1. Addiction Medicine (ADM) Steven C. Boles, D.O., FASAM Steven C. Boles, D.O., FASAM Board Certified - FP Board Certified - FP ASAM Certified – ADM ASAM Certified – ADM Board = American Osteopathic Board of Board = American Osteopathic Board of Family Physicians Family Physicians ASAM = American Society of Addiction ASAM = American Society of Addiction Medicine Medicine Adjunct Clinical Faculty - Midwestern University Arizona College of Osteopathic Medicine Adjunct Clinical Faculty - Midwestern University Arizona College of Osteopathic Medicine

2. Case #1: “Don’t drink before surgery….” 45 y/o M, post-op ORIF femur fx 45 y/o M, post-op ORIF femur fx Becomes agitated, slightly febrile Becomes agitated, slightly febrile Remains tachycardic, on POD#2 Remains tachycardic, on POD#2 His last drink was 3 DAYS AGO 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 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 He is given 80mgs Valium PO that day But still pulls out his IV, wants to walk, and But still pulls out his IV, wants to walk, and Hears noises that aren’t there, per the RN. Hears noises that aren’t there, per the RN.

3. Case #1: “Don’t drink before surgery….” The pt at this point The pt at this point has not had his risk for alcohol withdrawal syndrome (AWS) recognized has not had his risk for alcohol withdrawal syndrome (AWS) recognized except possibly by the ER. except possibly by the ER. But that concern, Dx, and Rx But that concern, Dx, and Rx has not been followed-up on has not been followed-up on during all the attention during all the attention given his surgical problem. given his surgical problem.

4. Case #1: “Don’t drink before surgery….” The pt at this point has had The pt at this point has had partial Rx for AWS, partial Rx for AWS, blunting its development, blunting its development, but NOT preventing but NOT preventing the progression into the emergence the progression into the emergence of early delirium tremens. of early delirium tremens.

5. Case #1: “Don’t drink before surgery….” He hears noises that aren’t there, per RN. He hears noises that aren’t there, per RN. He is given IV Haldol 5mgs q 4hrs x 2 He is given IV Haldol 5mgs q 4hrs x 2 And calms down. And calms down. He receives Ativan & Haldol He receives Ativan & Haldol Over the next 48 hrs, in decreasing taper Over the next 48 hrs, in decreasing taper Goes home POD #5 Goes home POD #5

6. Case #1: “….., but if you do, always tell your doctor” REMEMBER : REMEMBER : Always give BZD’s BEFORE HALDOL Always give BZD’s BEFORE HALDOL To avoid SZ’s To avoid SZ’s And if Haldol is given IV, And if Haldol is given IV, Extrapyramidal side effects (EPS’s) Extrapyramidal side effects (EPS’s) Rarely, if ever, occur. Rarely, if ever, occur. And what is the top dose of IV Haldol (haloperidol) that may be given to a human being??????? And what is the top dose of IV Haldol (haloperidol) that may be given to a human being???????

7. Case #1: Alcohol Withdrawal Syndrome (AWS) & Thiamine Give thiamine 100mgs PO/IM/IV Give thiamine 100mgs PO/IM/IV BEFORE ANY GLUCOSE IV BEFORE ANY GLUCOSE IV To prevent precipitating : To prevent precipitating : - Wernicke’s encephalopathy - Wernicke’s encephalopathy - Korsakoff’s confabulatory amnestic - Korsakoff’s confabulatory amnestic psychosis psychosis

8. Case #1: AWS & Thiamine Give ALL pts at least 100 mg/day PO. Give ALL pts at least 100 mg/day PO. However, However, If alcoholic encephalopathy is present : If alcoholic encephalopathy is present : - give 200 mg TID, either PO or IV - give 200 mg TID, either PO or IV - for 4 WEEKS - for 4 WEEKS And how would one quickly test for this type of encephalopathy? And how would one quickly test for this type of encephalopathy?

9. CLINICALLY: Alcoholic Frontoparietal Hippocampal Encephalopathy Detection : simply add a small test to Detection : simply add a small test to the neuro exam the neuro exam Give them a pen and paper, and ask them to, “Draw me a clock that says 10 after 11, please.” 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 Takes 2 minutes or less You may be VERY surprised at the response from someone so talkative You may be VERY surprised at the response from someone so talkative

10. Case #1: AWS & Thiamine IF EITHER: IF EITHER: Wernicke’s encephalopathy, or Wernicke’s encephalopathy, or Korsakoff’s amnestic psychosis Korsakoff’s amnestic psychosis are present: are present: give 1000mg/day of thiamine x 4 wks give 1000mg/day of thiamine x 4 wks (that’s not a misprint) (that’s not a misprint)

11. Case #2: “Lying to your doctor can be fatal” 39 y/o F, (+)chronic pain, 39 y/o F, (+)chronic pain, Rx’d MTD (methadone) 40 mg/day, X 6 yrs, Rx’d MTD (methadone) 40 mg/day, X 6 yrs, presents for detox from BZD’s & cocaine (family angry w/her) presents for detox from BZD’s & cocaine (family angry w/her) Wants to stay on her methadone (MTD) Wants to stay on her methadone (MTD) States, “I was in jail for 3 days, States, “I was in jail for 3 days, and all they gave me was Risperdal, and all they gave me was Risperdal, and now I’m starting to have WD”. and now I’m starting to have WD”.

12. Case #2: “Lying to your doctor can be fatal” So, pt started on detox for cocaine/BZD So, pt started on detox for cocaine/BZD And, she is given her usual And, she is given her usual 40 mg MTD/day on day #1 of detox (20 mg BID) 40 mg MTD/day on day #1 of detox (20 mg BID) On day #2, pt mildly sedated, On day #2, pt mildly sedated, 3 hrs post 20mg AM MTD dose. 3 hrs post 20mg AM MTD dose. Total MTD = 60mg thus far Total MTD = 60mg thus far Prior to PM dose, pt is barely arousable (intoxicated), RR=6/min Prior to PM dose, pt is barely arousable (intoxicated), RR=6/min Passed out, lying sideways, across her bed. Passed out, lying sideways, across her bed.

13. Case #2: “Lying to your doctor can be fatal” What is the dose of methadone What is the dose of methadone that can fatal, that can fatal, if given to an opioid naïve pt? if given to an opioid naïve pt? According to Goodman & Gilman’s According to Goodman & Gilman’s “ The Pharmacological Basis of Therapeutics”, “ The Pharmacological Basis of Therapeutics”, (the King James’ version of pharmacology) (the King James’ version of pharmacology) it’s only 60mg. it’s only 60mg.

14. Case #2: “Lying to your doctor can be fatal” Brother verifies she was in jail for 6 wks. Brother verifies she was in jail for 6 wks. Given 12.5 mg naltrexone PO, Given 12.5 mg naltrexone PO, not naloxone (active by IV route). not naloxone (active by IV route). Pt simply wakes up, has some coffee, Pt simply wakes up, has some coffee, writes a letter (RR=22) and stays up all night. writes a letter (RR=22) and stays up all night. Additional 62.5 mg naltrexone given over next 3 days (MTD obviously DC’d). Additional 62.5 mg naltrexone given over next 3 days (MTD obviously DC’d).

15. Case #2: “Lying to your doctor can be fatal” Acutely precipitation of opioid withdrawal Acutely precipitation of opioid withdrawal DID NOT OCCUR, after an opioid antagonist was given in this case, DID NOT OCCUR, after an opioid antagonist was given in this case, As it would have, if her initial HX was true. As it would have, if her initial HX was true. And, by the way what did her MTD dosing curve look like??? And, by the way what did her MTD dosing curve look like??? After all, she was only given 3 identical 20mg doses. After all, she was only given 3 identical 20mg doses.

16. TIME hrs / DAY MTDMTD 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)

17. TIME hrs / DAY MTDMTD 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

18. Acute Alcohol Withdrawal Syndrome (AWS) : Signs & Symptoms : Signs & Symptoms : Tachycardia Tachycardia HT HT Diaphoresis Diaphoresis Insomnia Insomnia Anxiety Anxiety N/V N/V

19. Acute AWS : symptoms & signs Tremor Tremor Generalized SZ’s Generalized SZ’s Psychomotor agitation Psychomotor agitation Hallucinosis/delusions (+/- insight) Hallucinosis/delusions (+/- insight) DT’s DT’s

20. AWS : Hallucinosis Visual : Visual : - lights too bright - lights too bright - animal life: dogs, rodents, bugs in room - animal life: dogs, rodents, bugs in room

21. AWS : Hallucinosis Auditory : Auditory : - sounds too loud/startling - sounds too loud/startling - start out as unformed sounds - start out as unformed sounds clicking clicking buzzing buzzing thumping from other room thumping from other room - may progress to formed voices - may progress to formed voices

22. AWS : Hallucinosis Auditory : Auditory : Formed voices Formed voices - friends/relatives - friends/relatives - accusatory in nature - accusatory in nature In contrast to those of schizophrenia : In contrast to those of schizophrenia : - religious - religious - political - political

23. AWS : Delusions “I need to get dressed.” “I need to get dressed.” “I need go to work.” “I need go to work.” “I’ve got bills to pay.” “I’ve got bills to pay.” “I gotta get outa here.” “I gotta get outa here.”

24. Acute AWS begins when Etoh levels start to fall, if the pt is neuroadapted to ETOH Driven by : Driven by : Downregulation of inhibitory systems Downregulation of inhibitory systems Upregulation of excitatory systems Upregulation of excitatory systems Dysregulating LC : NE output Dysregulating LC : NE output Resultant hypernoradrenergic activity Resultant hypernoradrenergic activity From the brainstem. From the brainstem.

25. AWS : withdrawal seizures (WD SZ’s) Begin: 8 – 24 hrs AFTER LAST DRINK Begin: 8 – 24 hrs AFTER LAST DRINK May occur BEFORE a pt’s BAL=0 May occur BEFORE a pt’s BAL=0 Peak: 24 hrs after last drink Peak: 24 hrs after last drink Type: grand mal (generalized) Type: grand mal (generalized) singly, or in bursts singly, or in bursts over a period of 1 – 6 hrs over a period of 1 – 6 hrs Dilantin (phenytoin) is not effective Rx. Dilantin (phenytoin) is not effective Rx.

26. AWS : WD SZ’s Risk of occurrence in pt’s with : Risk of occurrence in pt’s with : genetic predisposition genetic predisposition (+)Hx of prior WD SZ’s (“kindling”) (+)Hx of prior WD SZ’s (“kindling”) undergoing concurrent WD from : undergoing concurrent WD from : - BZD’s - BZD’s - BARB’s - BARB’s - nonBARB sedatives (Soma / GHB) - nonBARB sedatives (Soma / GHB)

27. DT’s Generally appear 72 – 96 hrs Generally appear 72 – 96 hrs After last drink After last drink That’s 3 – 4 DAYS AFTER LAST DRINK That’s 3 – 4 DAYS AFTER LAST DRINK lasting for an lasting for an ADDITIONAL 2 – 3 DAYS (rare > 50 d) ADDITIONAL 2 – 3 DAYS (rare > 50 d) If someone starts into AWS + DT’s, If someone starts into AWS + DT’s, You’re looking at ONE WEEK. You’re looking at ONE WEEK.

28. CLASSIC DT’s (+) all S&S’s of mild AWS, only now (+) all S&S’s of mild AWS, only now SEVERE : SEVERE : - tachycardia - tachycardia - HT - HT - diaphoresis - diaphoresis - tremor - tremor - fever - fever

29. CLASSIC DT’s (cont.d) - global confusion - global confusion - absorbed in a separate psychic reality - absorbed in a separate psychic reality - believes him/her self to be in a - believes him/her self to be in a location other than hospital location other than hospital - may misidentify staff as - may misidentify staff as personal acquaintances personal acquaintances - hallucinations without insight - hallucinations without insight

30. CLASSIC DT’s (cont.d) - marked psychomotor agitation - marked psychomotor agitation - efforts to get out of bed - efforts to get out of bed LASTING FOR HOURS LASTING FOR HOURS - absence of clear sleep - absence of clear sleep LASTING FOR DAYS LASTING FOR DAYS Always monitor & Rx these pt’s Always monitor & Rx these pt’s IN AN ICU IN AN ICU

31. RISK OF DT’s : RISK OF DT’s : (+) BAL > 300 mg/dl at presentation (+) BAL > 300 mg/dl at presentation (+) AWS seizure (SZ) at presentation (+) AWS seizure (SZ) at presentation

32. AWS Rx : KEY : EARLY RX with BZD’s KEY : EARLY RX with BZD’s To PREVENT potentially FATAL DT’s To PREVENT potentially FATAL DT’s To shorten Rx time To shorten Rx time Increase pt safety & comfort Increase pt safety & comfort Prevent intercurrent medical complications Prevent intercurrent medical complications

33. BZD of choice : Use : DIAZEPAM (Valium), PO/IV Use : DIAZEPAM (Valium), PO/IV NEVER : IM NEVER : IM - variable absorbtion with - variable absorbtion with - slow/undependable onset - slow/undependable onset - delayed respiratory depression - delayed respiratory depression If IM BZD needed : LORAZEPAM (Ativan) If IM BZD needed : LORAZEPAM (Ativan) (Lorazepam may also be given IV) (Lorazepam may also be given IV)

34. Exception to Valium Rx : Two groups of pts : Two groups of pts : #1 = Elderly #1 = Elderly #2 = Significant liver disease #2 = Significant liver disease - (GGT > 600) - (GGT > 600) - underlying active viral hepatits (HCV) - underlying active viral hepatits (HCV) - hepatic cirrhosis - hepatic cirrhosis

35. Exception to Valium Rx : BOTH groups of pts have BOTH groups of pts have reduced BZD elimination, but reduced BZD elimination, but CYP oxidative pathways CYP oxidative pathways are reduced FAR MORE, than are reduced FAR MORE, than the glucuronide conjugation pathways. the glucuronide conjugation pathways.

36. Exception to Valium Rx : In these pts, use In these pts, use Lorazepam (Ativan) Lorazepam (Ativan) Oxazepam (Serax) Oxazepam (Serax) Because both drugs are Because both drugs are ALREADY 3-OH BZD’s ALREADY 3-OH BZD’s and therefore and therefore

37. Exception to Valium Rx : only require glucuronidation only require glucuronidation for elimination; and this avoids for elimination; and this avoids ACCUMULATION of toxic/sedating ACCUMULATION of toxic/sedating prodrug, or prodrug, or intermediate active metabolites, intermediate active metabolites, resulting from 2-keto BZD metabolism resulting from 2-keto BZD metabolism (Valium/Librium are 2-keto BZD’s) (Valium/Librium are 2-keto BZD’s)

38. 2-KETO BZD’s N-DESALKYLATED COMPOUNDS 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’s via oxidation (Short) Nitroreduction & acetylation (NO ACTIVE METABOLITE) GLUCURONIDATIONGLUCURONIDATION

39. REMEMBER : All BZD’s reduce AWS symptoms, but All BZD’s reduce AWS symptoms, but Diazepam, lorazepam, and clonazepam Diazepam, lorazepam, and clonazepam Are better ANTICONVULSANTS Are better ANTICONVULSANTS (because they have larger volumes of distribution, and are more lipophilic) (because they have larger volumes of distribution, and are more lipophilic) than either than either chlordiazepoxide (Librium), or chlordiazepoxide (Librium), or oxazepam (Serax) oxazepam (Serax)

40. REMEMBER : ALWAYS give Valium/Ativan ALWAYS give Valium/Ativan BEFORE the Haldol, BEFORE the Haldol, to eliminate/reduce risk of SZ’s from haloperidol to eliminate/reduce risk of SZ’s from haloperidol

41. AWS Rx : Structured BZD Dosing on med/surg floor DIAZEPAM : DIAZEPAM : - 20mg PO q 6 hrs x 4 doses, then - 20mg PO q 6 hrs x 4 doses, then - 10mg 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 - 5mg PO q 6 hrs x 4 doses, then DC Closely monitor pt Closely monitor pt Give additional doses, or hold doses, Give additional doses, or hold doses, prn prn

42. AWS Rx : Structured BZD Dosing on med/surg floor LORAZEPAM : LORAZEPAM : - 2mg PO or IV q 6 hrs x 4 doses, then - 2mg PO or IV q 6 hrs x 4 doses, then - 1mg 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 - 0.5mg PO or IV q 6 hrs x 4 doses, then DC Same precautions Same precautions

43. AWS Rx : Symptom- Triggered BZD Protocol on a Chemical Dependency (CD) Unit VALIUM : VALIUM : 5-20 mg PO q 1-2 hrs, prn CIWA-r scale 5-20 mg PO q 1-2 hrs, prn CIWA-r scale Usually results in : Usually results in : - 140mg Day #1 - 140mg Day #1 - 70mg Day #2 - 70mg Day #2 - 30mg Day #3 - 30mg Day #3 None, or 5mg last day None, or 5mg last day

44. AWS Rx : Symptom- Triggered BZD Protocol on a Chemical Dependency (CD) Unit

46. AWS Rx : Symptom- Triggered BZD Protocol If agitation : If agitation : - Ativan 2-4mg PO/IM q 6 hrs - Ativan 2-4mg PO/IM q 6 hrs If psychotic symptoms : If psychotic symptoms : - Ativan 2-4mg PO/IM q 6 hrs, then - Ativan 2-4mg PO/IM q 6 hrs, then - Haldol 2-5mg PO/IM q 6 hrs with - Haldol 2-5mg PO/IM q 6 hrs with - Benadryl 50mg PO/IM q 6 hrs - Benadryl 50mg PO/IM q 6 hrs If more than 1 dose Haldol given, then begin If more than 1 dose Haldol given, then begin - Cogentin 1mg PO q 12 hrs - Cogentin 1mg PO q 12 hrs

47. AWS Rx : DT’s ** Ativan 1mg IV + Haldol 2mg IV, then Ativan 1mg IV + Haldol 2mg IV, then Ativan 2mg IV + Haldol 3mg IV, then Ativan 2mg IV + Haldol 3mg IV, then Ativan 3mg IV + Haldol 5mg IV Ativan 3mg IV + Haldol 5mg IV Q 20 MIN, going up scale, Q 20 MIN, going up scale, IF NO RESPONSE to prior dose. IF NO RESPONSE to prior dose. May repeat scale q 2-3 hrs, prn May repeat scale q 2-3 hrs, prn Pt must be monitored in ICU Pt must be monitored in ICU

48. AWS Rx : DT’s If not controlled with above, then If not controlled with above, then Paralyze Paralyze Completely sedate Completely sedate Intubate & ventilate Intubate & ventilate Provide supportive ICU care Provide supportive ICU care Hope pt does not die Hope pt does not die

49. Etoh Pharmacology : Elimination Elimination Rate = 20 mg/dl, per hr, Elimination Rate = 20 mg/dl, per hr, in the serum, based on the BAL lab test. in the serum, based on the BAL lab test. The absolute amount of alcohol eliminated The absolute amount of alcohol eliminated from the body is 10 grams per hour, from the body is 10 grams per hour, or about the amount of alcohol in a “standard drink” or about the amount of alcohol in a “standard drink”

50. Etoh Pharmacology : Elimination (BAL) + (20)(hrs since last drink) = (BAL) + (20)(hrs since last drink) = Calculated BAL @ time of the last drink Calculated BAL @ time of the last drink Used to predict the SEVERITY of : Used to predict the SEVERITY of : - impending AWS - impending AWS - risk of DT’s, or SZ’s - risk of DT’s, or SZ’s during AWS. during AWS.

51. Is the Breathalyzer in agreement with BAL ? Breathalyzer result of 0.100 means: Breathalyzer result of 0.100 means: = 0.100 grams Etoh / 210 L of expired = 0.100 grams Etoh / 210 L of expired deep lung air deep lung air = (0.476 mg / L) = (0.05% of the BAL) = (0.476 mg / L) = (0.05% of the BAL) BAL = 950 mg / L BAL = 950 mg / L BAL = 95 mg / dl BAL = 95 mg / dl BAL ~ 100 mg/dl, i.e., legally drunk BAL ~ 100 mg/dl, i.e., legally drunk

52. Case #3: What’s the Dx? In the mid 1980’s, In the mid 1980’s, The supertanker, “Exxon Valdez” The supertanker, “Exxon Valdez” ran aground in Alaska. ran aground in Alaska. Captain Hazelwood’s BAL was Captain Hazelwood’s BAL was reported to be = 61 mg/dl reported to be = 61 mg/dl (Breathalyzer = 0.061) (Breathalyzer = 0.061)

53. Case #3: What’s the Dx? But it was drawn But it was drawn 11 hrs AFTER the grounding. 11 hrs AFTER the grounding. Retrograde extrapolation, Retrograde extrapolation, determined his BAL = 226mg/dl, determined his BAL = 226mg/dl, (Breathalyzer = 0.226) (Breathalyzer = 0.226) at the time of the accident, at the time of the accident, by Dr. David Smith, by Dr. David Smith, during his trial testimony. during his trial testimony.

54. Case #3: What’s the Dx? I would have calculated it as : I would have calculated it as : (11 hrs) x (20 mg/dl per hr) + ( 61 mg/dl ) (11 hrs) x (20 mg/dl per hr) + ( 61 mg/dl ) = 281 mg/dl BAL, = 281 mg/dl BAL, ( Breathalyzer = 0.281 ), ( Breathalyzer = 0.281 ), AT THE TIME OF THE OF THE ACCIDENT, AT THE TIME OF THE OF THE ACCIDENT, At the time of his last drink. At the time of his last drink. But they didn’t call me. But they didn’t call me.

55. Case #3: What’s the Dx? Either way, he was really drunk. Either way, he was really drunk. But the ever vigilant Coast Guard But the ever vigilant Coast Guard Never detected any signs of insobriety Never detected any signs of insobriety Other than the smell of alcohol. Other than the smell of alcohol.

56. Case #3: What’s the Dx? ANYONE who can ANYONE who can operate a supertanker, operate a supertanker, with a BAL = 281 mg/dl, with a BAL = 281 mg/dl, and not APPEAR DRUNK and not APPEAR DRUNK

57. Case #3: What’s the Dx? to the cop who arrested him, to the cop who arrested him, is neuroadapted to Etoh; is neuroadapted to Etoh; and, therefore his Dx is and, therefore his Dx is ALCOHOLISM. ALCOHOLISM. And he is also at a very high risk And he is also at a very high risk for alcohol withdrawal seizures for alcohol withdrawal seizures & subsequent DT’s. & subsequent DT’s.

58. HALFTIME BREAK

59. 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 INTENSITYWITHDRAWAL INTENSITY ACUTE WDS HIGH DOSE, ANY LOW DOSE SHORT ACTING LOW DOSE LONG ACTING PROLONGED POST ACUTE WDS (PAWS)

60. Case #4: Subpoenaed to provide testimony 47 y/o M crashes into parked cars in his neighborhood one afternoon 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 An 8-page report is generated by the arresting officer & DRE on the scene DRE = Drug Recognition Expert DRE = Drug Recognition Expert The report details the driver’s (your pt’s) condition at the time : The report details the driver’s (your pt’s) condition at the time :

61. Case #4: Subpoenaed to provide testimony - dilated pupils, bloodshot eyes - dilated pupils, bloodshot eyes - persistently elevated BP & pulse - persistently elevated BP & pulse - diaphoresis - diaphoresis - shaking, twitching, tremor - shaking, twitching, tremor - rapid speech, - rapid speech, - at times not making sense - at times not making sense - high anxiety level - high anxiety level

62. Case #4: Subpoenaed to provide testimony He is arrested for driving impaired, He is arrested for driving impaired, Under the influence OF A STIMULANT Under the influence OF A STIMULANT subsequent UDS/serum drug screen: subsequent UDS/serum drug screen: - acetylsalicylic acid - acetylsalicylic acid - cotinine - cotinine - caffeine - caffeine - nordiazepam - nordiazepam

63. Case #4: Subpoenaed to provide testimony You prescribed You prescribed Librium (chlordiazepoxide) Librium (chlordiazepoxide) 2 months previously, to help him 2 months previously, to help him stop drinking after he was released stop drinking after he was released from jail for a DUI. from jail for a DUI. His defense attorney would like you to explain ANY of this at trial, if you can. His defense attorney would like you to explain ANY of this at trial, if you can.

64. Case #4: At trial, on the witness stand You look at the forensic lab tech, and note her fine & accurate work. You look at the forensic lab tech, and note her fine & accurate work. You tell the judge & jury that the drugs represent : You tell the judge & jury that the drugs represent : Cigarettes (cotinine metabolite); Cigarettes (cotinine metabolite); Aspirin (acetylsalicylic acid); Aspirin (acetylsalicylic acid); Coffee (caffeine); and Coffee (caffeine); and Librium (nordiazepam metabolite). Librium (nordiazepam metabolite).

65. Case #4: On the stand You explain to them that nordiazepam is psychoactive by-product of Librium You explain to them that nordiazepam is psychoactive by-product of Librium and that both are sedatives/tranquilizers. 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). 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. He proudly returns your gaze.

66. Case #4: On the stand You also agree, in your expert opinion, that the pt was indeed You also agree, in your expert opinion, that the pt was indeed under the influence of a stimulant, at the time of the accident. under the influence of a stimulant, at the time of the accident. But, that the stimulant was the natural norepinephrine IN HIS BRAIN, But, that the stimulant was the natural norepinephrine IN HIS BRAIN, and not any illicit substance, and not any illicit substance, since none was detected since none was detected upon forensic testing. upon forensic testing.

67. Case #4: On the stand You look at the at everyone in the courtroom, and explain the You look at the at everyone in the courtroom, and explain the ONLY POSSIBLE EXPLANATION FOR THESE FACTS ONLY POSSIBLE EXPLANATION FOR THESE FACTS are that the alcoholic defendant are that the alcoholic defendant was in early DT’s from AWS, was in early DT’s from AWS, and even though this is very dangerous, and even though this is very dangerous, it is not against the law. it is not against the law.

68. Case #4: On the stand You look back to the DRE, and he You look back to the DRE, and he looks down at all his hard work, looks down at all his hard work, and almost starts to cry. and almost starts to cry. You also explain that the pt was clearly You also explain that the pt was clearly not under the influence of a not under the influence of a tranquilizer, and in fact, if he had taken tranquilizer, and in fact, if he had taken MORE Librium, he wouldn’t have had MORE Librium, he wouldn’t have had the accident in the first place. the accident in the first place.

69. Case #4: On the stand You further comment that the T1/2 of You further comment that the T1/2 of Librium = 100 hrs (4 days) Librium = 100 hrs (4 days) Nordiazepam = 200 hrs (8 days) Nordiazepam = 200 hrs (8 days) especially in someone with early cirrhosis. especially in someone with early cirrhosis. And that it takes ~ 10-12 T1/2’s And that it takes ~ 10-12 T1/2’s to clear any drug from the body, to clear any drug from the body, explaining the (+) UDS, 60 days later. explaining the (+) UDS, 60 days later.

70. Case #4: On the stand Also note: Also note: There was NO PARENT COMPOUND found on the UDS There was NO PARENT COMPOUND found on the UDS There was no chlordiazepoxide There was no chlordiazepoxide Only its metabolite, nordiazepam Only its metabolite, nordiazepam Indicating this WAS NOT an acute intoxication reaction from the Librium Indicating this WAS NOT an acute intoxication reaction from the Librium

71. 2-KETO BZD’s N-DESALKYLATED COMPOUNDS 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’s via oxidation (Short) Nitroreduction & acetylation (NO ACTIVE METABOLITE) GLUCURONIDATIONGLUCURONIDATION

72. 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 INTENSITYWITHDRAWAL INTENSITY ACUTE WDS HIGH DOSE, ANY LOW DOSE SHORT ACTING LOW DOSE LONG ACTING PROLONGED POST ACUTE WDS (PAWS)

73. Mild-Moderate BZD WDS : Adrenergic / Autonomic Anxiety Anxiety Restlessness / agitation Restlessness / agitation N/V, yawning N/V, yawning Insomnia Insomnia HT HT Tachycardia Tachycardia Mydriasis (dilated pupils) Mydriasis (dilated pupils)

74. Severe BZD WDS : Adrenergic /Autonomic Autonomic hyperactivity Autonomic hyperactivity Unstable vital signs Unstable vital signs Hyperpyrexia (fever) Hyperpyrexia (fever)

75. BZD WDS : Musculoskeletal Tremor Tremor Weakness Weakness Fasciculations Fasciculations Spasms Spasms Cramps Cramps Hyperreflexia Hyperreflexia

76. BZD WDS : Mild-Moderate Neuropsychiatric Sensory Sensory Hypersensitivity to Hypersensitivity to - light, sound, touch, smell - light, sound, touch, smell Light headedness / dizziness Light headedness / dizziness Depression Depression Depersonalization Depersonalization Confusion Confusion Difficulty expressing thoughts Difficulty expressing thoughts

77. BZD WDS : Severe Neuropsychiatric S&S’s Psychosis Psychosis Delusions Delusions Hallucinations Hallucinations Mania Mania Catatonia Catatonia Delirium Delirium SZ’s SZ’s

78. BZD WDS : Sort of sounds like AWS, doesn’t it? Both Etoh & BZD’s Both Etoh & BZD’s Are GABA-receptor agonists Are GABA-receptor agonists Whose WDS’s are really unopposed Whose WDS’s are really unopposed Down-regulated GABA withdrawal syndrome (WDS) Down-regulated GABA withdrawal syndrome (WDS)

79. Sedative-Hypnotic WDS : Will occur after prolonged, high-dose exposure, & neuroadaptation, to any of the following: Will occur after prolonged, high-dose exposure, & neuroadaptation, to any of the following: Non-BARB / Non-BZD meds : e.g. Non-BARB / Non-BZD meds : e.g. - Chloral hydrate (Noctec) - Chloral hydrate (Noctec) - Meprobamate (Equanil, Miltown) - Meprobamate (Equanil, Miltown) - Carisopradol (Soma) - Carisopradol (Soma) Or Or any similarly dosed BARBITURATE any similarly dosed BARBITURATE

80. Sedative-Hypnotic WDS : Severe Neuropsychiatric S&S’s Delirium Delirium Psychosis Psychosis Hallucinations Hallucinations Hyperthermia Hyperthermia Cardiac arrest & death Cardiac arrest & death

81. Sedative-Hypnotic WDS : Is essentially IDENTICAL to AWS Is essentially IDENTICAL to AWS (Alcohol Withdrawal Syndrome) (Alcohol Withdrawal Syndrome) Because BOTH Because BOTH Etoh & BARB’s pharmacologically are Etoh & BARB’s pharmacologically are GABA receptor agonists & GABA receptor agonists & NMDA-Glutamate receptor antagonists NMDA-Glutamate receptor antagonists

82. Sedative-Hypnotic WDS : Is essentially IDENTICAL to AWS Is essentially IDENTICAL to AWS Because after neuroadaptation, Because after neuroadaptation, Both syndromes represent the newly unopposed pathologic effect of Both syndromes represent the newly unopposed pathologic effect of Down-regulated GABA receptors Down-regulated GABA receptors Combined with Combined with Up-regulated NMDA-Glu receptors Up-regulated NMDA-Glu receptors

83. BZD WDS will exacerbate these comorbid conditions : CAD / cardiac dysrhythmias / CV disease CAD / cardiac dysrhythmias / CV disease Asthma Asthma SLE SLE Inflammatory bowel disease Inflammatory bowel disease Severe NIDDM/IDDM Severe NIDDM/IDDM Severe arthritis Severe arthritis Severe thyroid disease Severe thyroid disease

84. BZD & Sedative-Hypnotic WDS Rx : INPT use ONLY Phenobarb substitution method : Phenobarb substitution method : - compute PB equivalent dose/day - compute PB equivalent dose/day - note: this is NOT same as therapeutic - note: this is NOT same as therapeutic dose equivalency, dose equivalency, - but it will prevent severe WDS - but it will prevent severe WDS

85. BZD & Sedative-Hypnotic WDS Rx : - DRUG : PHENOBARBITAL EQUIVALENT - DRUG : PHENOBARBITAL EQUIVALENT - Xanax 1mg : PB 30mg - Xanax 1mg : PB 30mg - Klonopin 2mg : PB 30mg - Klonopin 2mg : PB 30mg - Valium 10mg : PB 30mg - Valium 10mg : PB 30mg - Fiorinal 2 tabs : PB 30mg - Fiorinal 2 tabs : PB 30mg - Soma 2 tabs : PB 30mg - Soma 2 tabs : PB 30mg - Ativan 2mg : PB 30mg - Ativan 2mg : PB 30mg

86. BZD & Sedative-Hypnotic WDS Rx : The MAXIMUM STARTING DOSE of PB The MAXIMUM STARTING DOSE of PB Is 500mg/day Is 500mg/day The computed PB equivalent The computed PB equivalent Is given in divided doses TID / QID Is given in divided doses TID / QID And reduced by about 30mg per day, And reduced by about 30mg per day, With dose titration up, or down, PRN With dose titration up, or down, PRN

87. BZD & Sedative-Hypnotic WDS Rx : A pt taking A pt taking Xanax 6mg/day, plus Xanax 6mg/day, plus Soma 8/day, plus Soma 8/day, plus 6 pack of beer/day 6 pack of beer/day Gets : 6 + 4 + 3 = 13 PBE’s Gets : 6 + 4 + 3 = 13 PBE’s = 13 x 30mg PB = 13 x 30mg PB = 390mg PB day #1 = 390mg PB day #1

88. BZD & Sedative-Hypnotic WDS Rx : Phenobarb 120mg x 1, then Phenobarb 120mg x 1, then 90mg q 6hr x 3 doses, then 90mg q 6hr x 3 doses, then 75mg q 6hr x 4 doses, then 75mg q 6hr x 4 doses, then 60mg q 6hr x 4 doses, then 60mg q 6hr x 4 doses, then 60mg q 8hr x 3 doses, then 60mg q 8hr x 3 doses, then 45mg q 8hr x 3 doses, then 45mg q 8hr x 3 doses, then 30mg q 8hr x 3 doses, then 30mg q 8hr x 3 doses, then 15mg q 12hr x 2 doses, then DC 15mg q 12hr x 2 doses, then DC 1 st 24 hrs=390mg

89. BZD & Sedative-Hypnotic WDS Rx : Observe pt for any of the 3 signs of toxicity before each dose of PB : Observe pt for any of the 3 signs of toxicity before each dose of PB : - nystagmus - nystagmus - ataxia - ataxia - dysarthria - dysarthria If any 1 present, skip 1 dose If any 1 present, skip 1 dose If any 2 present, skip 2 doses If any 2 present, skip 2 doses

90. Case #5: Consult in ICU “The confused pt” They want to know if there are any drug WDS They want to know if there are any drug WDS that produce obtundation, or coma, that produce obtundation, or coma, on the 3 rd -4 th day on the 3 rd -4 th day after doing well the first 2 days? after doing well the first 2 days? 42 y/o M, came in agitated, paranoid, hallucinating. 42 y/o M, came in agitated, paranoid, hallucinating. (+) known “heavy drinker/IVDU” (+) known “heavy drinker/IVDU” UDS = (+) AMPHET only UDS = (+) AMPHET only

91. Case #5: Consult in ICU “The confused pt” BAL = 0 BAL = 0 (+) elevated vital signs (+) elevated vital signs (+) ALT= 112, AST= 84, GGT=213 (+) ALT= 112, AST= 84, GGT=213 Alb=3.4, Bili=2.1 (other labs WNL) Alb=3.4, Bili=2.1 (other labs WNL) “We followed the CD protocol, to prevent suspected AWS & DT’s. “We followed the CD protocol, to prevent suspected AWS & DT’s. Now it’s the 4 th day he’s been in ICU; his vitals are OK, but we can’t wake him up.” Now it’s the 4 th day he’s been in ICU; his vitals are OK, but we can’t wake him up.”

92. Case #5: Consult in ICU “The confused pt” “Really. “Really. “Exactly what did you give him?” “Exactly what did you give him?” “He had 4mg Ativan & 3mg Haldol in ER. “He had 4mg Ativan & 3mg Haldol in ER. We gave him, let’s see, a total of 70mg Valium over the first 36 hrs.” 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. “I see. Well, it does look like you followed the protocol, ……sort of. You just forgot one very important thing.” You just forgot one very important thing.”

93. Case #5: Consult in ICU “The confused staff” There are no WDS’s that progress to coma/obtundation There are no WDS’s that progress to coma/obtundation (severe BZD WDS may include catatonia, but not coma) (severe BZD WDS may include catatonia, but not coma) Pt had: Stimulant Intoxication Psychosis, Pt had: Stimulant Intoxication Psychosis, evidenced by UDS (+) for AMPHETAMINE evidenced by UDS (+) for AMPHETAMINE WHEN HAVING PSYCHOTIC SYMPTOMS. WHEN HAVING PSYCHOTIC SYMPTOMS. Additionally, Additionally,

94. Case #5: the ICU pt & “The confused staff” He ALSO was at risk for, or simultaneously in, DT’s. He ALSO was at risk for, or simultaneously in, DT’s. (a very bad combination). (a very bad combination). He had hepatic insufficiency, per labs, He had hepatic insufficiency, per labs, with ALD (alcoholic liver disease), with ALD (alcoholic liver disease), superimposed on superimposed on chronic active HCV hepatitis. chronic active HCV hepatitis. (another VERY bad combination). (another VERY bad combination).

95. Case #5: the ICU pt (the problem with the case) Suspected by ALT > AST (confirmed later by additional Hx, & (+) HCV Ab) Suspected by ALT > AST (confirmed later by additional Hx, & (+) HCV Ab) The problem was not recognizing the severity of his liver disease / oxidative deficiency, The problem was not recognizing the severity of his liver disease / oxidative deficiency, compounded by giving him a 2-keto BZD (Valium), compounded by giving him a 2-keto BZD (Valium), instead of a 3-OH BZD instead of a 3-OH BZD (Ativan / Serax). (Ativan / Serax).

96. Case #5: the ICU pt (the problem with the case) Leading to accumulation of : Leading to accumulation of : - unmetabolized diazepam, and it’s active - unmetabolized diazepam, and it’s active metabolite, metabolite, - desmethyldiazepam (nordiazepam). - desmethyldiazepam (nordiazepam). Both of which have T1/2’s of about 100 hrs (4 days), Both of which have T1/2’s of about 100 hrs (4 days), and both are psychoactive CNS depressants. and both are psychoactive CNS depressants. I told them to DC the Valium, I told them to DC the Valium, and he’d wake up in 2 weeks. and he’d wake up in 2 weeks.

97. 2-KETO BZD’s N-DESALKYLATED COMPOUNDS 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’s via oxidation (Short) Nitroreduction & acetylation (NO ACTIVE METABOLITE) GLUCURONIDATIONGLUCURONIDATION

98. Cocaine : Pharmacokinetics : Pharmacokinetics : T1/2 cocaine = 40-60 min T1/2 cocaine = 40-60 min Metabolized by Metabolized by - plasma cholinesterase to - plasma cholinesterase to - benzoylecgonine, found in urine - benzoylecgonine, found in urine - up to 48 hrs, on UDS - up to 48 hrs, on UDS

99. Cocaine Intoxication : Psychiatric effects : Psychiatric effects : (+) mimics naturally occurring mania (+) mimics naturally occurring mania Cocaine induced paranoia is usually distinguished by drug content on UDS Cocaine induced paranoia is usually distinguished by drug content on UDS May precipitate, or exacerbate May precipitate, or exacerbate - major psychiatric Dx’s - major psychiatric Dx’s

100. Cocaine Intoxication : Medical aspects Cardioventricular tachydysrythmias Cardioventricular tachydysrythmias Acute MI / Aortic dissection Acute MI / Aortic dissection Vasospasm, thrombosis, ischemia, necrosis (any organ, e.g. retinal artery) Vasospasm, thrombosis, ischemia, necrosis (any organ, e.g. retinal artery) Asthma / pulmonary dysfunction with melanoptysis (“crack lung”) Asthma / pulmonary dysfunction with melanoptysis (“crack lung”) Pneumomediastinum / pneumothorax Pneumomediastinum / pneumothorax Intrauterine / placenta abruptio Intrauterine / placenta abruptio

101. Cocaine Intoxication : Psychiatric effects : Psychiatric effects : (+) mimics naturally occurring mania (+) mimics naturally occurring mania Cocaine induced paranoia is usually distinguished by drug content on UDS Cocaine induced paranoia is usually distinguished by drug content on UDS May precipitate, or exacerbate May precipitate, or exacerbate Almost any major psychiatric Diagnosis Almost any major psychiatric Diagnosis

102. Amphetamine & Methamphetamine (MA) : Intoxication Repeated administration may cause : Repeated administration may cause : - paranoid psychosis - paranoid psychosis - stereotypical behaviors with repeated - stereotypical behaviors with repeated touching / picking / bruxism touching / picking / bruxism during the intoxication phase, during the intoxication phase, but not the withdrawal phase. but not the withdrawal phase.

103. Amphetamines / MA Intoxication : Medical effects : Medical effects : - HT, tachydysrythmias - HT, tachydysrythmias - hyperthermia - hyperthermia - SZ’s - SZ’s - malnutrition - malnutrition - cerebral vasculitis - cerebral vasculitis - orofacial dyskinesias - orofacial dyskinesias (remember the “binky” with MDMA) (remember the “binky” with MDMA)

104. Psychomotor Stimulant Intoxication : (+) Aminergic Restlessness, irritability, tremor Restlessness, irritability, tremor Talkativeness Talkativeness Anxiety Anxiety Labile mood (esp. violence with MA) Labile mood (esp. violence with MA) HA HA Chills, vomiting, diaphoresis Chills, vomiting, diaphoresis Delirium Delirium

105. Psychomotor Stimulant Intoxication : Psychiatric - Hypervigilance - Hypervigilance - Panic reactions - Panic reactions - Compulsive stereotypical behavior - Compulsive stereotypical behavior - Paranoia - Paranoia All of which is often referred to as, All of which is often referred to as, “Tweaking” “Tweaking”

106. Psychomotor Stimulant Intoxication : Rx (+) Agitation / anxiety : (+) Agitation / anxiety : - Ativan 1-2 mg IV/IM/PO q 30-60 min - Ativan 1-2 mg IV/IM/PO q 30-60 min - Valium 10-30 mg PO q 30-60 min - Valium 10-30 mg PO q 30-60 min

107. Psychomotor Stimulant Intoxication Psychosis Rx : Ativan 1mg IV + Haldol 2mg IV, then Ativan 1mg IV + Haldol 2mg IV, then Ativan 2mg IV + Haldol 3mg IV, then Ativan 2mg IV + Haldol 3mg IV, then Ativan 3mg IV + Haldol 5mg IV Ativan 3mg IV + Haldol 5mg IV Q 20 MIN, going up scale, Q 20 MIN, going up scale, if no response to prior dose. if no response to prior dose. May repeat scale q 2-3 hrs, prn May repeat scale q 2-3 hrs, prn Pt must be monitored in ICU Pt must be monitored in ICU (Just like treating DT’s, isn’t it?) (Just like treating DT’s, isn’t it?)

108. Cocaine, MA, or other stimulant WDS : (+) “craving” (+) “craving” (+) depressed mood (+) depressed mood (+) anhedonia (+) anhedonia (+) pleasure deficiency syndrome (+) pleasure deficiency syndrome (+) fatigue (+) fatigue (+) hypersomnolence (+) hypersomnolence

109. Cocaine, MA, or other stimulant WDS (cont.d) : THERE IS NO SPECIFIC DRUG Rx REQUIRED, THERE IS NO SPECIFIC DRUG Rx REQUIRED, BUT IF PSYCHOTIC SYMPTOMS PERSIST BEYOND 4 DAYS, BUT IF PSYCHOTIC SYMPTOMS PERSIST BEYOND 4 DAYS, THEN ANTIDEPRESANTS OR ANTIPSYCHOTICS THEN ANTIDEPRESANTS OR ANTIPSYCHOTICS MAY BE INDICATED MAY BE INDICATED

110. OWS “The flu” : Serotonergic/ Adrenergic signs & symptoms Myalgias & arthralgias Myalgias & arthralgias Dysphoria / Depressed mood Dysphoria / Depressed mood ANXIETY ANXIETY Perspiration / diaphoresis Perspiration / diaphoresis Fever Fever Exacerbation of ANY comorbid painful medical or orthopedic condition Exacerbation of ANY comorbid painful medical or orthopedic condition

111. OWS “The flu” : Cholinergic signs & symptoms Lacrimation Lacrimation Rhinorrhea Rhinorrhea Yawning Yawning N/V N/V Diarrhea / intestinal CRAMPS Diarrhea / intestinal CRAMPS

112. OWS “The flu” : Dopaminergic signs & symptoms Anhedonia Anhedonia Opioid craving Opioid craving Opioid seeking behavior Opioid seeking behavior

113. Case #6: “The DEA” (Don’t Ever Attempt) 27 y/o F, (+)ODS, presents to the office, 27 y/o F, (+)ODS, presents to the office, Desiring detox from smoking heroin. Desiring detox from smoking heroin. Percocet & Ativan are prescribed for detox, Percocet & Ativan are prescribed for detox, and she is told to continue attending AA. and she is told to continue attending AA. Anything wrong with this treatment? Anything wrong with this treatment? 2 weeks later, she presents for inpt detox 2 weeks later, she presents for inpt detox What went wrong? What went wrong?

114. Case #6: ADM point of view: Never give prn mood altering meds to Never give prn mood altering meds to an addict, and expect him/her an addict, and expect him/her to control them. to control them. After all, their disease is characterized by After all, their disease is characterized by LOSS OF CONTROL OVER USE. LOSS OF CONTROL OVER USE. The treatment can, therefore, The treatment can, therefore, be reasonably expected to fail. be reasonably expected to fail.

115. Case #6: Administering or Dispensing Narcotic Drugs 21 CFR (1306.07) : 21 CFR (1306.07) : To AMINISTER, or DISPENSE To AMINISTER, or DISPENSE (BUT NOT PRESCRIBE), (BUT NOT PRESCRIBE), narcotic drugs to a narcotic dependent person for “detoxification treatment”, or “maintenance treatment”, a physician narcotic drugs to a narcotic dependent person for “detoxification treatment”, or “maintenance treatment”, a physician MUST HAVE A SEPARATE REGISTRATION MUST HAVE A SEPARATE REGISTRATION with the attorney general. with the attorney general. [Sec. 303 (g) of the Act (21 U.S.C. 823 (g)] [Sec. 303 (g) of the Act (21 U.S.C. 823 (g)]

116. Case #6: DEA point of view: Traditionally, treating addiction to opiates Traditionally, treating addiction to opiates with opioids (methadone) with opioids (methadone) without a separate DEA registration without a separate DEA registration as a Narcotic Treatment Program, as a Narcotic Treatment Program, (that means being a methadone clinic) (that means being a methadone clinic)

117. Case #6: DEA point of view: Or without having a waiver from SAMHSA to prescribe buprenorphine Or without having a waiver from SAMHSA to prescribe buprenorphine (Suboxone or Subutex) (Suboxone or Subutex) is not included in the CSA, is not included in the CSA, and therefore, such activity is and therefore, such activity is OUTSIDE OUTSIDE THE SCOPE OF MEDICAL PRACTICE, THE SCOPE OF MEDICAL PRACTICE, AND THEREFORE, IS ILLEGAL. AND THEREFORE, IS ILLEGAL.

118. Case #7: “What shall I name my new hospital?” A 29 y/o pt (+)ODS, A 29 y/o pt (+)ODS, In methadone (MTD) clinic, In methadone (MTD) clinic, presents on a weekend, to ER, presents on a weekend, to ER, claiming her MTD take-home dose claiming her MTD take-home dose is lost, stolen, wasn’t picked up, etc….. is lost, stolen, wasn’t picked up, etc….. The pt has no other medical problems. The pt has no other medical problems. “I’m afraid of having MTD withdrawal.” “I’m afraid of having MTD withdrawal.”

119. Case #7: “What shall I name my new hospital?” (+) anxiety, elevated vitals are noted. (+) anxiety, elevated vitals are noted. The pt was given Ativan & clonidine, The pt was given Ativan & clonidine, and then DC’d to home by POV. and then DC’d to home by POV. Was this a good idea? Was this a good idea? No. No. The pt promptly took all of their meds The pt promptly took all of their meds at one time; and then promptly, at one time; and then promptly, “Fell asleep at the wheel”, “Fell asleep at the wheel”, and rolled their vehicle several times. and rolled their vehicle several times.

120. 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. 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, Absent signs & symptoms of OWS, NO Dx could have been made, other than ODS, and NO Rx would be indicated. NO Dx could have been made, other than ODS, and NO Rx would be indicated. Additionally, in this pt’s case, Additionally, in this pt’s case, a UDS should confirm the presence of MTD, if MTD was taken within 2-3 days. a UDS should confirm the presence of MTD, if MTD was taken within 2-3 days.

121. Case #7: What else could have been done? Note: the UDS employed must be able to detect MTD, Note: the UDS employed must be able to detect MTD, as MTD does NOT GIVE A (+) RESULT AS AN “OPIATE” ON A SCREENING TEST. as MTD does NOT GIVE A (+) RESULT AS AN “OPIATE” ON A SCREENING TEST. MTD is reported as “MTD”. MTD is reported as “MTD”. Remember MTD is structurally different from MS/codeine (opiates), and other synthetic opioids. Remember MTD is structurally different from MS/codeine (opiates), and other synthetic opioids. Remember the signs & symptoms of OWS Remember the signs & symptoms of OWS

122. Case #7: What else could have been done? ADMINISTER 15mg MTD PO / IM x 1 dose ADMINISTER 15mg MTD PO / IM x 1 dose Observe for relief of OWS at 3 hrs post dose, Observe for relief of OWS at 3 hrs post dose, and document findings. and document findings. Arrange for referral to treatment center. Arrange for referral to treatment center. Instruct pt to return the following day Instruct pt to return the following day To determine if another MTD dose should be administered (but not prescribed). To determine if another MTD dose should be administered (but not prescribed). DO NOT PRESCRIBE OR DISPENSE ANY OPIODS DO NOT PRESCRIBE OR DISPENSE ANY OPIODS Under what authority can this be done? Under what authority can this be done?

123. Case #7: Controlled Substances Act Same law: 21 CFR 1306.07 (b) 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 “Nothing in this section of the law shall prohibit a practitioner who is not specifically registered to conduct a NTP From ADMINISTERING From ADMINISTERING (BUT NOT PRESCRIBING) narcotic drugs (BUT NOT PRESCRIBING) narcotic drugs To a narcotic dependant person To a narcotic dependant person for the purposes of relieving for the purposes of relieving acute withdrawal symptoms when necessary acute withdrawal symptoms when necessary

124. Case #7: 21 CFR 1306.07 (b) (cont’d.) while arrangements are being made while arrangements are being made for referral for treatment. for referral for treatment. Not more than one day’s medication Not more than one day’s medication may be ADMINISTERED may be ADMINISTERED to the person AT ONE TIME. to the person AT ONE TIME. Such emergency treatment may be carried out Such emergency treatment may be carried out for NOT MORE THAN 3 DAYS, for NOT MORE THAN 3 DAYS, and MAY NOT BE RENEWED or extended”. and MAY NOT BE RENEWED or extended”.

125. And in closing, I’m pleased we could spend this time together today. I’m pleased we could spend this time together today. Good luck on your Boards. Good luck on your Boards. I’m grateful you were so attentive. I’m grateful you were so attentive. Thank you. Thank you.