Addiction Medicine (ADM)
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Steven C. Boles, D.O., FASAM
Board Certified - FP
ASAM Certified – ADM
Board = American Osteopathic Board of
Family Physicians
ASAM = American Society of Addiction
Medicine
Adjunct Clinical Faculty - Midwestern University
Arizona College of Osteopathic Medicine
Case #1: “Don’t drink
before surgery….”
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45 y/o M, post-op ORIF femur fx
Becomes agitated, slightly febrile
Remains tachycardic, on POD#2
His last drink was 3 DAYS AGO
He was given 4mg lorazepam initially in the ER,
and some BZD’s during surgery 12 hrs later
He is given 80mgs Valium PO that day
But still pulls out his IV, wants to walk, and
Hears noises that aren’t there, per the RN.
Case #1: “Don’t drink
before surgery….”
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The pt at this point
has not had his risk for alcohol
withdrawal syndrome (AWS) recognized
except possibly by the ER.
But that concern, Dx, and Rx
has not been followed-up on
during all the attention
given his surgical problem.
Case #1: “Don’t drink
before surgery….”
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The pt at this point has had
partial Rx for AWS,
blunting its development,
but NOT preventing
the progression into the emergence
of early delirium tremens.
Case #1: “Don’t drink
before surgery….”
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He hears noises that aren’t there, per RN.
He is given IV Haldol 5mgs q 4hrs x 2
And calms down.
He receives Ativan & Haldol
Over the next 48 hrs, in decreasing taper
Goes home POD #5
Case #1: “….., but if you
do, always tell your doctor”
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REMEMBER :
Always give BZD’s BEFORE HALDOL
To avoid SZ’s
And if Haldol is given IV,
Extrapyramidal side effects (EPS’s)
Rarely, if ever, occur.
And what is the top dose of IV Haldol
(haloperidol) that may be given to a
human being???????
Case #1: Alcohol Withdrawal
Syndrome (AWS) & Thiamine
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Give thiamine 100mgs PO/IM/IV
BEFORE ANY GLUCOSE IV
To prevent precipitating :
- Wernicke’s encephalopathy
- Korsakoff’s confabulatory amnestic
psychosis
Case #1: AWS & Thiamine
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Give ALL pts at least 100 mg/day PO.
However,
If alcoholic encephalopathy is present :
- give 200 mg TID, either PO or IV
- for 4 WEEKS
And how would one quickly test for this
type of encephalopathy?
CLINICALLY:
Alcoholic Frontoparietal Hippocampal
Encephalopathy
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Detection : simply add a small test to
the neuro exam
Give them a pen and paper, and ask
them to, “Draw me a clock that says
10 after 11, please.”
Takes 2 minutes or less
You may be VERY surprised at the
response from someone so talkative
Case #1: AWS & Thiamine
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IF EITHER:
Wernicke’s encephalopathy, or
Korsakoff’s amnestic psychosis
are present:
give 1000mg/day of thiamine x 4 wks
(that’s not a misprint)
Case #2: “Lying to your
doctor can be fatal”
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39 y/o F, (+)chronic pain,
Rx’d MTD (methadone) 40 mg/day, X 6 yrs,
presents for detox from BZD’s & cocaine
(family angry w/her)
Wants to stay on her methadone (MTD)
States, “I was in jail for 3 days,
and all they gave me was Risperdal,
and now I’m starting to have WD”.
Case #2: “Lying to your
doctor can be fatal”
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So, pt started on detox for cocaine/BZD
And, she is given her usual
40 mg MTD/day on day #1 of detox (20 mg
BID)
On day #2, pt mildly sedated,
3 hrs post 20mg AM MTD dose.
Total MTD = 60mg thus far
Prior to PM dose, pt is barely arousable
(intoxicated), RR=6/min
Passed out, lying sideways, across her bed.
Case #2: “Lying to your
doctor can be fatal”
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What is the dose of methadone
that can fatal,
if given to an opioid naïve pt?
According to Goodman & Gilman’s
 “The Pharmacological Basis of Therapeutics”,
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(the King James’ version of pharmacology)
it’s only 60mg.
Case #2: “Lying to your
doctor can be fatal”
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Brother verifies she was in jail for 6 wks.
Given 12.5 mg naltrexone PO,
not naloxone (active by IV route).
Pt simply wakes up, has some coffee,
writes a letter (RR=22) and stays up all
night.
Additional 62.5 mg naltrexone given over
next 3 days (MTD obviously DC’d).
Case #2: “Lying to your
doctor can be fatal”
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Acutely precipitation of opioid withdrawal
DID NOT OCCUR, after an opioid
antagonist was given in this case,
As it would have, if her initial HX was true.
And, by the way what did her MTD dosing
curve look like???
After all, she was only given 3 identical
20mg doses.
110
100
90
80
M
70
60
T
50
3 identical 20mg doses of MTD:
- Given 24 hrs apart
- To a pt who is
NOT NEUROADAPTED (i.e. naïve)
to the dose.
Assume 100% absorption & average metabolism
(i.e. pt is not a rapid nor slow metabolizer,
& there are no drug interactions)
40
D
30
20
10
0
12
1
12
2
12
TIME
3
12
hrs
/DAY
4
12
5
12
6
12
7
110
100
90
80
M
70
60
T
INTOXICATED
AND ALMOST
DEAD FROM
VENTILATORY
FAILURE
NALTREXONE 12.5mg given
50
40
D
30
NALTREXONE 25mg given
20
10
0
12
1
12
2
12
TIME
3
12
hrs
/DAY
4
12
5
12
6
12
7
Acute Alcohol Withdrawal
Syndrome (AWS) :
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Signs & Symptoms :
Tachycardia
HT
Diaphoresis
Insomnia
Anxiety
N/V
Acute AWS : symptoms &
signs
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Tremor
Generalized SZ’s
Psychomotor agitation
Hallucinosis/delusions (+/- insight)
DT’s
AWS : Hallucinosis
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Visual :
- lights too bright
- animal life: dogs, rodents, bugs in room
AWS : Hallucinosis
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Auditory :
- sounds too loud/startling
- start out as unformed sounds
clicking
buzzing
thumping from other room
- may progress to formed voices
AWS : Hallucinosis
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Auditory :
Formed voices
- friends/relatives
- accusatory in nature
In contrast to those of schizophrenia :
- religious
- political
AWS : Delusions
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“I need to get dressed.”
“I need go to work.”
“I’ve got bills to pay.”
“I gotta get outa here.”
Acute AWS begins when Etoh
levels start to fall, if the pt is
neuroadapted to ETOH
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Driven by :
Downregulation of inhibitory systems
Upregulation of excitatory systems
Dysregulating LC :
NE output
Resultant hypernoradrenergic activity
From the brainstem.
AWS : withdrawal
seizures (WD SZ’s)
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Begin: 8 – 24 hrs AFTER LAST DRINK
May occur BEFORE a pt’s BAL=0
Peak: 24 hrs after last drink
Type: grand mal (generalized)
singly, or in bursts
over a period of 1 – 6 hrs
Dilantin (phenytoin) is not effective Rx.
AWS : WD SZ’s
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Risk of occurrence in pt’s with :
genetic predisposition
(+)Hx of prior WD SZ’s (“kindling”)
undergoing concurrent WD from :
- BZD’s
- BARB’s
- nonBARB sedatives (Soma / GHB)
DT’s
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Generally appear 72 – 96 hrs
After last drink
That’s 3 – 4 DAYS AFTER LAST DRINK
lasting for an
ADDITIONAL 2 – 3 DAYS (rare > 50 d)
If someone starts into AWS + DT’s,
You’re looking at ONE WEEK.
CLASSIC DT’s
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(+) all S&S’s of mild AWS, only now
SEVERE :
- tachycardia
- HT
- diaphoresis
- tremor
- fever
CLASSIC DT’s
(cont.d)
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- global confusion
- absorbed in a separate psychic reality
- believes him/her self to be in a
location other than hospital
- may misidentify staff as
personal acquaintances
- hallucinations without insight
CLASSIC DT’s
(cont.d)
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- marked psychomotor agitation
- efforts to get out of bed
LASTING FOR HOURS
- absence of clear sleep
LASTING FOR DAYS
Always monitor & Rx these pt’s
IN AN ICU
RISK OF DT’s :
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(+) BAL > 300 mg/dl at presentation
(+) AWS seizure (SZ) at presentation
AWS Rx :
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KEY : EARLY RX with BZD’s
To PREVENT potentially FATAL DT’s
To shorten Rx time
Increase pt safety & comfort
Prevent intercurrent medical complications
BZD of choice :
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Use : DIAZEPAM (Valium), PO/IV
NEVER : IM
- variable absorbtion with
- slow/undependable onset
- delayed respiratory depression
If IM BZD needed : LORAZEPAM (Ativan)
(Lorazepam may also be given IV)
Exception to Valium Rx :
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Two groups of pts :
#1 = Elderly
#2 = Significant liver disease
- (GGT > 600)
- underlying active viral hepatits (HCV)
- hepatic cirrhosis
Exception to Valium Rx :
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BOTH groups of pts have
reduced BZD elimination, but
CYP oxidative pathways
are reduced FAR MORE, than
the glucuronide conjugation pathways.
Exception to Valium Rx :
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In these pts, use
Lorazepam (Ativan)
Oxazepam (Serax)
Because both drugs are
ALREADY 3-OH BZD’s
and therefore
Exception to Valium Rx :
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only require glucuronidation
for elimination; and this avoids
ACCUMULATION of toxic/sedating
prodrug, or
intermediate active metabolites,
resulting from 2-keto BZD metabolism
(Valium/Librium are 2-keto BZD’s)
2-KETO BZD’s
N-DESALKYLATED
COMPOUNDS
3-OH BZD’s
CHLORDIAZEPOXIDE
(LIBRIUM) (Intermediate)
DEMOXEPAM
(Long)
TEMAZEPAM
(RESTORIL) (Int)
DIAZEPAM
(VALIUM) (Long)
NORDIAZEPAM
(Long)
OXAZEPAM
(SERAX) (Int)
TRIAZOLO BZD’s
TRIAZOLAM
(HALCION) (Short)
ALPRAZOLAM
(XANAX) (Short)
LORAZEPAM
(ATIVAN) (Int)
ALPHA –OH’s
via oxidation
(Short)
7-NITRO BZD’s
CLONAZEPAM
(KLONOPIN) (Long)
Nitroreduction
& acetylation
(NO ACTIVE METABOLITE)
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REMEMBER :
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All BZD’s reduce AWS symptoms, but
Diazepam, lorazepam, and clonazepam
Are better ANTICONVULSANTS
(because they have larger volumes of
distribution, and are more lipophilic)
than either
chlordiazepoxide (Librium), or
oxazepam (Serax)
REMEMBER :
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ALWAYS give Valium/Ativan
BEFORE the Haldol,
to eliminate/reduce risk of SZ’s from
haloperidol
AWS Rx : Structured BZD
Dosing on med/surg floor
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DIAZEPAM :
- 20mg PO q 6 hrs x 4 doses, then
- 10mg PO q 6 hrs x 4 doses, then
- 5mg PO q 6 hrs x 4 doses, then DC
Closely monitor pt
Give additional doses, or hold doses,
prn
AWS Rx : Structured BZD
Dosing on med/surg floor
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LORAZEPAM :
- 2mg PO or IV q 6 hrs x 4 doses, then
- 1mg PO or IV q 6 hrs x 4 doses, then
- 0.5mg PO or IV q 6 hrs x 4 doses, then
DC
Same precautions
AWS Rx : Symptom- Triggered BZD Protocol
on a Chemical Dependency (CD) Unit
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VALIUM :
5-20 mg PO q 1-2 hrs, prn CIWA-r scale
Usually results in :
- 140mg Day #1
- 70mg Day #2
- 30mg Day #3
None, or 5mg last day
AWS Rx : Symptom- Triggered BZD
Protocol on a Chemical Dependency (CD)
Unit
AWS Rx : SymptomTriggered BZD Protocol
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If agitation :
- Ativan 2-4mg PO/IM q 6 hrs
If psychotic symptoms :
- Ativan 2-4mg PO/IM q 6 hrs, then
- Haldol 2-5mg PO/IM q 6 hrs with
- Benadryl 50mg PO/IM q 6 hrs
If more than 1 dose Haldol given, then begin
- Cogentin 1mg PO q 12 hrs
AWS Rx : DT’s
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**
Ativan 1mg IV + Haldol 2mg IV, then
Ativan 2mg IV + Haldol 3mg IV, then
Ativan 3mg IV + Haldol 5mg IV
Q 20 MIN, going up scale,
IF NO RESPONSE to prior dose.
May repeat scale q 2-3 hrs, prn
Pt must be monitored in ICU
AWS Rx : DT’s
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If not controlled with above, then
Paralyze
Completely sedate
Intubate & ventilate
Provide supportive ICU care
Hope pt does not die
Etoh Pharmacology :
Elimination
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Elimination Rate = 20 mg/dl, per hr,
in the serum, based on the BAL lab test.
The absolute amount of alcohol
eliminated
from the body is 10 grams per hour,
or about the amount of alcohol in a
“standard drink”
Etoh Pharmacology :
Elimination
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(BAL) + (20)(hrs since last drink)
=
Calculated BAL @ time of the last drink
Used to predict the SEVERITY of :
- impending AWS
- risk of DT’s, or SZ’s
during AWS.
Is the Breathalyzer in
agreement with BAL ?
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Breathalyzer result of 0.100 means:
= 0.100 grams Etoh / 210 L of expired
deep lung air
= (0.476 mg / L) = (0.05% of the BAL)
BAL = 950 mg / L
BAL = 95 mg / dl
BAL ~ 100 mg/dl, i.e., legally drunk
Case #3: What’s the Dx?
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In the mid 1980’s,
The supertanker, “Exxon Valdez”
ran aground in Alaska.
Captain Hazelwood’s BAL was
reported to be = 61 mg/dl
(Breathalyzer = 0.061)
Case #3: What’s the Dx?
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But it was drawn
11 hrs AFTER the grounding.
Retrograde extrapolation,
determined his BAL = 226mg/dl,
(Breathalyzer = 0.226)
at the time of the accident,
by Dr. David Smith,
during his trial testimony.
Case #3: What’s the Dx?
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I would have calculated it as :
(11 hrs) x (20 mg/dl per hr) + ( 61 mg/dl )
= 281 mg/dl BAL,
( Breathalyzer = 0.281 ),
AT THE TIME OF THE OF THE ACCIDENT,
At the time of his last drink.
But they didn’t call me.
Case #3: What’s the Dx?
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Either way, he was really drunk.
But the ever vigilant Coast Guard
Never detected any signs of insobriety
Other than the smell of alcohol.
Case #3: What’s the Dx?
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ANYONE who can
operate a supertanker,
with a BAL = 281 mg/dl,
and not APPEAR DRUNK
Case #3: What’s the Dx?
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to the cop who arrested him,
is neuroadapted to Etoh;
and, therefore his Dx is
ALCOHOLISM.
And he is also at a very high risk
for alcohol withdrawal seizures
& subsequent DT’s.
HALFTIME BREAK
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ACUTE WDS
HIGH DOSE, ANY
LOW DOSE
SHORT ACTING
LOW DOSE
LONG ACTING
PROLONGED
POST ACUTE
WDS (PAWS)
2 4 6 8 10 12 14 16 18 20 22 24 26 28
DAYS
2 4 6 8 10 12
MONTHS
DURATION OF SEDATIVE – HYPNOTIC / BZD WDS
Case #4: Subpoenaed
to provide testimony
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47 y/o M crashes into parked cars in his
neighborhood one afternoon
An 8-page report is generated by the
arresting officer & DRE on the scene
DRE = Drug Recognition Expert
The report details the driver’s (your pt’s)
condition at the time :
Case #4: Subpoenaed
to provide testimony
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-
dilated pupils, bloodshot eyes
persistently elevated BP & pulse
diaphoresis
shaking, twitching, tremor
rapid speech,
at times not making sense
high anxiety level
Case #4: Subpoenaed
to provide testimony
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He is arrested for driving impaired,
Under the influence OF A STIMULANT
subsequent UDS/serum drug screen:
- acetylsalicylic acid
- cotinine
- caffeine
- nordiazepam
Case #4: Subpoenaed
to provide testimony
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You prescribed
Librium (chlordiazepoxide)
2 months previously, to help him
stop drinking after he was released
from jail for a DUI.
His defense attorney would like you to
explain ANY of this at trial, if you can.
Case #4: At trial, on the
witness stand
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You look at the forensic lab tech, and
note her fine & accurate work.
You tell the judge & jury that the drugs
represent :
Cigarettes (cotinine metabolite);
Aspirin (acetylsalicylic acid);
Coffee (caffeine); and
Librium (nordiazepam metabolite).
Case #4: On the stand
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You explain to them that nordiazepam is
psychoactive by-product of Librium
and that both are sedatives/tranquilizers.
You look at the DRE, and commend him
on his very accurate & detailed 8 page
report (with small, neat, block-printing).
He proudly returns your gaze.
Case #4: On the stand
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You also agree, in your expert opinion,
that the pt was indeed
under the influence of a stimulant, at the
time of the accident.
But, that the stimulant was the natural
norepinephrine IN HIS BRAIN,
and not any illicit substance,
since none was detected
upon forensic testing.
Case #4: On the stand
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You look at the at everyone in the
courtroom, and explain the
ONLY POSSIBLE EXPLANATION FOR
THESE FACTS
are that the alcoholic defendant
was in early DT’s from AWS,
and even though this is very dangerous,
it is not against the law.
Case #4: On the stand
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You look back to the DRE, and he
looks down at all his hard work,
and almost starts to cry.
You also explain that the pt was clearly
not under the influence of a
tranquilizer, and in fact, if he had taken
MORE Librium, he wouldn’t have had
the accident in the first place.
Case #4: On the stand
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You further comment that the T1/2 of
Librium = 100 hrs (4 days)
Nordiazepam = 200 hrs (8 days)
especially in someone with early cirrhosis.
And that it takes ~ 10-12 T1/2’s
to clear any drug from the body,
explaining the (+) UDS, 60 days later.
Case #4: On the stand
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Also note:
There was NO PARENT COMPOUND
found on the UDS
There was no chlordiazepoxide
Only its metabolite, nordiazepam
Indicating this WAS NOT an acute
intoxication reaction from the Librium
2-KETO BZD’s
N-DESALKYLATED
COMPOUNDS
3-OH BZD’s
CHLORDIAZEPOXIDE
(LIBRIUM) (Intermediate)
DEMOXEPAM
(Long)
TEMAZEPAM
(RESTORIL) (Int)
DIAZEPAM
(VALIUM) (Long)
NORDIAZEPAM
(Long)
OXAZEPAM
(SERAX) (Int)
TRIAZOLO BZD’s
TRIAZOLAM
(HALCION) (Short)
ALPRAZOLAM
(XANAX) (Short)
LORAZEPAM
(ATIVAN) (Int)
ALPHA –OH’s
via oxidation
(Short)
7-NITRO BZD’s
CLONAZEPAM
(KLONOPIN) (Long)
Nitroreduction
& acetylation
(NO ACTIVE METABOLITE)
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ACUTE WDS
HIGH DOSE, ANY
LOW DOSE
SHORT ACTING
LOW DOSE
LONG ACTING
PROLONGED
POST ACUTE
WDS (PAWS)
2 4 6 8 10 12 14 16 18 20 22 24 26 28
DAYS
2 4 6 8 10 12
MONTHS
DURATION OF SEDATIVE – HYPNOTIC / BZD WDS
Mild-Moderate BZD WDS :
Adrenergic / Autonomic
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Anxiety
Restlessness / agitation
N/V, yawning
Insomnia
HT
Tachycardia
Mydriasis (dilated pupils)
Severe BZD WDS :
Adrenergic /Autonomic
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Autonomic hyperactivity
Unstable vital signs
Hyperpyrexia (fever)
BZD WDS :
Musculoskeletal
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Tremor
Weakness
Fasciculations
Spasms
Cramps
Hyperreflexia
BZD WDS : Mild-Moderate
Neuropsychiatric
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Sensory
Hypersensitivity to
- light, sound, touch, smell
Light headedness / dizziness
Depression
Depersonalization
Confusion
Difficulty expressing thoughts
BZD WDS : Severe
Neuropsychiatric S&S’s
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Psychosis
Delusions
Hallucinations
Mania
Catatonia
Delirium
SZ’s
BZD WDS : Sort of sounds
like AWS, doesn’t it?
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Both Etoh & BZD’s
Are GABA-receptor agonists
Whose WDS’s are really unopposed
Down-regulated GABA withdrawal
syndrome (WDS)
Sedative-Hypnotic WDS :
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Will occur after prolonged, high-dose
exposure, & neuroadaptation, to any of
the following:
Non-BARB / Non-BZD meds : e.g.
- Chloral hydrate (Noctec)
- Meprobamate (Equanil, Miltown)
- Carisopradol (Soma)
Or
any similarly dosed BARBITURATE
Sedative-Hypnotic WDS :
Severe Neuropsychiatric S&S’s
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Delirium
Psychosis
Hallucinations
Hyperthermia
Cardiac arrest & death
Sedative-Hypnotic WDS :
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Is essentially IDENTICAL to AWS
(Alcohol Withdrawal Syndrome)
Because BOTH
Etoh & BARB’s pharmacologically are
GABA receptor agonists &
NMDA-Glutamate receptor antagonists
Sedative-Hypnotic WDS :
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Is essentially IDENTICAL to AWS
Because after neuroadaptation,
Both syndromes represent the newly
unopposed pathologic effect of
Down-regulated GABA receptors
Combined with
Up-regulated NMDA-Glu receptors
BZD WDS will exacerbate
these comorbid conditions :
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CAD / cardiac dysrhythmias / CV disease
Asthma
SLE
Inflammatory bowel disease
Severe NIDDM/IDDM
Severe arthritis
Severe thyroid disease
BZD & Sedative-Hypnotic
WDS Rx : INPT use ONLY
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Phenobarb substitution method :
- compute PB equivalent dose/day
- note: this is NOT same as therapeutic
dose equivalency,
- but it will prevent severe WDS
BZD & Sedative-Hypnotic
WDS Rx :
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-
DRUG : PHENOBARBITAL EQUIVALENT
Xanax 1mg : PB 30mg
Klonopin 2mg : PB 30mg
Valium 10mg : PB 30mg
Fiorinal 2 tabs : PB 30mg
Soma 2 tabs : PB 30mg
Ativan 2mg : PB 30mg
BZD & Sedative-Hypnotic
WDS Rx :
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The MAXIMUM STARTING DOSE of PB
Is 500mg/day
The computed PB equivalent
Is given in divided doses TID / QID
And reduced by about 30mg per day,
With dose titration up, or down, PRN
BZD & Sedative-Hypnotic
WDS Rx :
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A pt taking
Xanax 6mg/day, plus
Soma 8/day, plus
6 pack of beer/day
Gets : 6 + 4 + 3 = 13 PBE’s
= 13 x 30mg PB
= 390mg PB day #1
BZD & Sedative-Hypnotic
WDS Rx :
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Phenobarb 120mg x 1, then
1
90mg q 6hr x 3 doses, then
75mg q 6hr x 4 doses, then
60mg q 6hr x 4 doses, then
60mg q 8hr x 3 doses, then
45mg q 8hr x 3 doses, then
30mg q 8hr x 3 doses, then
15mg q 12hr x 2 doses, then DC
st
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24 hrs=390mg
BZD & Sedative-Hypnotic
WDS Rx :
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Observe pt for any of the 3 signs of
toxicity before each dose of PB :
- nystagmus
- ataxia
- dysarthria
If any 1 present, skip 1 dose
If any 2 present, skip 2 doses
Case #5: Consult in ICU
“The confused pt”
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They want to know if there are any
drug WDS
that produce obtundation, or coma,
on the 3rd-4th day
after doing well the first 2 days?
42 y/o M, came in agitated, paranoid,
hallucinating.
(+) known “heavy drinker/IVDU”
UDS = (+) AMPHET only
Case #5: Consult in ICU
“The confused pt”
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BAL = 0
(+) elevated vital signs
(+) ALT= 112, AST= 84, GGT=213
Alb=3.4, Bili=2.1 (other labs WNL)
“We followed the CD protocol, to prevent
suspected AWS & DT’s.
Now it’s the 4th day he’s been in ICU; his
vitals are OK, but we can’t wake him up.”
Case #5: Consult in ICU
“The confused pt”
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“Really.
“Exactly what did you give him?”
“He had 4mg Ativan & 3mg Haldol in ER.
We gave him, let’s see, a total of 70mg
Valium over the first 36 hrs.”
“I see. Well, it does look like you followed
the protocol, ……sort of.
You just forgot one very important thing.”
Case #5: Consult in ICU
“The confused staff”
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There are no WDS’s that progress to
coma/obtundation
(severe BZD WDS may include catatonia,
but not coma)
Pt had: Stimulant Intoxication Psychosis,
evidenced by UDS (+) for AMPHETAMINE
WHEN HAVING PSYCHOTIC SYMPTOMS .
Additionally,
Case #5: the ICU pt &
“The confused staff”
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He ALSO was at risk for, or
simultaneously in, DT’s.
(a very bad combination).
He had hepatic insufficiency, per labs,
with ALD (alcoholic liver disease),
superimposed on
chronic active HCV hepatitis.
(another VERY bad combination).
Case #5: the ICU pt
(the problem with the case)
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Suspected by ALT > AST (confirmed later
by additional Hx, & (+) HCV Ab)
The problem was not recognizing the
severity of his liver disease / oxidative
deficiency,
compounded by giving him a 2-keto BZD
(Valium),
instead of a 3-OH BZD
(Ativan / Serax).
Case #5: the ICU pt
(the problem with the case)
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Leading to accumulation of :
- unmetabolized diazepam, and it’s active
metabolite,
- desmethyldiazepam (nordiazepam).
Both of which have T1/2’s of about 100 hrs
(4 days),
and both are psychoactive CNS depressants.
I told them to DC the Valium,
and he’d wake up in 2 weeks.
2-KETO BZD’s
N-DESALKYLATED
COMPOUNDS
3-OH BZD’s
CHLORDIAZEPOXIDE
(LIBRIUM) (Intermediate)
DEMOXEPAM
(Long)
TEMAZEPAM
(RESTORIL) (Int)
DIAZEPAM
(VALIUM) (Long)
NORDIAZEPAM
(Long)
OXAZEPAM
(SERAX) (Int)
TRIAZOLO BZD’s
TRIAZOLAM
(HALCION) (Short)
ALPRAZOLAM
(XANAX) (Short)
LORAZEPAM
(ATIVAN) (Int)
ALPHA –OH’s
via oxidation
(Short)
7-NITRO BZD’s
CLONAZEPAM
(KLONOPIN) (Long)
Nitroreduction
& acetylation
(NO ACTIVE METABOLITE)
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Cocaine :
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Pharmacokinetics :
T1/2 cocaine = 40-60 min
Metabolized by
- plasma cholinesterase to
- benzoylecgonine, found in urine
- up to 48 hrs, on UDS
Cocaine Intoxication :
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Psychiatric effects :
(+) mimics naturally occurring mania
Cocaine induced paranoia is usually
distinguished by drug content on UDS
May precipitate, or exacerbate
- major psychiatric Dx’s
Cocaine Intoxication :
Medical aspects
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Cardioventricular tachydysrythmias
Acute MI / Aortic dissection
Vasospasm, thrombosis, ischemia,
necrosis (any organ, e.g. retinal artery)
Asthma / pulmonary dysfunction with
melanoptysis (“crack lung”)
Pneumomediastinum / pneumothorax
Intrauterine / placenta abruptio
Cocaine Intoxication :
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Psychiatric effects :
(+) mimics naturally occurring mania
Cocaine induced paranoia is usually
distinguished by drug content on UDS
May precipitate, or exacerbate
Almost any major psychiatric Diagnosis
Amphetamine &
Methamphetamine (MA) :
Intoxication
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Repeated administration may cause :
- paranoid psychosis
- stereotypical behaviors with repeated
touching / picking / bruxism
during the intoxication phase,
but not the withdrawal phase.
Amphetamines / MA
Intoxication :
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Medical effects :
- HT, tachydysrythmias
- hyperthermia
- SZ’s
- malnutrition
- cerebral vasculitis
- orofacial dyskinesias
(remember the “binky” with MDMA)
Psychomotor Stimulant
Intoxication : (+) Aminergic
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Restlessness, irritability, tremor
Talkativeness
Anxiety
Labile mood (esp. violence with MA)
HA
Chills, vomiting, diaphoresis
Delirium
Psychomotor Stimulant
Intoxication : Psychiatric
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- Hypervigilance
- Panic reactions
- Compulsive stereotypical behavior
- Paranoia
All of which is often referred to as,
“Tweaking”
Psychomotor Stimulant
Intoxication : Rx
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(+) Agitation / anxiety :
- Ativan 1-2 mg IV/IM/PO q 30-60 min
- Valium 10-30 mg PO q 30-60 min
Psychomotor Stimulant
Intoxication Psychosis Rx :
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Ativan 1mg IV + Haldol 2mg IV, then
Ativan 2mg IV + Haldol 3mg IV, then
Ativan 3mg IV + Haldol 5mg IV
Q 20 MIN, going up scale,
if no response to prior dose.
May repeat scale q 2-3 hrs, prn
Pt must be monitored in ICU
(Just like treating DT’s, isn’t it?)
Cocaine, MA, or other
stimulant WDS :
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(+)
(+)
(+)
(+)
(+)
(+)
“craving”
depressed mood
anhedonia
pleasure deficiency syndrome
fatigue
hypersomnolence
Cocaine, MA, or other
stimulant WDS (cont.d) :
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THERE IS NO SPECIFIC DRUG Rx
REQUIRED,
BUT IF PSYCHOTIC SYMPTOMS PERSIST
BEYOND 4 DAYS,
THEN ANTIDEPRESANTS OR
ANTIPSYCHOTICS
MAY BE INDICATED
OWS “The flu” : Serotonergic/
Adrenergic signs & symptoms
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Myalgias & arthralgias
Dysphoria / Depressed mood
ANXIETY
Perspiration / diaphoresis
Fever
Exacerbation of ANY comorbid painful
medical or orthopedic condition
OWS “The flu” : Cholinergic
signs & symptoms
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Lacrimation
Rhinorrhea
Yawning
N/V
Diarrhea / intestinal CRAMPS
OWS “The flu” : Dopaminergic
signs & symptoms
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Anhedonia
Opioid craving
Opioid seeking behavior
Case #6: “The DEA”
(Don’t Ever Attempt)
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27 y/o F, (+)ODS, presents to the office,
Desiring detox from smoking heroin.
Percocet & Ativan are prescribed for detox,
and she is told to continue attending AA.
Anything wrong with this treatment?
2 weeks later, she presents for inpt detox
What went wrong?
Case #6:
ADM point of view:
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Never give prn mood altering meds to
an addict, and expect him/her
to control them.
After all, their disease is characterized by
LOSS OF CONTROL OVER USE.
The treatment can, therefore,
be reasonably expected to fail.
Case #6: Administering or
Dispensing Narcotic Drugs
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21 CFR (1306.07) :
To AMINISTER, or DISPENSE
(BUT NOT PRESCRIBE),
narcotic drugs to a narcotic dependent person
for “detoxification treatment”, or “maintenance
treatment”, a physician
MUST HAVE A SEPARATE REGISTRATION
with the attorney general.
[Sec. 303 (g) of the Act (21 U.S.C. 823 (g)]
Case #6:
DEA point of view:
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Traditionally, treating addiction to opiates
with opioids (methadone)
without a separate DEA registration
as a Narcotic Treatment Program,
(that means being a methadone clinic)
Case #6:
DEA point of view:
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Or without having a waiver from SAMHSA
to prescribe buprenorphine
(Suboxone or Subutex)
is not included in the CSA,
and therefore, such activity is
OUTSIDE
THE SCOPE OF MEDICAL PRACTICE,
AND THEREFORE, IS ILLEGAL.
Case #7: “What shall I
name my new hospital?”
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A 29 y/o pt (+)ODS,
In methadone (MTD) clinic,
presents on a weekend, to ER,
claiming her MTD take-home dose
is lost, stolen, wasn’t picked up, etc…..
The pt has no other medical problems.
“I’m afraid of having MTD withdrawal.”
Case #7: “What shall I
name my new hospital?”
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(+) anxiety, elevated vitals are noted.
The pt was given Ativan & clonidine,
and then DC’d to home by POV.
Was this a good idea?
No.
The pt promptly took all of their meds
at one time; and then promptly,
“Fell asleep at the wheel”,
and rolled their vehicle several times.
Case #7: What else could
have been done?
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First off, the ER should DOCUMENT THAT
THE PT WAS IN OWS, IF ANY FORM OF
TREATMENT WAS TO BE OFFERED.
Absent signs & symptoms of OWS,
NO Dx could have been made, other than
ODS, and NO Rx would be indicated.
Additionally, in this pt’s case,
a UDS should confirm the presence of
MTD, if MTD was taken within 2-3 days.
Case #7: What else could
have been done?
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Note: the UDS employed must be able to
detect MTD,
as MTD does NOT GIVE A (+) RESULT AS
AN “OPIATE” ON A SCREENING TEST.
MTD is reported as “MTD”.
Remember MTD is structurally different
from MS/codeine (opiates), and other
synthetic opioids.
Remember the signs & symptoms of OWS
Case #7: What else could
have been done?
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ADMINISTER 15mg MTD PO / IM x 1 dose
Observe for relief of OWS at 3 hrs post dose,
and document findings.
Arrange for referral to treatment center.
Instruct pt to return the following day
To determine if another MTD dose should be
administered (but not prescribed).
DO NOT PRESCRIBE OR DISPENSE ANY
OPIODS
Under what authority can this be done?
Case #7: Controlled
Substances Act
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Same law: 21 CFR 1306.07 (b)
“Nothing in this section of the law shall prohibit
a practitioner who is not specifically registered
to conduct a NTP
From ADMINISTERING
(BUT NOT PRESCRIBING) narcotic drugs
To a narcotic dependant person
for the purposes of relieving
acute withdrawal symptoms when necessary
Case #7: 21 CFR 1306.07 (b)
(cont’d.)
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while arrangements are being made
for referral for treatment.
Not more than one day’s medication
may be ADMINISTERED
to the person AT ONE TIME.
Such emergency treatment may be carried out
for NOT MORE THAN 3 DAYS,
and MAY NOT BE RENEWED or extended”.
And in closing,
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I’m pleased we could spend this time
together today.
Good luck on your Boards.
I’m grateful you were so attentive.
Thank you.