Substance Use Disorder

SUBSTANCE USE DISORDER Parna Haghparast, PharmD, BCPS Associate Professor, Pharmacy Practice West Coast University Phaghparast@westcoastuniversity.edu menuse morealcohol Alcohol is not a stimulant DEFINITIONS Binge Drinking t Drinking that leads to BAC ≥ 0.08 (NIAAA) eat • Women: ≥ 4 drinks in 2 hrs • Men: ≥ 5 drinks in 2 hrs drinks postodard ≥ 5 drinks on the same occasion on at least 1 day in the past 30 days (SAMHSA) Heavy Drinking Binge drinking ≥ 5 days in the past 30 days (SAMHSA) e hasNJdifferentiate betweenmenor female 9 NIAAA, 2018 NIAAA:National Institute on Alcohol Abuse and Alcoholism SAMSHA: Substance Abuse and Mental Health Services Administration TRIVIA QUESTION 1  The amount of pure alcohol in a standard drink of beer, glass of wine, or shot of spirit is the same x True False 10 HOW LONG DOES ALCOHOL STAY IN YOUR BLOOD?  On average, 1 standard drink takes 1 hour to metabolize  This, however, varies by Weight 2 S Presence of Food 3 Metabolism/liver disease Gender 6 Concurrent Medications y Age 7 Type/Strength of Alcohol 11 NHS, 2019 FUN FACTS • 1 unit of alcohol = 10 ml (0.34 fl oz) or 8 g of pure alcohol • 1 standard drink = 1.75 units of alcohol = 14 g pure alcohol • 1 fl oz= 29.5 ml 12 NHS, 2019 CDC. Frequently Asked Questions. 2016 ALCOHOL INTOXICATION: ACUTE EFFECTS 0.02-0.03 No loss of coordination, slight euphoria, loss of shyness 0.04-0.06 Feeling of well-being, relaxation, lower inhibitions, sensation of warmth, euphoria. Some impairment of reasoning and memory, lowering of caution O 0.07-0.09 Slight impairment of balance, speech, vision, reaction time, and hearing, euphoria. Judgment and self-control are reduced, and caution, reason, and memory are impaired. 0.10-0.125 Significant impairment of motor coordination and loss of good judgment. Speech can be slurred; balance, vision, reaction time and hearing impaired. Euphoria. 0.13-0.15 Gross motor impairment and lack of physical control. Blurred vision and major loss of balance. Euphoria is reduced and dysphoria is beginning to appear 0.16-0.20 Dysphoria (anxiety, restlessness predominates; nausea can appear. The drinker has the appearance of a “sloppy drunk” 0.25 Needs assistance in walking; total mental confusion. Dysphoria with nausea and some vomiting 0.30 Loss of consciousness 0.40 Onset of coma, possible death caused by respiratory arrest is 15 GUIDELINES FOR ALCOHOL DRINKING  Moderate Alcohol Consumption:  Women: ≤ 1 drink/day  Men: ≤ 2 drinks/day 2 drinks x 7 days = 14 drinks/week for men a This Photo by Unknown author is licensed under CC BY-NC-ND. e 16 CDC. Frequently Asked Questions. 2016 ADVERSE EFFECTS OF CHRONIC ALCOHOL CONSUMPTION  Drinking alcohol increases risk of cancer o Mouth o Esophagus o Pharynx o Larynx o Liver o Breast  Fetal alcohol spectrum disorder (FASD)  Wernicke-Korsakoff syndrome o “Alcohol related dementia”  Alcohol Related Brain Damage (ARBD) 17 NIAAA, 2018 Thompson AD, 2012 DSM-5: ALCOHOL USE DISORDER Problematic pattern of use that causes significant distress or harm, with at least two of the following over 12 months Larger amounts or longer duration than was intended Unsuccessful efforts to cut down or control use Large amounts of time spent obtaining, using or recovering from alcohol Cravings Continued use despite adverse consequences to socialinteraction kidswife y sobsfights Enjoyable activities given up or reduced Use in physical or hazardous situations 055 Use despite knowledge of condition that is exacerbated by alcohol Tolerance Withdrawal symptoms or alcohol or benzodiazepines (BZD) used to avoid withdrawal symptoms DSM-5, 2013 19 KNOWLEDGE CHECK 0.08 aLegat  KM is 22 yo M college student and was brought to emergency department by his friends. He was found to have a BAC of 0.30, when you go to visit him, how would you expect to find him? Blackout 21 ALCOHOL AND NEUROTRANSMITTERS  Under normal conditions, there is a balance between the inhibitory and excitatory neurotransmitters (NT)  Alcohol affects brain function by interacting with multiple NT  Alcohol disrupts the balance between excitatory and inhibitory NT Inhibitory • GABA • Adenosine • Glycine Excitatory • Aspartate • Glutamate se Alcohol Health and Research World. Alcohol and Neurotransmitter Interactions. line edalliblium NORMAL CONDITION SHORT-TERM ALCOHOL -reduced anxiety -change in mood, drowsiness, alterations in memory Alcohol Health and Research World. Alcohol and Neurotransmitter Interactions me LONG-TERM ALCOHOL ow jxb -Prolonged exposure and at high doses: upregulation of NMDA receptors and down regulation of GABA-A first Bet ALCOHOL WITHDRAWAL When alcohol is stopped abruptly imbalance between excitatory & inhibitory signals withdrawal sx 23 PATIENT ASSESSMENT  Initial evaluation should include: • Current and past use of tobacco and alcohol • Misuse of other substances including other substance use disorders, OTC, supplements so • Quantitative behavioral measure to detect presence of alcohol misuse and severity e.g CAGE • Assess psychiatric disorders and other medical disorders to influence selection of pharmacotherapy • Use of physiological biomarkers Discussion of Risk to Self Initial Goal Discussion of Risk to Others APA guideline, 2018 tool Scrying mpg CAGE QUESTIONNAIRE down cutting Annoyed guilty eyeopenersdrinfirstthirgintremoring 1. Have you ever felt you should Cut down your drinking? 2. Have people Annoyed you by criticizing your drinking? 3. Have you ever felt bad or Guilty about your drinking? 4. Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener) the29 atleast to yes say A total score of 2 or greater is considered clinically significant. 25 Noneedto PHYSIOLOGICAL BIOMARKERS memorisejust knowit Direct Biomarkers Serum ethanol level o Normalizes within hours of alcohol cessation o For detection of acute use Hair/urine ethyl glucuronidase (EtG) o Can be detected up to 2-5 days after last drink o For detection of acute use Phosphatidylethanol (Peth) o Requires at least 2-4 standard drinks/day x several weeks o Remains elevated for 2-3 wks after cessation of drinking Indirect Biomarkers Carbohydrate-deficient transferrin (%CDT)—detects only heavy drinkers in the weeks prior to testing Gamma-glutamyl transferase (GGT)early indicator of liver disease es Alanine transaminase (ALT), aspartate transaminase (AST) Tifhighitingut moonliverproblan Mean corpuscular volume (MCV) ----Increased w/ heavy alcohol use and 26 remain increased for 3-4 mo after abstaining alcohol APA guideline, 2018 ALCOHOL WITHDRAWAL SYMPTOMS Confusion Insomnia Tremor Seizure Autonomic hyperactivity Hallucination N/V Anxiety/agitation Given that alcohol withdrawal is itself a diagnostic criterion for AUD, patients presenting with alcohol withdrawal sx almost certainly also have an AUD. AAFP guideline, 2004, ASAM guideline, 2020 DSM-V CRITERIA OF ALCOHOL WITHDRAWAL 048 all 29 DSM-5 CRITERIA FOR ALCOHOL WITHDRAWAL DELIRIUM 30 If delirium is the predominant sx, the diagnosis should be “substance withdrawal ALCOHOL WITHDRAWAL DIAGNOSIS/DIFFERENTIAL DIAGNOSIS  It is essential to rule out other possible explanations for the constellation of signs and symptoms of withdrawals  Some medical conditions including hypoglycemia and diabetic ketoacidosis both can mimic alcohol withdrawal  S/sx of sedative/hypnotic, or anxiolytic withdrawal are similar to those of alcohol withdrawal, underscoring the importance of assessing for recent alcohol and other substance use.  For pt appearing to have alcohol withdrawal sx, assess for  For possible concomitant withdrawal from other substances e.g. BZD  If recent alcohol use and cessation/ reduction suggests possible withdrawal, but the patients is not exhibiting any s/sx of withdrawal, clinicians should consider whether the patient is taking any medications that can mask these symptoms, such beta-blockers  Clinicians should seek information about the time elapsed since the patient’s cessation of (or reduction in) alcohol use. The timeline of symptom onset and severity helps determine the risk window for developing severe or complicated withdrawal. 31 TIME OF APPEARANCE IF ALCOHOL WITHDRAWAL SYMPTOMS Symptoms Time after cessation (hours) Minor sx: insomnia, mild anxiety, tremors, 6-12 diaphoresis, headache, GI upset, math palpitations Hallucinations 12-24 Withdrawal seizures: generalized-tonic clonic 24-48 Alcohol withdrawal delirium (delirium 28-72 (up to 5 days) tremens): hallucinations, disorientation, tachycardia, hypertension, fever, agitation, diaphoresis Distinguish between hallucinosis and alcohol withdrawal delirium when making a diagnosis, although this may not always be possible during the early stages of withdrawal. If hallucinations persist beyond 72 hours of onset, the more likely diagnosis is alcohol-related psychotic disorder 32 ASAAM guideline, 2020, AAFP guideline, 2004 TIMELINE OF ALCOHOL WITHDRAWAL Following an alcohol withdrawal seizure, a patient is at increased risk for another seizure and progression to alcohol withdrawal delirium 33 GOALS OF TREATMENT Provide a safe withdrawal Enable patients to become “drugfree” Treatment of alcohol dependence & other drugs 36 Kasser C, 2004 KNOWLEDGE CHECK  Which of the following are indirect biomarkers alcohol consumption. Select all that apply A. GGT B. EtG C. %CDT D. Blood alcohol concentration 37 RISK FACTORS FOR SEVERE OR COMPLICATED WITHDRAWAL  Recommendation: Assess for the factors associated with increased patient risk for complicated withdrawal or complications of withdrawal:  History of alcohol withdrawal delirium or alcohol withdrawal seizure  Numerous prior withdrawal episodes in the patient’s lifetime  Comorbid medical or surgical illness (especially traumatic brain injury)  Increased age (>65)  Long duration of heavy and regular alcohol consumption  Seizure(s) during the current withdrawal episode  Marked autonomic hyperactivity on presentation  Physiological dependence on GABAergic agents such as benzodiazepines or barbiturates  Concomitant use of other addictive substances  Positive blood alcohol concentration in the presence of signs and symptoms of withdrawal  Signs or symptoms of a co-occurring psychiatric disorder that are active with moderate level of severity 38 CLINICAL INSTITUTE WITHDRAWAL ASSESSMENT FOR ALCOHOL-REVISED (CIWA-AR)  It evaluates In general, clinicians may consider patients at risk of severe or complicated withdrawal if they are experiencing at least moderate alcohol withdrawal on presentation (e.g., CIWA-Ar score 10). o N/V o Tremors o Sweats o Anxiety o Agitation o Tactile disturbances o Auditory disturbances o Visual disturbances o Headache o Orientation to time/place/people  Max score= 67  Mild < 8; moderate 9-15; severe >16  Monitor CIWA-Ar q 4-8 hrs until the score < 8-10 points for 24 hrs Alcohol withdrawal severity assessment scales [CIWA-Ar]) should not be used as a diagnostic tool for alcohol withdrawal diagnosis because scores can be influenced by conditions other than alcohol withdrawal 39 AAFP guideline, 2004 APPROACH TO MANAGEMENT OF ALCOHOL WITHDRAWAL  Level of care determination should be based on a patient’s current s/sx, level of risk for developing severe or complicated withdrawal or complications of withdrawal;.  Alcohol withdrawal can typically be safely managed in an ambulatory setting for those patients with limited jewsor mitigated risk factors.   Patients with low levels of psychosocial support or an unsafe environment may benefit from a more intensive level of care than is otherwise indicated. Pharmacotherapy is aimed at:   Reversing the GABA-A deficiency  BZDs  Carbamazepine  Divalproex sodium Decreasing the over activity of the excitatory glutamate (adjunct)   Clonidine (alpha2-adrenergic agonists ) Do both actions (adjunct)  Phenobarbital e.g. Phenytoin 40 MANAGEMENT OF ALCOHOL WITHDRAWAL Balance  Pharmacological wi seized Helps deletiam (including pregnant pts) as o 1st line: BZD o Alternative or adjunct: Carbamazepine, Gabapentin (as monotherapy in mild cases or as adjunct in moderate-severe cases). Also they reduce cravings o Others: Phenytoin may also be used if CI to BZD may be used o Adjunct: Haloperidol, beta-blockers, clonidine, Depakote hallooing G not lontraindication  Monitor: vital signs  Other (banana bag)—Thiamine, folate and multivitamin (makes it yellow) o IV fluids (severe cases) o Correction of electrolytes Br   Hypomagnesemia magnesium sulphate  Multivitamins (IV)  Folic acid 400-1000 mcg f  m onotherapy Thiamine 100 mg/d IV/PO PO 3-5 days  Deficiency: Wernicke's Encephalopathy (WE)  If WE is suspected, give IV thiamine Nutrition  Hydration: consumption of non-caffeinated drinks (ambulatory setting) due to volume depletion  Daily PO multivitamins and thiamine 41 ASAAM guideline, 2020 AAFP guideline, 2004 ADJUNCT MEDICATIONS narrow Haloperidol (Haldol) For agitation and hallucinations Beta Blockers Consider in patients with coronary artery disease Improves autonomic sx (HTN, tachycardia) E Caution: can lower seizure threshold Clonidine (Catapress) Atenolol (Tenormin) •In combo w/ Serax improves vital signs and reducing alcohol cravings more effectively than use of Serax alone Improves autonomic symptoms of alcohol withdrawal (e.g. HTN, tachycardia) tapatic Phenytoin (Dilantin) indet Does NOT treat withdrawal seizures Appropriate for patients with underlying seizure disorder or CI to BZD 42 AAFP guideline, 2004 WERNICKE-KORSAKOFF SYNDROME Anatfogivety Wernicke Encephalopathy (WE)  Rare acute, reversible neurological condition (confusional state) My  Life threatening caused by thiamine deficiency (vitamin B1) Triad Symptoms ratesisff Ophthalmoplegia with nystagmus (hallmark sign)  else   1. lackofiordination 2. Gait ataxia 3. Acute mental confusion (may progress to coma/death) 4. Possibly delirium Prevention o Discontinuing excess alcohol consumption o Thiamine Korsakoff Syndrome/psychosis  Result of untreated WE. It is irreversible.  Results from permanent damage to brain  Is preventable  Consequence of at least one episode of WE (complication of WE)  Neuropsychiatric disorder o Memory disturbances/dementia: anterograde and retrograde memory o Confabulation o Hallucinations o Gait abnormalities n'makeupstories twist Management o High dose thiamine (IV) 200 mg TID 43 EFNS guideline, 2010 Thomson AD, et al, 2012 to need No knowthe BENZODIAZEPINES doses seizures and in alcohol withdrawal  Prevents and treats delirium and used for primary and secondary prevention of patients  Higher numbers of previous alcohol withdrawal episodes is associated with decreased responsiveness to BZDs. Failure to respond may also be due to withdrawal from another GABAergic agent such as gabapentin. In these cases, switching to an alternative medication should be considered. Front-load: q 1004in 1-2 hrs dose typically x 3 doses if CIWA >19) Chrlordiazepoxide 100 mg q 1-2 hrs until pt is sedated/CIWA<10 Diazepam 10-20 mg q 1-2 hrs until pt is sedated/or CIWA<10 A front loading regimen is recommended for patients at high risk of severe withdrawal syndrome, positive blood alcohol, severe CAD, acute medical/psychiatric illness Fixed schedule: BZD q 6 hrs Symptom-triggered (Score >8) I pg Chlordiazepoxide (Librium) 50 mg x 4 doses, then 25 mg x 8 doses Diazepam (Valium) 10 mg x 4 doses, then 5 mg x 8 doses Lorazepam (Ativan) 2 mg x 4 doses, then 1 mg x 8 doses Chlordiazepoxide (Librium) 50-100 mg Oxazepam (Serax) 30 mg x 4 doses, then 15 mg x 8 doses Oxazepam (Serax) 15-30 mg Diazepam (Valium) 10-20 mg Lorazepam (Ativan) 2-4 mg For delirium, use IV BZD 44 *Lorazepam and oxazepam (Serax) are preferred in patients with liver dysfunction and/or elderly AAFP guideline, 2004 BZD COMPARISON CHART BZD Onset Half-Life Active Metabolite Chlordiazepoxide (Librium) Intermediate Long Yes Diazepam (Valium) Quick (Immediate) Long Yes Clonopin (Klonopin) Intermediate/slow Long No Intermediate Intermediate No Short/Intermediate No Lorazepam (Ativan) Oxazepam (Serax) It apparIntermediate/slow Alprazolam (Xanax) Intermediate Short No Triazolam (Halcion) Quick (Immediate) Very short No Temazepam (Restoril) Intermediate/slow Intermediate No If liver impairment status is unknow (e.g. awaiting labs), use BZD that are less metabolized by liver (Lorazepam, oxazepam) 45 SUMMARY 1. CIWA-Ar is a validated 10-item assessment to quantify severity of alcohol withdrawal 2. Long-acting benzodiazepines are used first line for treatment of alcohol withdrawal symptoms and to prevent/treat seizures and delirium 3. Symptom-triggered regimen has shown to result in administration of less medications and to require a shorter duration of treatment 4. Wernicke-Korsakoff Syndrome is caused as a result of thiamine deficiency 46 CASE  Identification Data: MT is a 40 yo white male admitted for alcohol detox  Chief Complaint: “I have been drinking 20 years, I want to stop drinking. I have been running into problems”  History of Present Illness: Patient states that he has been drinking since he was 18. He has been a daily drinker for the past 20 years. He drinks about 12 beer per day. He never had any treatments. This is his first detox. The patient reports recently having blackouts and drinking more since the death of his brother in July of this year. The patient has a long history of alcoholism. He started drinking alcohol when he entered college and after first year of college he had to drop out because of his grades. He smoked marijuana since his children were born. He is also dealing with heroin 48 addiction and he is being treated for that. CASE  Past Psychiatric History: The patient states that he has been more anxious and depressed but denies suicidal ideation. He is being treated for depression. He also reports not being adherent to his medications.  Past Medical History: He has been diagnosed with hypertension, which he is using medications for.  Family History: He reports family history of alcoholism. No mental health history.  Social History: He was brought up by a single mother after his father divorced his mother when he was 5. He is also divorced from wife and has two children, a son who is 15 and a daughter who is 21. He is currently living in Willingboro with his daughter. Both daughter and boyfriend drink a lot. Patient is working at a factory. He has been in that factory since he dropped out of college. CASE  Review of Systems: Residual withdrawal symptoms  Physical Exam: Normal  Weight: 180 lb; Ht: 6’2  Labs:  Serum creatinine: 3.8 mg/dl  AST: 60 U/L [10-40 U/L)  ALT: 75 U/L [7-56 U/L]  CBC: Within normal limits 50 CASE  Current Medications:  Sertraline (Zoloft) 100 mg PO QD  Metoprolol Succinate (Toprol XL) 25 mg tablet PO QD  Buprenorphine/Naloxone (Suboxone) 8mg-2mg SL QD  Diagnosis and Impression: Alcohol & heroin dependence, withdrawal symptoms, major depressive disorder. Co-morbidities include hypertension and renal dysfunction 51 PHARMACOLOGICAL TREATMENT FOR ALCOHOL-DEPENDENT PATIENTS Naltrexone if Acamprosate Disulfiram • PO= Depade®, ReVia®; XR IM Injection= Vivitrol® er or maintain their abstinence. • Appropriate for patients who want to cut down • The overall benefit seems to be better if the patient can maintain abstinence for at least 4 days • Campral® • May decrease alcohol craving in abstinent individuals • Antabuse® • Inhibits alcohol dehydrogenase (ADH) Topiramate • Topomax ® • Off-label Gabapentin • Neurontin ® • Off-label Carbamazepine • Tegretol ® • Off label Pharmacological treatment of Patients with alcohol use disorder. APA guideline, 2018 movintrance maintencewithdrew montane withered 52 NALTREXONE Mechanism of Action opioid dependence indicator ifopioduse is contra Ptwillhavewithdrawalsymptoms • Opioid antagonist with the highest affinity for the mu-receptor; Decreases GABA and reduces DA release Efficacy • • • • Reduces DA release Reduces euphoric effect Reduces heavy drinking Helps maintain abstinence Safety • Hepatotoxicity, liver enzyme elevation, depression and suicidality, injection site reaction (Vivitrol®) • Caution in hepatitis C and hepatic failure; CI in current opioid use Doses • Oral: 50 mg once daily • IM: 380 mg once every 4 weeks 53 APA guideline, 2018 NALTREXONE INJECTION  Indication:  Treats alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with Vivitrol®  Prevents opioid relapse after opioid detox  Route: IM  Strength: 380 mg/vial  REMS  May be more effective than the oral version  Dose and Administration:  380 mg IM in the gluteal muscle every 4 weeks (alternating buttocks for each subsequent injection)  Prior to initiation, patient must be opioid-free (including tramadol) for at least 7-14 days to avoid precipitation of opioid withdrawal symptoms  Must be administered by a healthcare provider  No data on re-initiation of Vivitrol® after a period of discontinuation Vivitrol [package insert]. Waltham, MA: Alkermes Inc; 2015 NALTREXONE IM: REMS PROGRAM  Goal of the REMS is to inform patients and healthcare providers about severe injection site reactions  Advise patients about: o Risk of opioid overdose o Severe injection reaction o Risk of precipitated opioid withdrawal o Risk of hepatotoxicity including hepatitis o Possibility that patients may not feel the therapeutic effects of opioid-containing medicines Food and Drug Administration. Vivitrol (naltrexone) REMS. OPIOIDS USE AND NALTREXONE  Precipitation of opioid withdrawal symptoms  Opioid-dependent and opioid using patients, including those being treated for alcohol dependence, should be opioid-free before initiation of Naltrexone (IM) treatment for a minimum of 7-14 days  Challenge test might be helpful: No systematically collected data on how to switch from oral to IM naltrexone I T  Vulnerability to opioid overdose:  Naltrexone will competitively bind to opioid receptors and reversibly block effects of exogenous opioids  I but overcoming full naltrexone blockade by This makes the blockade potentially surmountable, administering opioids  Attempts to overcome blockade may also lead to fatal overdose Vivitrol [package insert]. Waltham, MA: Alkermes Inc; 2015 PAIN MANAGEMENT 1. Patients with substance abuse problem have lower pain threshold 2. Naltrexone is pure opioid µ receptor antagonist blocks effects opioid analgesics in case of emergency pain management  Increased resistance to opioids should be expected for pain management during surgeries  However, increased sensitivity is also a possibility Vickers AP, et al. 2006 PAIN MANAGEMENT OPTIONS  Non-opioid:  High dose NSAIDS: IBU 2400mg/day  IV acetaminophen  Ketamine  Tramadol???  Local anesthesia:  E.g Epidurals Vickers AP, et al. 2006 ACAMPROSATE Mechanism of Action • Modulates the balance between excitatory (glutamate) by reducing it’s activity and supporting function of inhibitory (GABA) neurotransmission in the brain • Promotes abstinence by balancing GABA and glutamate system Bso Efficacy • • • • Less likely to return to drinking after attaining abstinence Reduction in # of drinking days; Mixed data on # of heavy drinking days Effects begin in couple days A period of abstinence is recommended prior to initiation Safety •Must be renally dose adjusted; avoid in CrCl ≤ 30 ml/min •Can be used in patients with liver impairment •No DDIs APA guideline, 2018 61 DISULFIRAM Mechanism of Action • Inhibits aldehyde dehydrogenase (ALDH) Ethanol orAcetaldehyde Disulfiram reaction: flushing, Acetate throbbing in head and neck, nausea, vomiting, tachycardia, resp depression, cardiovascular collapse, arrhythmia, death Efficacy rag evidence is limited • Alcohol deterrent; • More effective with monitored administration Safety • Several safety considerations and significant toxicity risk o Hepatotoxicity, caution in patients w/ hx of seizures o Drug-drug interactions o Avoid in cardiovascular disease 62 APA guideline, 2018 Clinical Pearls Naltrexone oral Naltrexone injection Acamprosate Disulfiram Effective at decreasing drinking, and craving and increasing abstinence Same as oral Patients with goal of abstinence Patients with goal of abstinence and monitored administration Better for adherence Naloxone challenge test Motivated patients Contraindicati ons Opioids dependence with use within past 7 days Acute hepatotoxicity (Canadian labelling) Opioids dependence with use within past 7-14 days CrCl < 30 ml/min Alcohol containing products within 14 days of use. Avoid alcohol >12 hrs prior to admin. DDI: Flagyl, anticoagulants Severe myocardial disease Individuals with psychotic disorder Baseline Evaluation Opioid-free LFTs Opioid-free LFTs CrCl Abstinence x 4 days prior to admission Alcohol free >24 hrs LFTs EKG Dose Initiation 25 mg PO on first day, then increase to 50 mg PO daily 380 mg IM monthly 666 mg PO TID; 333 mg PO TID if CrCl 30-50 250 mg PO daily Grabaday Alternate: 50 mg PO weekdays (100 mg of Saturdays) OR 100 mg orally every other day; OR 150 mg orally every third day ADR N/V, Headache Dizziness Somnolence Same as oral + injection site reaction Diarrhea Insomnia Anxiety 63 taste Metallic or garlic like after Psychosis, delirium Iiver failure KNOWLEDGE CHECK severe  MT had a CIWA-Ar score of 16. Which of the following treatment would be first line for MT’s alcohol withdrawal Bento long symptoms? Firstline A. Gabapentin 600 mg TID B. Lorazepam (Ativan) 2 mg q 6 hrs x 4 doses, then 1 mg q 6hrs x 8 doses pot C.asAlprazolam (Xanax) 2 mg q6 hrs, x 4 doses, then 1 mg q 6hrs x 8 doses LeslieD. Flumazenil 0.3 mg IV Entogenist 65 KNOWLEDGE CHECK first Not spithepato ptheroinuser KII Ag 180lb ag.gg jiaidEox 81  MT has agreed to be on a medication for long term treatment of his alcohol dependence. Which medication is the best choice? 1140 aggildealogt A- Naltrexone PO Songdaily B- Naltrexone IMson380aryawert C- Acamprosate Cook30 A D- Disulfiram ad era 7.21sort 114040118181 71 381 299 SE BAD 66 KNOWLEDGE CHECK  The psychiatrist decides to put MT on Naltrexone. When can Naltrexone be started? A- Right away B- Wait 5 days after Suboxone detox, then give Naltrexone IM (Vivitrol®) C- Wait 7 days after Suboxone detox, then give PO Naltrexone for 1 day, then give Naltrexone IM (Vivitrol®) D- Wait 10-14 days after Suboxone detox, then give PO Naltrexone for 3-4 days, then give Naltrexone IM (Vivitrol®) 67 offleble TOPIRAMATE Alcoholdependence  Anticonvulsant and for prevention of migraine  Associated with abstinence and significant reductions in IT o % of heavy drinking o % drinking days o Number of drinks per drinking day o Cravings  Off-label doses: 100-150 mg BID (titrate slowly over 8 weeks)—Divided in 2 doses  Side effects:  o Common: Weight loss, sedation, cognitive dysfunction (e.g effects on short term memory), paresthesia, GI, taste abnormalities o Less common: nephrolithiasis, acute angle-closure glaucoma Caution in renal impairment, elderly (risk of falls), DDI with oral contraceptives at high doses, pregnancy category D 69 APA guideline, 2018 GABAPENTIN  Anticonvulsant  GABA analogue  Associated with abstinence and reductions in o Drinking quantity and frequency o Mild withdrawal o Cravings o Insomnia  Off-label dose: 300-1200 mg/ TID  Side effects: o  Common: Sedation, dizziness, weight gain, fatigue, worsen depression Caution: renal impairment, misuse/abuse of gabapentin (some states schedule V)euphoric/sedative properties 70 APA guideline, 2018 CARBAMAZEPINE (TEGRETOL ®)  Anticonvulsant  Reverses GABA deficiency  Not first line  May be appropriate in pts with concurrent seizure disorder or mood disorder  Reduces alcohol cravings  Dose: Initiate at 200 mg BID, maintain at 600-800 mg/day  ADR: dizziness, nausea, ataxia, agranulocytosis  CYP3A4 inducer 71 SUMMARY OF MEDICATIONS  Reduce drinking days and promote abstinence  Naltrexone  Acamprosate  Gabapentin  Topiramate  Promote abstinence only  Disulfiram 72 DURATION OF TREATMENT Patient preference  No optimal duration of treatment established  Factors affecting decision Tolerability Severity of alcohol use disorder Clinical response History of relapse Potential consequence of relapse 75 APA guideline, 2018 SELECTION OF PHARMACOTHERAPY Naltrexone or acamprosate is recommended to be offered in moderatesevere cases in those who (1B) • Have a goal of reducing alcohol consumption or achieving abstinence • Prefer pharmacotherapy or have not responded to non-pharmacological treatments alone Disulfiram is suggested to be offered to patients with moderate-severe AUD who (2C) • Have a goal of achieving abstinence • Prefer disulfiram or are intolerant to naltrexone or acamprosate • Are capable of understanding the risks of alcohol consumption while taking disulfiram Topiramate or gabapentin is suggested to be offered to patients with moderate to severe alcohol use disorder who (2C) • Have a goal of reducing alcohol consumption or achieving abstinence • Prefer topiramate or gabapentin or are intolerant to or have not responded to naltrexone and acamprosate APA guideline, 2018 RECOMMENDATIONS AGAINST USE OF SPECIFIC MEDICATIONS not Bero maintenance  It is recommended AGAINST the use of: Benzodiazepines for alcohol use disorder unless it is used for treatment of alcohol withdrawal therapy Pharmacological treatment in pregnant/breast feeding women Acamprosate as first line in patients with mild-moderate renal impairment Naltrexone in patients with acute hepatitis or hepatic failure Naltrexone in individuals who use or may to use opioids APA guideline, 2018 BENZODIAZEPINE DEPENDENCE 78 highbeddictive BZD USE/MISUSE  Women are prescribed BZD twice as much as men National Drug Overdose Deaths Involving BZD, by Opioid Involvement Among all Ages (1999-2017)  Individuals prescribed opioids are more likely to be prescribed BZD  Abuse Patterns 1. Deliberate or recreational abuse with the intention of getting high 2. Unintentional abuse, starting with legitimate prescriptions  Young adults (18-35 yo) comprise the largest portion of abusers 79 Agarwal SD, ett al, 2019 Brett J, et al, 2015 National Institute on Drug Abuse, 2018 BZD INTOXICATION  Intoxicated patient may be in acute distress in overdoses or when BZD is combined with alcohol  Intoxicated patients may appear with o Slurred speech o Poor coordination o Blood shot eyes o Swaying o With or without odor of alcohol  Flumazenil, a GABA receptor antagonist is, used for BZD overdoses 80 Dipiro JT. et al, 2016 BENZODIAZEPINE WITHDRAWAL SYMPTOMS Anxiety related symptoms Perceptual distortions • Anxiety, panic attacks, hyperventilation, tremor • Sleep disturbances, muscle spasms • Visual disturbances, sweating • Altered mood • Abnormal body sensations Major events Other • seizures • Hallucinations • Flu-like symptoms • N/V • Impaired memory and concentration CIWA-B (20-item) can be used to assess BZD assessment 81 SA Health taperday Benz acting ten long aan BZD WITHDRAWAL MANAGEMENT  Withdrawals are managed by converting to a long acting BZD and gradually decreasing the total daily dose o Ex. Convert to diazepam (Valium) equivalent dose (max 40 mg diazepam) Diazepam Equivalency 82 Clinical guidelines for withdrawal management and treatment of drug dependence in closed settings, 2009 TAPERING DIAZEPAM Low-dose BZD reducing schedule High-dose BZD reducing schedule Note: Generally, one week between each dose reductions Gradual taper of benzodiazepines should occur over 4–8 weeks and sometimes longer depending on the duration of use 83 Clinical guidelines for withdrawal management and treatment of drug dependence in closed settings, 2009 TAPERING DIAZEPAM • Gradual taper of benzodiazepines should occur over 4–8 weeks and sometimes longer depending on the duration of use • Reduce the daily dose 10%–25% every 2 weeks to decrease the risk of severe withdrawal reactions and seizures • Minor abstinence symptoms (ie, anxiety, insomnia, irritability, sensitivity to light and sound, and muscle spasms) can remain for several weeks after the acute phase of withdrawal 84 SUMMARY • BZD effects are exacerbated with CNS depressants • BZD withdrawal symptoms include rebound insomnia, agitation, hallucinations and seizures • BZD withdrawal is managed by long-acting BZDs 85