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1 Please review the following slides prior to class Information from these slides will be used to answer patient cases. Come prepared!

2 Alcohol and Opiate Dependence Reference Slides

3 Substances of Abuse A to Z

4 Cannabinoids } Active Ingredient } Tetrahydrocannabinol (THC) } Clinical Effects } Anxiolysis } Sensory Intensification } Feelings of well- being

5 Cannabinoids: Marijuana #1 illicit substance abused in US PO or smoked Heavy users Withdrawal Restlessness, irritability, insomnia Amotivational syndrome Psychological addiction

6 Cannabinoids: Synthetic } Cannabinoid receptor agonist } Pseudonyms } K2 } Spice } Recently classified as Schedule I } Adverse Effects: agitation, anxiety, nausea, vomiting, tachycardia, HTN, tremor, seizures, hallucinations, paranoid behavior

7 Cocaine Administration Intranasal Intravenous Smoked Freebase Cocaine Coca Plant Cocaine Hydrochloride Crack Cocaine

8 Cocaine } Clinical Effects } Euphoria } Increase energy } Binge use followed by cocaine crash } Anhedonia } Depression } Suicidal Ideation

9 Dextromethorphan DXM, DM, Triple Cs, Skittles, Robotrip } Synthetic opioid & NMDA antagonist Plateau Dose (mg) Effects 1 st Mild stimulation 2 nd Euphoria and hallucinations 3 rd Distorted visual perceptions, loss of motor coordination 4 th Dissociative sedation

10 Dextromethorphan DXM, DM, Triple Cs, Skittles, Robotrip } Psychiatric AE } Suicidal ideation } Psychosis } Additional AEs } Dependent on other ingredients } 2D6 Substrate } Watch for 2D6 Inhibitors } Fluoxetine } Paroxetine } Serotonin Syndrome } Case Reports Miller, SC. Addiction Biology 2005; 10:

11 Hallucinogens } LSD, PCP, peyote, mescaline, psilocybin mushrooms, and "Ecstasy" (MDMA)

12 Mephedrone / MDPV (Methylenedioxypyrovalerone) Psuedonyms Ivory wave Bliss White lightening Hurricane charlie Meow- meow Marketed as bath salts and plant food Emerg Med J doi: /emj.2010

13 Mephedrone / MDPV (Methylenedioxypyrovalerone) Emerg Med J doi: /emj.2010

14 Mephedrone Easily Accessible Ingested orally, inhaled, or injected Worst outcomes seen with snorting or injecting

15 Methamphetamine ice, glass, speed, chalk, crystal } Sources } Superlabs } Small, home- based operations } Basis for pseudoephedrine restrictions PO Inhaled Multimodal administration Intranasal IV

16 Methamphetamine } Long- term effects } Meth Mouth } Xerostoma, bruxism, poor hygiene } Weight loss } Psychosis

17 Inhalants Nitrous oxide Amyl nitrite Cleaning fluids Gasoline Spray paint Other aerosol sprays Glue

18 Inhalants } Clinical Effects } Similar to alcohol } Dissociation } Instant euphoria } Mode of administration } Sniffed } Huffed } Bagged } Adverse Effects } Huffer s rash } Sudden sniffing death syndrome } Cognitive impairment

19 Treatment for Alcohol Withdrawal

20 Treatment Regimens for Alcohol Withdrawal: Benzodiazepines (BZDs) } First- line } Replace alcohol s inhibitory effect on GABA } No consensus on best choice: Long- acting Chlordiaz- epoxide (Librium ) Short- acting Lorazepam (Ativan ) Diazepam (Valium ) J Neurol Neurosurg Psychiatr 2008; 79: Lancet 2006; 368:

21 Treatment Regimens for AWS: Benzodiazepines (BZDs) Long- Acting } Smoother course of withdrawal } Fewer rebound symptoms } Front- load, fixed schedule } Excessive sedation in some populations } Liver disease, elderly Short- acting } Fixed schedule or symptom- triggered } May lessen total BZD administration Oxazepam Temazepam Lorazepam J Neurol Neurosurg Psychiatr 2008; 79:

22 Benzodiazepine Treatment Regimens Fixed- schedule Front- loading Symptom- triggered

23 Fixed- Schedule } BZD provided regularly at fixed dosing intervals } Gold standard } Indicated if history of complicated withdrawal } May be preferable if pregnant Example: Day 1 Day 2 Day 3 Day 4 Lorazepam 2mg PO q8h Lorazepam 1mg PO q8h Lorazepam 1mg PO q12h Lorazepam 1mg PO qday x1

24 Front- Loading } High dose, long- acting BZD (diazepam) } Treat early signs/symptoms } Long- acting parent + metabolites eliminate need for future doses (i.e., self- taper) } Intense monitoring and medication administration limited to early symptomatic period Example: Diazepam 20mg PO q2h until symptom resolution No further doses

25 Symptom Triggered } Medicate only when symptoms present } Assessed via structured withdrawal assessment scale } Reduced amount of medication required } Less sedation } Decreased duration of treatment Arch Intern Med 2002; 162:

26 CIWA Protocol: Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA- Ar) } Grades severity of symptoms of alcohol withdrawal Nausea Diaphoresis Agitation Headache Anxiety Tremor Sensory disturbances Orientation Max Score = 67 J Neurol Neurosurg Psychiatr 2008; 79: Lancet 2006; 368:

27 CIWA Protocol: Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA- Ar) CIWA>9 Give BZD Repeat every hour until CIWA<10 Continue BZD dosing until CIWA<9 Repeat every 8 hours and discontinue protocol when CIWA<6 Must have this score on four consecutive occasions J Neurol Neurosurg Psychiatr 2008; 79:

28 DSM- IV- TR Criteria: AWS } 2 of the following after cessation/reduction in alcohol use that has been heavy/prolonged: Autonomic hyperactivity Hand tremor Insomnia Nausea/ Vomiting Hallucinations Psychomotor agitation Anxiety Tonic- clonic seizures J Neurol Neurosurg Psychiatr 2008; 79:

29 Alcohol Withdrawal Syndrome Stage 2: Alcohol hallucinosis Stage 3: Seizures Stage 1: Mild- moderate withdrawal symptoms Treatment: BZDs Stage 4: Delirium tremens

30 Stage 1: Mild- Moderate Symptoms } Symptoms: } Autonomic instability } GI disturbance } Tachycardia } Hypertension } Diaphoresis } Tremulousness } Anxiety } Hyperreflexia } Insomnia } 6 8 hours after last drink CNS Spectrums 2000; 5:

31 Stage 2: Alcohol Hallucinosis } Hallucinations } Auditory } Visual } Tactile } Antipsychotics ineffective } 24 hours

32 Stage 3: Seizures } Tonic- clonic Risk Factors Electrolyte disturbances Hypoglycemia CNS infection Occult traumatic intracranial hemorrhage Illicit drug use Previous seizure } 7 48 hours J Neurol Neurosurg Psychiatr 2008; 79:

33 Stage 4: Delirium Tremens } Symptoms } Confusion } Hallucinations } Agitation } Tachycardia } Mydriasis } Fever } 3 5 days J Neurol Neurosurg Psychiatr 2008; 79: Lancet 2006; 368:

34 } Take Home Points: } Antipsychotics ineffective } DTs can be fatal Alcohol Withdrawal Syndrome Complications See background reading Know stages of alcohol withdrawal!

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