Intoxication, Dependence, Withdrawal 2010

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Intoxication, Dependence, Withdrawal Richard Wahl, M.D.

University of Arizona Dept. of PediatricsNovember 2, 2010

INTOXICATION (Identification)

1. Endogenous Receptors for Drugs of Abuse

Cocaine/Amphetamines : Dopamine reuptake transporter

Ethanol: GABA receptor stimulation, NMDA(N-methyl-D-aspartic acid) glutamatereceptor inhibition.

LSD & other Hallucinogens : Serotonin (5-HT2) receptor partial stimulation.

Marijuana (THC): CB1 cannabinoid receptor stimulation

Nicotine : Nicotinic acetylcholine receptor stimulation

Opiates : Mu () opiate receptor stimulation

Phencyclidine (PCP) and Ketamine: NMDA glutamate receptor blockade

2. UMC (Tucson) Urine Drugs of Abuse Screen EMIT (Enzyme Multiplied Immunoassay Technique) Antibody screen for specific

drugs or their metabolites.Amphetamine: Amphetamine, methamphetamine

Cocaine: cocaine metabolitesOpiates: morphine assay, picks up codeine, heroin

Excludes opioids: oxycodone, hydrocodone, fentanyl, propoxypene,meperidine, methadone.

Benzodiazepine: nordiazepine metabolites; not Flunitrazepam (Rohypnol).Barbituates: Secobarbital (Seconol), phenobarbital

Phencyclidine (PCP): Also detects high levels of Dextromethorphan (DXM)If positive, lab will run second assay to distinguish PCP from DXM.

Cannibanoids: THC is lipid-soluble, may remain in fat stores 4-6 weeks

3. PCH Urine Drug of Abuse Screen Siemens Dimension RxL Max

Amphetamines/Methamphetamines Methadone

Barbiturates MethaqualoneBenzodiazepines Opiates

Cannabinoids PhencyclidineCocaineMetabolites Propoxyphene

Ecstasy

4. SJHMC Urine Drug of Abuse Screen

Triage

TOX Drug ScreenAmphetamines/Methamphetamines EcstasyBarbiturates Opiates (Heroin)

Benzodiazepines Phencyclidine (Angel dust)Cannabinoids Tricyclic antidepressants

CocaineMetabolites

5. Cheating Urine Drug Screens

Niacin: Multiple report to CDC on niacin use to block THC screening labi. Patient in Tucson: took 2 gm Niacin q4hr x 48 hours (!)


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Intoxication, Dependence, Withdrawal Nov. 2, 2010 Page 3

iii. EtOH, sedative/hypnotic drugs

iv. Severe respiratory depression with combination of sedatives.

Withdrawal Syndromes:i. Can mimic acute intoxication, usually when no past history available.ii. Significant clinical concern with alcohol, sedative/hypnotic withdrawal.

Clinical states most often requiring treatment:

a. Agitationb. Seizures

Treatment: Benzodiazepine

a. i.e., the withdrawal substance itself.b. (Rapid and significant cross-tolerance between EtOH and

sedative/hypnotics.)

7. Specific Drugs: See Appendix

DEPENDENCE

1. Substance Abuse Behaviors:

a. Curiosity: Minimal use1. Experimentation : More frequent use for fun, or in response to peer pressure.

2. Regular Use : Used every few weeks (or more).b. Problem Use

i. Single arrest for possession

ii. Episode of bingingiii. Being caught at school

iv. DUI

c. Substance Abuse (DSM-IV)

i. Maladaptive pattern of substance use leading to significant impairment ordistress:

1. Failure to fulfill major obligations at home, school, or work.

2. Recurrent use in hazardous situations: driving, operating machinery.3. Substance-related legal problems: arrests, etc.4. Use despite recurrent social problems: family, friends.

ii. Substance Dependence is not present.

d. Substance Dependence (DSM-IV: 3 of 7 criteria present)

i. Tolerance : Need for greatly increased amounts of the substance to achieveintoxication, or failure to produce symptoms at doses that would induce

symptoms in nave patients.

ii. Withdrawal:- Physical &/or behavioral symptoms characteristic of specific substance- The same (or related) substance is taken to relieve or avoid withdrawal

symptoms.

iii. Substance taken in larger amounts, over longer periods than intended.iv. Persistent desire : unsuccessful efforts to cut down or control substance use.

v. A great deal of time is spent in activities necessary to obtain, use, or recoverfrom the substance.

vi. Important social, recreational, or occupational activities are given upbecause of substance use.

vii. The substance use continues despite knowledge of recurrent problems dueto the substance use.


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2. Screening for Substance Abuse and Dependence

a. HEADSS: Home, Education/Employment, Activities, Drugs,Depression/Suicide, Sex

b. CRAFFT

i. Have you ever ridden in a CARdriven by someone who was high/drunk?

ii. Do you ever use alcohol/drugs to RELAX?

iii. Do you ever use alcohol/drugs when you are ALONE?

iv. Do you ever FORGET things while using alcohol/drugs?

v. Do your FAMILY/FRIENDS tell you to cut down on use?

vi. Have you ever gotten into TROUBLE while using drugs/alcohol?1. Two or more positives indicates Substance Abuse Problem2. Sensitivity = 0.92, Specificity = 0.64

WITHDRAWAL

1. Physiologic dependence

a. Results in part from down-regulation of receptors, with need for increasingdoses to achieve desired result: Tachyphylaxis

b. Presence of withdrawal symptoms occurs in absence of abused substance.2. Withdrawal Management Options

a. Avoidance of Withdrawal Symptoms: Opiate Replacement Tx

i. Methadone:1. Synthetic opioid developed in Germany in 1930s as an intestinal

antispasmodic agent.

2. Full mu-opioid agonist with long half-life (12 48 Hrs.)3. Methadone maintenance poor adolescent choice.

ii. Buprenorphine:1. Semi-synthetic partial mu-opioid agonist with very strong

receptor binding, displaces opiates from receptor sites.2. Developed in 1980s as an analgesic agent.

3. Used as opiate replacement once withdrawal symptoms are

present.4. Available as street drug in Tucson, not available for adolescents

otherwise.

iii. Diacetylmorphine1. Canadian study (2009) found IV diacetylmorphine more effective

than methadone in heroin treatment program.2. Problem: Diacetylmorphine is heroin (!)

b. Acute Symptom Management: Detox

i. Managed in licensed and accredited Detoxification facilities:

1. i.e. Sonora Behavioral Health (in Tucson).ii. Avoids need for opiate replacement therapy, but very high risk for

relapse must include intensive substance abuse counseling.iii. Only option available within Juvenile Detention Center.

c. Withdrawal Symptom Treatment Protocol:

i. CIWA: Clinical Instrument for Withdrawal Assessment1. Alcohol, Sedative/Hypnotics2. Assessment every 1 2 Hours:

a. 4 -10 Mild Symptomsb. 10 20 Moderate Symptoms

c. 20+ Severe Withdrawal Symptoms


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ii. COWS: Clinical Opiate Withdrawal Scale1. Assessment every 1 2 Hours:

a. 5 12 Mild Symptomsb. 13 24 Moderate Symptoms

c. 25 36 Moderately Severe Symptomsd. 36+ Severe Withdrawal Symptoms

iii. Symptom-Dependent Outpatient Management:

1. Assure adequate hydration: Gatorade 1 quart/day x 3 days2. Musculo-skeletal Symptoms: Ibuprofen 400mg TID prn

3. Anxiety, Nausea, Sleep Problems: Diphenhydramine 25 50 mgPO TID as needed.

4. Moderate Anxiety, muscle spasm: Lorazepam 1 2 mg PO TID asneeded.

d. PCJDC Over 24 month period:i. Alcohol/Sedative Withdrawals

1. 15 Adolescents (10 male/15 female)

2. Mild Symptoms: 15 Moderate: 0 Severe: 03. Complications: None

ii. Opiate/Opioid Withdrawals

1. 51 episodes among 42 adolescents (32 nales/10 females)

2. Substances: Heroin (IV, smoked), Oxycontin3. Maximum COWS Score under protocol: 24

4. Mild Symptoms: 30 Moderate: 21 Severe: 05. Complications: 0

6. Almost 25% had one or more re-detentions with need for repeatwithdrawal.

iii. Amphetamines: including Methamphetamine, Cocaine1. Only 8 adolescents symptomatic during this 2 year time period.

8. Appendix Specific Drugs: Opiates:

i. Respiratory depression primary concern: marked: Tidal Volume, RR

ii. Cardiovascular: HR, BP (Histamine release)

iii. Pupils (Miosis) [meperidine & propoxyphene pupils nl or ]iv. Seizures rare: can be due to hypoxia.

v. Most common adolescent narcotic: Dextromethorphan (DXM) OTC cough preparations

High doses: DXM Dextrorphana. Similar activity as ketamine & phencyclidine (PCP)

b. Hallucinations, HR, BP, agitation, ataxia, psychosis.

DXM can cause false + Urine Drug Screen for PCPvi. Prescription narcotic abuse also increasing: Vicodin, OxyContin, Tylox

vii. Heroin use increasing: smoke => snort=> shoot.

Cocaine:i. Catecholamine levels (similar to amphetamines, other stimulants).

ii. Sympathomimetic: HR, BP, QRS CVA, MI, Chest pain common, even without EKG changes

CNS: anxiety, agitation, paranoia, delirium, seizures, CVA.iii. Adrenergic Toxidrome: may rapidly progress to seizures, arrhythmias,


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stroke.

iv. Hyperthermia, Rhabdomyolysis, Placental abruption

v. Euphoria Anxiety, agitation, delirium, psychosis.

vi. Vasoconstriction can prevent heat dissipation: Temp (esp. Tucsonsummer) can reach 108 F.

vii. Magnans Sign: Sensation of bugs crawling under skin

Widespread excoriations, scratches, ulcers (freq. MRSA +)viii. Cocaine hydrochloride: po, iv, per nose.

Free base or solid (crack): smoked

Onset: Oral: 60 90 minutesNasal: 30 60 minutesIV/Inhaled: < 2 minutes

Durationbrief, Half-life = 60 minutesix. Cocaine + EtOH = ethyl-cocaine: prolonged duration

Datura stramonium (Jimson Weed Loco Weed)i. Powerful muscarinic agent hallucinogenic.

ii. 100 seeds 6 mg atropine (often smoked or made into tea).

iii. Anti-cholinergic Toxidrome: Hallucinations, confusion, bizarre behavior, HR, BP, dry mouth, pupils.

iv. Life threatening: Severe agitation, seizures, Temp.

Amphetamines

i. Similar to cocaine, but with longer duration of action.ii. Hemorrhagic and ischemic stroke, renal failure possible.

iii. Methamphetamine: prolonged use persistent psychiatric symptoms.

Phencyclidine (PCP)

i. Amps & Sherms: Dipping cigarettes into PCP dissolved in formaldehyde.ii. Coma, seizures, or BP, muscular rigidity: T, rhabdomyolysis.

iii. High-dose OTC Dextromethorphan Dextrorphan

Similar action as phencyclidine (PCP)

Ecstasy (MDMA: 3,4-methylenedioxymethamphetamine)i. Amphetamine-like: HR, BP, T, cerebral infarction, seizures.

ii. Also: Na, rhabdomyolysis, DIC, hepatic/renal failure.iii. Loss of serotonergic neurons: long-lasting cognitive defects

iv. Peak levels: 2 3 hours p.o.v. Onset: 20 minutes

vi. Duration: 4 5 hours

Contaminants: PMMA (paramethoxymethamphetamine),PMA (paramethoxyamphetamine): Lethal T.

Date-Rape Drugsi. Flunitrazepam (Rohypnol Roches as pills label Roche)

7 10x more potent than diazepam

Rapid onset: 15 20 minutes

Duration: 4 6 hours

Significant retrograde amnesia

Recent confusion: Any tablet labeled Roche


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ii. Gamma-Hydroxybuyrate (GHB)

Metabolite of GABA

Rapid onset: 15 minutes

Duration: 1.5 2 hours

Sedation, respiratory depression

Also: delirium, agitation, emesis, HR, T, amnesia.

Inhalant Abuse:i. Predominantly younger male adolescentsii. Higher rates of depression, suicidal ideation, history of physical/sexual

abuse.

iii. Solvent Abuse (gasoline, propane, Freon): CNS depression Stupor, ataxia,lethargy, excitation, agitation, hallucinations, seizures, nystagmus,respiratory depression.

Myocardial sensitization to catecholamine release: sudden death.

iv. Toluene (spray paint): K+, RTA, ataxia, permanent CNS defects.v. Amyl nitrate poppers: Methemoglobinemia

vi. Carburetor Cleaner: Mixed volatile solvents + Methanol 30%

Delayed onset (12 18 hours) of intoxication, metabolic acidosis.


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3. Further Reading:

1. Bayard M, McIntyre J, Hill KR, Woodside J, Jr. Alcohol withdrawal syndrome. AmFam Physician 2004;69:1443-50. (CIWA Scale)

2. CDC. Use of Niacin in Attempts to Defeat Urine Drugs Testing. MMWRWeekly, April 20, 2007 56 (15); 365-366.

3. Custer JW, Rau RE. The Harriet Lane Handbook, 18th ed. 2009:52-57 Drugs ofAbuse.

4. Haynes JF. Medical management of adolescent drug overdoses. AdolescentMedicine Clinics 2006; 17(2):353-379.

5. Kurtzman TL, Otsuka KN, Wahl RA. Inhalant abuse by adolescents. JAdolescent Health 2001;28;170-180.

6. Arciniegas S, Lowe MC, Gaspers M. Exchanging one poison for another: Anattempt to mask Urine Drug Screen Results. 2010 (in press).

7. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependentadolescents. Cochrane Database Systemic Rev 2009:CD006749.

8. Minozzi S, Amato L, Davoli M. Maintenance treatments for opiate dependent

adolescent. Cochrane Database Systemic Rev 2009:CD007210.9. NIDA and University of Michigan. Monitoring the Future Surveys, 1975 2009.

http://www.monitoringthefuture.org Annual surveys of high school substanceabuse over the past 33 years.

10. Oviedo-Joekes, E., S. Brissette, et al. Diacetylmorphine versus methadone forthe treatment of opioid addiction. N Engl J Med 2009; 361(8): 777-786.

11. Sanchez-Samper X, Knight JR. Drug abuse by adolescents: generalconsiderations. Pediatr Rev 2009;30:83-92.

12. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). JPsychoactive Drugs 2003;35:253-9.
http://www.monitoringthefuture.org/http://www.monitoringthefuture.org/

Intoxication, Dependence, Withdrawal 2010

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