addiction medicine (adm) steven c. boles, d.o., fasam steven c. boles, d.o., fasam board certified -...
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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 Adjunct Clinical Faculty - Midwestern
University Arizona College of Osteopathic Medicine
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 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 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 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” 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 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 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
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
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”
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” 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”
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 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 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.
TIME hrs/DAY
M
T
D
10
20
30
40
50
60
70
80
90
100
0 12 1 12 2 12 3 12 4 12 5 12 6 12 7
110 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)
TIME hrs/DAY
M
T
D
10
20
30
40
50
60
70
80
90
100
0 12 1 12 2 12 3 12 4 12 5 12 6 12 7
110
INTOXICATED AND ALMOST DEAD FROM VENTILATORY FAILURE
NALTREXONE 12.5mg given
NALTREXONE 25mg given
Acute Alcohol Withdrawal Syndrome (AWS) :
Signs & Symptoms : Tachycardia HT Diaphoresis Insomnia Anxiety N/V
Acute AWS : symptoms & signs Tremor Generalized SZ’s Psychomotor agitation Hallucinosis/delusions (+/-
insight) DT’s
AWS : Hallucinosis
Visual : - lights too bright - animal life: dogs, rodents, bugs in
room
AWS : Hallucinosis
Auditory : - sounds too loud/startling - start out as unformed sounds clicking buzzing thumping from other room - may progress to formed voices
AWS : Hallucinosis
Auditory : Formed voices - friends/relatives - accusatory in nature In contrast to those of
schizophrenia : - religious - political
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 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) 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
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
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
(+) all S&S’s of mild AWS, only now
SEVERE : - tachycardia - HT - diaphoresis - tremor - fever
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.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 :
(+) BAL > 300 mg/dl at presentation
(+) AWS seizure (SZ) at presentation
AWS Rx :
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 :
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 : Two groups of pts : #1 = Elderly #2 = Significant liver disease - (GGT > 600) - underlying active viral hepatits
(HCV) - hepatic cirrhosis
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 Rx : In these pts, use Lorazepam (Ativan) Oxazepam (Serax) Because both drugs are ALREADY 3-OH BZD’s and therefore
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)
2-KETO BZD’s N-DESALKYLATEDCOMPOUNDS 3-OH BZD’s
CHLORDIAZEPOXIDE(LIBRIUM) (Intermediate)
DIAZEPAM(VALIUM) (Long)
TRIAZOLO BZD’s
TRIAZOLAM(HALCION) (Short)
ALPRAZOLAM(XANAX) (Short)
7-NITRO BZD’s
CLONAZEPAM(KLONOPIN) (Long)
DEMOXEPAM(Long)
NORDIAZEPAM(Long)
TEMAZEPAM(RESTORIL) (Int)
OXAZEPAM(SERAX) (Int)
LORAZEPAM(ATIVAN) (Int)
ALPHA –OH’svia oxidation
(Short)
Nitroreduction & acetylation (NO ACTIVE METABOLITE)
GLUCURONIDATION
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)
REMEMBER :
ALWAYS give Valium/Ativan BEFORE the Haldol, to eliminate/reduce risk of SZ’s from
haloperidol
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 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 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 : 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 ** 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
If not controlled with above, then Paralyze Completely sedate Intubate & ventilate Provide supportive ICU care Hope pt does not die
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 :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 ? 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? 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? 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?
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? 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? ANYONE who can operate a supertanker, with a BAL = 281 mg/dl, and not APPEAR DRUNK
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.
HALFTIME BREAK
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
WITHDRAWAL INTENSITY
ACUTE WDS HIGH DOSE, ANYLOW DOSESHORT ACTING
LOW DOSE LONG ACTING
PROLONGED POST ACUTE WDS (PAWS)
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: 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: 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: 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 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
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
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
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
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
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
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-DESALKYLATEDCOMPOUNDS 3-OH BZD’s
CHLORDIAZEPOXIDE(LIBRIUM) (Intermediate)
DIAZEPAM(VALIUM) (Long)
TRIAZOLO BZD’s
TRIAZOLAM(HALCION) (Short)
ALPRAZOLAM(XANAX) (Short)
7-NITRO BZD’s
CLONAZEPAM(KLONOPIN) (Long)
DEMOXEPAM(Long)
NORDIAZEPAM(Long)
TEMAZEPAM(RESTORIL) (Int)
OXAZEPAM(SERAX) (Int)
LORAZEPAM(ATIVAN) (Int)
ALPHA –OH’svia oxidation
(Short)
Nitroreduction & acetylation (NO ACTIVE METABOLITE)
GLUCURONIDATION
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
WITHDRAWAL INTENSITY
ACUTE WDS HIGH DOSE, ANYLOW DOSESHORT ACTING
LOW DOSE LONG ACTING
PROLONGED POST ACUTE WDS (PAWS)
Mild-Moderate BZD WDS : Adrenergic / Autonomic Anxiety Restlessness / agitation N/V, yawning Insomnia HT Tachycardia Mydriasis (dilated pupils)
Severe BZD WDS : Adrenergic /Autonomic Autonomic hyperactivity Unstable vital signs Hyperpyrexia (fever)
BZD WDS : Musculoskeletal Tremor Weakness Fasciculations Spasms Cramps Hyperreflexia
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 Psychosis Delusions Hallucinations Mania Catatonia Delirium SZ’s
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 :
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 Delirium Psychosis Hallucinations Hyperthermia Cardiac arrest & death
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 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 : 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
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 : - 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 : 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 : 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 : 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 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” 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” 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” “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” 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” 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) 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)
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-DESALKYLATEDCOMPOUNDS 3-OH BZD’s
CHLORDIAZEPOXIDE(LIBRIUM) (Intermediate)
DIAZEPAM(VALIUM) (Long)
TRIAZOLO BZD’s
TRIAZOLAM(HALCION) (Short)
ALPRAZOLAM(XANAX) (Short)
7-NITRO BZD’s
CLONAZEPAM(KLONOPIN) (Long)
DEMOXEPAM(Long)
NORDIAZEPAM(Long)
TEMAZEPAM(RESTORIL) (Int)
OXAZEPAM(SERAX) (Int)
LORAZEPAM(ATIVAN) (Int)
ALPHA –OH’svia oxidation
(Short)
Nitroreduction & acetylation (NO ACTIVE METABOLITE)
GLUCURONIDATION
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 :
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 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 :
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 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 : Medical effects : - HT, tachydysrythmias - hyperthermia - SZ’s - malnutrition - cerebral vasculitis - orofacial dyskinesias (remember the “binky” with
MDMA)
Psychomotor StimulantIntoxication : (+) Aminergic
Restlessness, irritability, tremor Talkativeness Anxiety Labile mood (esp. violence with MA) HA Chills, vomiting, diaphoresis Delirium
Psychomotor StimulantIntoxication : Psychiatric - Hypervigilance - Panic reactions - Compulsive stereotypical
behavior - Paranoia All of which is often referred to as, “Tweaking”
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 :
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 : (+) “craving” (+) depressed mood (+) anhedonia (+) pleasure deficiency syndrome (+) fatigue (+) hypersomnolence
Cocaine, MA, or other stimulant WDS (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
Myalgias & arthralgias Dysphoria / Depressed mood ANXIETY Perspiration / diaphoresis Fever Exacerbation of ANY comorbid
painful medical or orthopedic condition
OWS “The flu” : Cholinergic signs & symptoms Lacrimation Rhinorrhea Yawning N/V Diarrhea / intestinal CRAMPS
OWS “The flu” : Dopaminergic signs & symptoms
Anhedonia Opioid craving Opioid seeking behavior
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: 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 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: 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:
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?”
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?”
(+) 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?
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? 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?
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 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.) 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,
I’m pleased we could spend this time together today.
Good luck on your Boards. I’m grateful you were so
attentive. Thank you.