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Addiction Medicine (ADM). 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

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addiction medicine adm
Addiction Medicine (ADM)
  • 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
Case #1: “Don’t drink before surgery….”
  • 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 surgery1
Case #1: “Don’t drink before surgery….”
  • 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 surgery2
Case #1: “Don’t drink before surgery….”
  • 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 surgery3
Case #1: “Don’t drink before surgery….”
  • 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
Case #1: “….., but if you do, always tell your doctor”
  • 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
Case #1: Alcohol Withdrawal Syndrome (AWS) & Thiamine
  • 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
Case #1: AWS & Thiamine
  • 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
CLINICALLY:Alcoholic Frontoparietal Hippocampal Encephalopathy
  • 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 thiamine1
Case #1: AWS & Thiamine
  • 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
Case #2: “Lying to your doctor can be fatal”
  • 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 fatal1
Case #2: “Lying to your doctor can be fatal”
  • 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 fatal2
Case #2: “Lying to your doctor can be fatal”
  • 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”,
  • (the King James’ version of pharmacology)
  • it’s only 60mg.
case 2 lying to your doctor can be fatal3
Case #2: “Lying to your doctor can be fatal”
  • 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 fatal4
Case #2: “Lying to your doctor can be fatal”
  • 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.
slide16

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)

110

100

90

80

M

T

D

70

60

50

40

30

20

10

0

12 1 12 2 12 3 12 4 12 5 12 6 12 7

TIMEhrs/DAY

slide17

110

INTOXICATED AND ALMOST DEAD FROM VENTILATORY FAILURE

100

90

80

M

T

D

70

60

NALTREXONE 12.5mg given

50

40

30

NALTREXONE 25mg given

20

10

0

12 1 12 2 12 3 12 4 12 5 12 6 12 7

TIMEhrs/DAY

acute alcohol withdrawal syndrome aws
Acute Alcohol Withdrawal Syndrome (AWS) :
  • Signs & Symptoms :
  • Tachycardia
  • HT
  • Diaphoresis
  • Insomnia
  • Anxiety
  • N/V
acute aws symptoms signs
Acute AWS : symptoms & signs
  • Tremor
  • Generalized SZ’s
  • Psychomotor agitation
  • Hallucinosis/delusions (+/- insight)
  • DT’s
aws hallucinosis
AWS : Hallucinosis
  • Visual :
  • - lights too bright
  • - animal life: dogs, rodents, bugs in room
aws hallucinosis1
AWS : Hallucinosis
  • Auditory :
  • - sounds too loud/startling
  • - start out as unformed sounds
  • clicking
  • buzzing
  • thumping from other room
  • - may progress to formed voices
aws hallucinosis2
AWS : Hallucinosis
  • Auditory :
  • Formed voices
  • - friends/relatives
  • - accusatory in nature
  • In contrast to those of schizophrenia :
  • - religious
  • - political
aws delusions
AWS : Delusions
  • “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
Acute AWS begins when Etoh levels start to fall, if the pt is neuroadapted to ETOH
  • 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
AWS : withdrawal seizures (WD SZ’s)
  • 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
AWS : WD SZ’s
  • 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)
slide27
DT’s
  • 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
CLASSIC DT’s
  • (+) all S&S’s of mild AWS, only now
  • SEVERE :
  • - tachycardia
  • - HT
  • - diaphoresis
  • - tremor
  • - fever
classic dt s cont d
CLASSIC DT’s(cont.d)
  • - 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 d1
CLASSIC DT’s(cont.d)
  • - 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
RISK OF DT’s :
  • (+) BAL > 300 mg/dl at presentation
  • (+) AWS seizure (SZ) at presentation
aws rx
AWS Rx :
  • KEY : EARLY RX with BZD’s
  • To PREVENT potentially FATALDT’s
  • To shorten Rx time
  • Increase pt safety & comfort
  • Prevent intercurrent medical complications
bzd of choice
BZD of choice :
  • 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
Exception to Valium Rx :
  • Two groups of pts :
  • #1 = Elderly
  • #2 = Significant liver disease
  • - (GGT > 600)
  • - underlying active viral hepatits (HCV)
  • - hepatic cirrhosis
exception to valium rx1
Exception to Valium Rx :
  • BOTH groups of pts have
  • reduced BZD elimination, but
  • CYP oxidative pathways
  • are reduced FAR MORE, than
  • the glucuronide conjugation pathways.
exception to valium rx2
Exception to Valium Rx :
  • In these pts, use
  • Lorazepam (Ativan)
  • Oxazepam (Serax)
  • Because both drugs are
  • ALREADY 3-OH BZD’s
  • and therefore
exception to valium rx3
Exception to Valium Rx :
  • 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)
slide38

2-KETO BZD’s

N-DESALKYLATED

COMPOUNDS

3-OH BZD’s

DEMOXEPAM

(Long)

TEMAZEPAM

(RESTORIL) (Int)

G

L

U

C

U

R

O

N

I

D

A

T

I

O

N

CHLORDIAZEPOXIDE

(LIBRIUM) (Intermediate)

DIAZEPAM

(VALIUM) (Long)

NORDIAZEPAM

(Long)

OXAZEPAM

(SERAX) (Int)

TRIAZOLO BZD’s

LORAZEPAM

(ATIVAN) (Int)

TRIAZOLAM

(HALCION) (Short)

ALPRAZOLAM

(XANAX) (Short)

ALPHA –OH’s

via oxidation

(Short)

7-NITRO BZD’s

Nitroreduction

& acetylation

(NO ACTIVE METABOLITE)

CLONAZEPAM

(KLONOPIN) (Long)

remember
REMEMBER :
  • 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)
remember1
REMEMBER :
  • 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
AWS Rx : Structured BZDDosing on med/surg floor
  • 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 floor1
AWS Rx : Structured BZDDosing on med/surg floor
  • 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
AWS Rx : Symptom- Triggered BZD Protocol on a Chemical Dependency (CD) Unit
  • 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
AWS Rx : Symptom- Triggered BZD Protocol
  • 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
AWS Rx : DT’s**
  • 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 s1
AWS Rx : DT’s
  • If not controlled with above, then
  • Paralyze
  • Completely sedate
  • Intubate & ventilate
  • Provide supportive ICU care
  • Hope pt does not die
etoh pharmacology elimination
Etoh Pharmacology :Elimination
  • 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 elimination1
Etoh Pharmacology :Elimination
  • (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
Is the Breathalyzer in agreement with BAL ?
  • 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
Case #3: What’s the Dx?
  • 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 dx1
Case #3: What’s the Dx?
  • 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 dx2
Case #3: What’s the Dx?
  • 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 dx3
Case #3: What’s the Dx?
  • 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 dx4
Case #3: What’s the Dx?
  • ANYONE who can
  • operate a supertanker,
  • with a BAL = 281 mg/dl,
  • and not APPEAR DRUNK
case 3 what s the dx5
Case #3: What’s the Dx?
  • 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.
slide59

W

I

T

H

D

R

A

W

A

L

I

N

T

E

N

S

I

T

Y

HIGH DOSE, ANY

ACUTE WDS

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 2 4 6 8 10 12

DAYS MONTHS

DURATION OF SEDATIVE – HYPNOTIC / BZD WDS

case 4 subpoenaed to provide testimony
Case #4: Subpoenaedto provide testimony
  • 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 testimony1
Case #4: Subpoenaedto provide testimony
  • - 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 testimony2
Case #4: Subpoenaedto provide testimony
  • 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 testimony3
Case #4: Subpoenaedto provide testimony
  • 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
Case #4: At trial, on the witness stand
  • 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
Case #4: On the stand
  • 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 stand1
Case #4: On the stand
  • 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 stand2
Case #4: On the stand
  • 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 stand3
Case #4: On the stand
  • 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 stand4
Case #4:On the stand
  • 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 stand5
Case #4:On the stand
  • 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
slide71

2-KETO BZD’s

N-DESALKYLATED

COMPOUNDS

3-OH BZD’s

DEMOXEPAM

(Long)

TEMAZEPAM

(RESTORIL) (Int)

G

L

U

C

U

R

O

N

I

D

A

T

I

O

N

CHLORDIAZEPOXIDE

(LIBRIUM) (Intermediate)

DIAZEPAM

(VALIUM) (Long)

NORDIAZEPAM

(Long)

OXAZEPAM

(SERAX) (Int)

TRIAZOLO BZD’s

LORAZEPAM

(ATIVAN) (Int)

TRIAZOLAM

(HALCION) (Short)

ALPRAZOLAM

(XANAX) (Short)

ALPHA –OH’s

via oxidation

(Short)

7-NITRO BZD’s

Nitroreduction

& acetylation

(NO ACTIVE METABOLITE)

CLONAZEPAM

(KLONOPIN) (Long)

slide72

W

I

T

H

D

R

A

W

A

L

I

N

T

E

N

S

I

T

Y

HIGH DOSE, ANY

ACUTE WDS

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 2 4 6 8 10 12

DAYS MONTHS

DURATION OF SEDATIVE – HYPNOTIC / BZD WDS

mild moderate bzd wds adrenergic autonomic
Mild-Moderate BZD WDS : Adrenergic / Autonomic
  • Anxiety
  • Restlessness / agitation
  • N/V, yawning
  • Insomnia
  • HT
  • Tachycardia
  • Mydriasis (dilated pupils)
severe bzd wds adrenergic autonomic
Severe BZD WDS : Adrenergic /Autonomic
  • Autonomic hyperactivity
  • Unstable vital signs
  • Hyperpyrexia (fever)
bzd wds musculoskeletal
BZD WDS : Musculoskeletal
  • Tremor
  • Weakness
  • Fasciculations
  • Spasms
  • Cramps
  • Hyperreflexia
bzd wds mild moderate neuropsychiatric
BZD WDS : Mild-Moderate Neuropsychiatric
  • Sensory
  • Hypersensitivity to
  • - light, sound, touch, smell
  • Light headedness / dizziness
  • Depression
  • Depersonalization
  • Confusion
  • Difficulty expressing thoughts
bzd wds severe neuropsychiatric s s s
BZD WDS : Severe Neuropsychiatric S&S’s
  • Psychosis
  • Delusions
  • Hallucinations
  • Mania
  • Catatonia
  • Delirium
  • SZ’s
bzd wds sort of sounds like aws doesn t it
BZD WDS : Sort of sounds like AWS, doesn’t it?
  • Both Etoh & BZD’s
  • Are GABA-receptor agonists
  • Whose WDS’s are really unopposed
  • Down-regulated GABA withdrawal syndrome (WDS)
sedative hypnotic wds
Sedative-Hypnotic WDS :
  • 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
Sedative-Hypnotic WDS : Severe Neuropsychiatric S&S’s
  • Delirium
  • Psychosis
  • Hallucinations
  • Hyperthermia
  • Cardiac arrest & death
sedative hypnotic wds1
Sedative-Hypnotic WDS :
  • Is essentially IDENTICAL to AWS
  • (Alcohol Withdrawal Syndrome)
  • Because BOTH
  • Etoh & BARB’s pharmacologically are
  • GABA receptor agonists &
  • NMDA-Glutamate receptor antagonists
sedative hypnotic wds2
Sedative-Hypnotic WDS :
  • 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
BZD WDS will exacerbate these comorbid conditions :
  • 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
BZD & Sedative-Hypnotic WDS Rx : INPT use ONLY
  • 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
BZD & Sedative-Hypnotic WDS Rx :
  • - 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 rx1
BZD & Sedative-Hypnotic WDS Rx :
  • 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 rx2
BZD & Sedative-Hypnotic WDS Rx :
  • 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 rx3
BZD & Sedative-Hypnotic WDS Rx :
  • Phenobarb 120mg x 1, then
  • 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

1st 24 hrs=390mg

bzd sedative hypnotic wds rx4
BZD & Sedative-Hypnotic WDS Rx :
  • 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
Case #5: Consult in ICU“The confused pt”
  • 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 pt1
Case #5: Consult in ICU“The confused pt”
  • 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 pt2
Case #5: Consult in ICU“The confused pt”
  • “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
Case #5: Consult in ICU“The confused staff”
  • 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
Case #5: the ICU pt &“The confused staff”
  • 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
Case #5: the ICU pt(the problem with the case)
  • 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 case1
Case #5: the ICU pt(the problem with the case)
  • 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.
slide97

2-KETO BZD’s

N-DESALKYLATED

COMPOUNDS

3-OH BZD’s

DEMOXEPAM

(Long)

TEMAZEPAM

(RESTORIL) (Int)

G

L

U

C

U

R

O

N

I

D

A

T

I

O

N

CHLORDIAZEPOXIDE

(LIBRIUM) (Intermediate)

DIAZEPAM

(VALIUM) (Long)

NORDIAZEPAM

(Long)

OXAZEPAM

(SERAX) (Int)

TRIAZOLO BZD’s

LORAZEPAM

(ATIVAN) (Int)

TRIAZOLAM

(HALCION) (Short)

ALPRAZOLAM

(XANAX) (Short)

ALPHA –OH’s

via oxidation

(Short)

7-NITRO BZD’s

Nitroreduction

& acetylation

(NO ACTIVE METABOLITE)

CLONAZEPAM

(KLONOPIN) (Long)

cocaine
Cocaine :
  • Pharmacokinetics :
  • T1/2 cocaine = 40-60 min
  • Metabolized by
  • - plasma cholinesterase to
  • - benzoylecgonine, found in urine
  • - up to 48 hrs, on UDS
cocaine intoxication
Cocaine Intoxication :
  • 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
CocaineIntoxication : Medical aspects
  • 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 intoxication1
CocaineIntoxication :
  • 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
Amphetamine & Methamphetamine (MA) :Intoxication
  • 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
Amphetamines / MAIntoxication :
  • Medical effects :
  • - HT, tachydysrythmias
  • - hyperthermia
  • - SZ’s
  • - malnutrition
  • - cerebral vasculitis
  • - orofacial dyskinesias

(remember the “binky” with MDMA)

psychomotor stimulant intoxication aminergic
Psychomotor StimulantIntoxication : (+) Aminergic
  • Restlessness, irritability, tremor
  • Talkativeness
  • Anxiety
  • Labile mood (esp. violence with MA)
  • HA
  • Chills, vomiting, diaphoresis
  • Delirium
psychomotor stimulant intoxication psychiatric
Psychomotor StimulantIntoxication : Psychiatric
  • - Hypervigilance
  • - Panic reactions
  • - Compulsive stereotypical behavior
  • - Paranoia
  • All of which is often referred to as,
  • “Tweaking”
psychomotor stimulant intoxication rx
Psychomotor StimulantIntoxication : Rx
  • (+) 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
Psychomotor Stimulant IntoxicationPsychosisRx :
  • 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
Cocaine, MA, or other stimulantWDS :
  • (+) “craving”
  • (+) depressed mood
  • (+) anhedonia
  • (+) pleasure deficiency syndrome
  • (+) fatigue
  • (+) hypersomnolence
cocaine ma or other stimulant wds cont d
Cocaine, MA, or other stimulantWDS (cont.d) :
  • 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
OWS “The flu” : Serotonergic/ Adrenergicsigns & symptoms
  • Myalgias & arthralgias
  • Dysphoria / Depressed mood
  • ANXIETY
  • Perspiration / diaphoresis
  • Fever
  • Exacerbation of ANY comorbid painful medical or orthopedic condition
ows the flu cholinergic signs symptoms
OWS “The flu” : Cholinergic signs & symptoms
  • Lacrimation
  • Rhinorrhea
  • Yawning
  • N/V
  • Diarrhea / intestinal CRAMPS
ows the flu dopaminergic signs symptoms
OWS “The flu” : Dopaminergic signs & symptoms
  • Anhedonia
  • Opioid craving
  • Opioid seeking behavior
case 6 the dea don t ever attempt
Case #6: “The DEA”(Don’t Ever Attempt)
  • 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
Case #6:ADM point of view:
  • 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
Case #6: Administering or Dispensing Narcotic Drugs
  • 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
Case #6:DEA point of view:
  • 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 view1
Case #6:DEA point of view:
  • 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
Case #7: “What shall I name my new hospital?”
  • 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 hospital1
Case #7: “What shall I name my new hospital?”
  • (+) 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
Case #7: What else could have been done?
  • 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 done1
Case #7: What else could have been done?
  • 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 done2
Case #7: What else could have been done?
  • 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
Case #7: Controlled Substances Act
  • 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
Case #7: 21 CFR 1306.07 (b) (cont’d.)
  • 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
And in closing,
  • I’m pleased we could spend this time together today.
  • Good luck on your Boards.
  • I’m grateful you were so attentive.
  • Thank you.
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