ML @ 1.6 HRS
200 NG/ML @ 1.5 HRS
230 NG/ML @ 2.1 HRS
THERAPEUTIC RANGE: < 250 NG/ML
COMMON SIDE EFFECTS
„ DROWSINESS
EFFECTS ON DRIVING
(CNS DEPRESSANT)
„ IMPAIRED
COORDINATION
„ IMPAIRED
REACTION TIME
„ IMPAIRED
COGNITIVE SKILLS
„ DIZZINESS
„ LIGHTHEADEDNESS
„ DIFFICULTY
WITH
COORDINATION
DRUG RECOGNITION
EVALUATION
HGN
PRESENT
VGN
PRESENT (HIGH DOSES)
LOC
PRESENT
PUPIL SIZE
NORMAL
PULSE DOWN
BLOOD PRESSURE DOWN
BODY TEMPERATURE NORMAL
METHODS OF
ANALYSIS
„
ELISA
„
GAS CHROMATOGRAPHY
LITERATURE CITATIONS
LITERATURE CITATIONS
LIDDICOAT, L. AAFS, 2006
DISCUSSED 6 CASES OF IMPAIRED
DRIVING RELATED TO ZOLPIDEM
LEVELS RANGED FROM 190-4440
NG/ML.SOME CASES HAD OTHER
DRUGS DETECTED
LOGAN, B. J. FOR. SCI. (46) 1, 2001
FIVE CASES ONLY ZOLPIDEM
DETECTED (80-1400 NG/ML)
SIGNS OF IMPAIRMENT –SLOW AND
SLURRED SPEECH, SLOW REFLEXES,
DISORIENTATION, LACK OF BALANCE
AND “BLACKING OUT”
SPECIAL CONCERNS
FROM AMBIEN PACKAGE INSERT
SPECIAL CONCERNS
„
„
“SLEEP DRIVING .“ THERE HAVE BEEN
REPORTS OF PEOPLE GETTING OUR OF
BED AFTER TAKING A SLEEP MEDICINE AND
DRIVING THEIR CARS WHILE NOT FULLY
AWAKE, OFTEN WITH NO MEMORY OF THE
EVENT
MEMORY LOSS-AMNESIA
SLEEPWALKING-SOMNANBULISM
SLEEPWALKERS ARE CAPABLE OF
PERFORMING A VARIETY OF ACTIVITIES
FROM SIMPLY GETTING UP AND WALKING
AROUND THE ROOM TO DRIVING A CAR
AND PLAYING AN INSTRUMENT
CHARACTERISTICS OF
SLEEPINGWALKING
„
YOU LEAVE YOUR BED WHILE SLEEPING, USUALLY
IN THE FIRST THIRD OF YOUR SLEEP PATTERN
„
OTHERS FIND IT DIFFICULT TO WAKE YOU DURING
AN EPISODE OF SLEEPWALKING
„
YOU CAN’
CAN’T REMEMBER WHAT HAPPENED WHILE
YOU WERE SLEEPWALKING
CHARACTERISTICS OF
SLEEPINGWALKING
„
WHEN YOU DO WAKE UP FROM AN EPISODE, YOU’
YOU’RE
CONFUSED
„
YOU AREN’
AREN’T SUFFERING FROM DEMENTIA OR ANOTHER
PHYSICAL DISORDER
„
IT IMPAIRS YOUR WORK OR SOCIAL LIFE
SOURCE: DIAGNOSTIC AND STATISTICAL MANUAL OF
MENTAL DISORDERS (DSM(DSM-IV)
Stages of Sleep
AMBIEN CLASS ACTION SUIT
2006
PLAINTIFF JUDITH RENEE LASSWELL
„
LT IN US NAVY WITH 17 YR. SERVICE
„
PRESCRIBED 10 MG AMBIEN IN 2/05 FOR INSOMNIA
„
LASSWELL ALWAYS TOOK IT AT NIGHT AS SHE
WAS GETTING READY TO GO TO BED
„
TAKES AMBIEN AT 7 PM, WENT TO SLEEP AND
ABOUT 9PM ENTERS INTO SOMNAMBULISM
AMBIEN CLASS ACTION SUIT
2006
„
PLAINTIFF DRESSED HERSELF, WALKED TO
INTELLIGENCE CENTER IN A STUMBLING ALMOST
DRIMLEM STATE AMD STARTED TALKING
NONSENSE WITH COCO-WORKERS. THEY WALK HER
BACK TO HER BARACKS, PUT HER BACK INTO BED
AND TOLD HER ABOUT THE INCIDENT THE NEXT
DAY. PLAINTIFF HAD NO MEMORY OF THIS
INCIDENT.
AMBIEN CLASS ACTION SUIT
2006
PLAINTIFF BROTHERS
WORKED AS A FINANCIAL ANALYST WHILE
STUDYING FOR HER CPA
„ PRESCRIBED 10 MG AMBIEN FOR TRANSIENT
INSOMNIA IN MAY OF 2005
„ ON 3RD DAY SHE TOOK THE AMBIEN AROUND 1:57
AM AFTER RETIRING TO BED
„ THE NEXT THING SHE RECALL IS WAKING UP ON
THE CONCRETE FLOOR OF A JAIL CELL
AMBIEN CLASS ACTION SUIT
2006
„
ON SEPT 3, 2006 PLAINTIFF WAS ARRESTED BY
HER BASE POLICE FOR SHOPLIFTING A DVD AND A
CANDLE AT THE BASE EXCHANGE.
„
CHARGES WERE LEVIED UPON PLAINTIFF FOR
OFFOFF-BASE SHOPLIFTING WHERE SHE DROVE TO A
MARSHALLS AND OTHER STORES IN THE AREA.
„
SHE HAS NO RECALL OF THESE EVENTS.
AMBIEN CLASS ACTION SUIT
2006
„
„
„
SHE DISCOVERED LATER FROM THE POLICE
REPORT THAT SHE GOT OUT OF BED AROUND
6AM, LEFT HER HOUSE, DROVE HER MOTHER’
MOTHER’S
CAR INTO A PARKED WEHICLE AND LEFT THAT
SCENE. SHE RANINTO ANOTHER VEHICL, LEFT THE
SCENE AND RETURNED HOME AS IF NOTHING
HAPPENED, HAD A CONVERSATION WITH HER
MOTHER AND WAS ARRESTED IN HER BEDROOM
THAT MORNING
PLAINTIFF HAS NO MEMORY OF THE EVENTS THAT
NIGHT AND INTO THE MORNING LEADING TO HER
ARREST.
PERSONAL CASE REVIEW
„
„
„
„
27 YEAR OLD WHITE FEMALE NURSE WHO
WORKED NIGHT SHIFT
AFTER WORK AT HOME, WATCHED TV(SEVERAL
MOVIES), DRANK BEER (5(5-6 )
TOOK 12.6 AMBIEN CR AROUND 55-6AM AND WENT
TO BED. NOTE. ALSO TOOK A WELLBUTRIN
NEXT THING SHE REMEMBERS IS BEING IN A
POLICE CAR AND TOLD SHE WAS BEING TAKEN
FOR BLOOD DRAW. SHE WAS IN HER NIGHTGOWN
AND WAS BAREFOOK. SHE WAS STOPPED FOR
SWEARING HER VEHCILE ON THE FREEWAY
SO, WHERE ARE WE
FACTORS
„ NOT GOING TO BED RIGHT
AFTER TAKING AMBIEN
„ ATTEMPTING TO DRIVE TO
SOON
„ TAKING TOO MUCH
„INGESTING WITH OTHER
DRUGS
PERSONAL CASE REVIEW
„
„
BLOOD ANALYSIS REPORT NOTED DETECTION OF
BUPROPION METABOLITE AND ZOLPIDEM AT 78
NG/ML. HER BAC WAS 0.19 %
ARRESTING OFFICER STATED HER EYES WERE
HALF OPEN AND SHE HAD A BLANK STARE ON HER
FACE
SO, WHERE ARE WE
HOWEVER
THERE ARE CASES WHERE
PEOPLE GOT OUT OF BED IN
NIGHT CLOTHES, ONLY
AMBIEN DETECTED AND
WERE SLEEPDRIVING
THANK YOU.
ARE THERE ANY QUESTIONS?