Transcript Poisoning in Children

Substance Abuse in Adolescents
Yedidia Bentur, MD
Israel Poison Information Center
Rambam Medical Center
Faculty of Medicine, Technion,
Haifa, Israel
“We live in a decadent age.
Young people no longer respect their
parents.
They are rude and impatient.
They frequent taverns and have no
self-respect.”
Inscription on Egyptian tomb circa 3000 B.C.
Anti Drug Authority, Israel 2001
 12 – 18y,  one use/year
 Substances
 volatiles 7.4%
 medications w/o indication 6.1%
sedatives 4.8%, methylphenidate 2.9%
 illegal drugs (w/o cannabis) 5.4%
Ecstasy 2.7%
 cannabis 5%, (USA 20% - 50%)
marijuana 4%, hashish 3.3%
Poison Information Center Data
Adolescents, 2003
Israel
USA
32 (0.16%)
14, 875 (0.6%)
Cannabis
Amphetamines
MDMA
Caffeine
Opioids
Cannabis
LSD
MDMA
Volatile Substance Inhalant Abuse (VSIA)
 Recreational use of volatile substances
 Since 19th century,  use since 1960s
 Age: 14 - 22y (9 – 29y)
 Inexpensive, available, legal,
easy to conceal and handle,
perceived erroneously as safe
 Sudden death with negative autopsy findings
Classification of inhalants
 Volatile solvents
 adhesives (glue sniffing), thinners, lighters,
correction fluid, dry cleaning, gasoline
 Aerosols (propellants and solvents)
 spray paint, hair spray, deodorizers
 Gases
 freons (air conditioning), halothane,
N2O (whipped cream, laughing gas)
 Nitrites
 sexual stimulants:
amyl nitrite, butyl nitrite, cyclohexyl nitrite
Inhalants
Exposure
Dose inhaled depends on:
 concentration in preparation
 mode of inhalation
(container, aerosol, cloth, plastic bag, etc.)
 duration
 number of exposures
Levels x100-1000 occupational thresholds
Factors affecting clinical response
Dose
Genetic factors
Diet
Alcohol consumption
Smoking habits
Concomitant drugs
Physical activity
Glue sniffing - toluene
 Absorption 50%
 Tmax 15 – 30min
 Distribution to adipose tissues
 Metabolism: liver, extensive (80%)
 inhibited by ethanol
 P450 (CYP 1A1) and ALDH2 polymorphism
 oxidation to benzoic acid 
conjugation with glycine  hippuric acid
Toluene (2)
Excretion
 < 20% by inhalation, unchanged
 urinary hippuric acid (filtration + secretion)
Elimination
 biphasic; triphasic in workers
 terminal T½ 15-90h
Chronic abuse: induction of P450
  hippuric acid,  exhaled unchanged
Mechanism of toxicity
 Perivascular myelin loss,
degeneration of white matter
(cerebral cortex, cerebellum)
 Hypoxemia (freons, plastic bag)
 Aspiration
 Hypoperfusion
 Sensitization of myocard to catecholamines
 Irritation (freons)
 Frostbites (freons)
Clinical manifestations
 Nausea, vomiting, bronchospasm
 Confusion, psychomotor impairment,
drunkenness, disinhibition, dizziness,
headache, slurred speech, drowsiness, ataxia
 Hallucinations, delusions, mydriasis
HR, BP, respiration, coma, seizures
 Death: anoxia, respiration, arrhythmias
Clinical manifestations (2)
Distal renal tubular acidosis (toluene)
Hemolysis (nitrites)
Hepatitis (halogenated hydrocarbons)
Head trauma (freons – air conditioning)
Burns (concomitant smoking)
Normal
Inhalant abuse
Clinical manifestations (3)
Sequelae: neuropsychiatric, irreversible
 epilepsy, atrophy, polyneuropathy
  cognition, psychosis
Withdrawal
 tolerance, psychological addiction
 resembles alcohol withdrawal
Fetal solvent syndrome (glue and gasoline)
Diagnosis
 High index of suspicion – thorough history
 unexplained neuropsychiatric / C-V manifestations
 ECG monitoring
 High anion gap metabolic acidosis (esp. toluene)
 Urinary hippuric acid:
 used in occupational biomonitoring
 interference: dietary benzoic acid
(prunes, cranberries, plums, Chinese preserves, black tea)
 Toluene blood and urine levels: not useful
Treatment
 Removal
 Supportive
 Avoid catecholamines:  arrhythmias
 Tachyarrhythmias: propranolol IV, esmolol IV
 No specific antidote
Cannabis
sativa
Cannabis
Cannabis sativa
Known in Asia for > 5,000y
61 cannabinoids:
 9- tetrahydrocannabinol (THC): psychoactive
 8-THC, cannabidiol, cannabinol
Smoked (joint, 20mg THC), eaten (cookies)
“Gateway” drug
Medicinal – dronabinol (Ronabin, 2.5mg)
Common types of cannabis
Marijuana (grass): leaves, flowers, stem (1-5% THC)
Hashish: dried and compressed resin (10% THC)
Hashish oil (30-50% THC)
Charas: resin; ~20% THC (India)
Bhang: leaves (India)
Dagga: (South Africa)
Kef
Toxicokinetics
Bioavailability: oral 10-20%, lung 20-30% rapid
Onset 10-60min, Tmax 2-4h
Distribution to adipose tissues (brain)
Metabolism: hydroxylation 11-OH--THC (active) 
11-nor-9 carboxy--THC (inactive)
T½ 20-30h, chronic user 5d (1-12d), duration 1-8h
Individual variability (experience, tolerance)
Toxic dose:
psychoactive 3-15mg, lethal 30mg/kg
Mechanism of toxicity
Cannabinoid receptors
 nervous system (CB1):  of transmitter release
 immune cells (CB2): modulate cytokine release
 testis (CB1), LH, prolaction
Endocannabinoids: anandamide, 2-arachidonyl-glycerol
Stimulant
Sedative
Hallucinogen
Catecholamine (dopamine) release (abuse)
Inhibition of sympathetic reflexes
Neurotoxicity of cannabis
Acute effects
 mood
 cognition
 behavior
 psychmotor
Chronic effects
 antimotivational
 psychosis
 dependence
Clinical manifestations
Euphoria,  sensory awareness,
time – space distortion, palpitations, sedation
 reaction time, incoordination,  performance
Impaired memory, depersonalization,
hallucinations, paranoid psychosis
Tachycardia, orthostatic hypotension,
conjunctival injection, slurred speech, ataxia
Clinical manifestations (2)
Chronic users:
manic, schizophreniform, confusional psychosis
acute & chronic respiratory toxicity
Children (cookies): pallor, fine tremor, ataxia,
hypotonia, coma, apnea, HR
Contaminants: pulmonary aspergillosis, paraquat
Withdrawal: after 180mg/d, 2-3wks; lasting 48h
restlessness, insomnia, anxiety, tremor, hot flushes
Diagnosis
High index of suspicion – thorough history
HR, conjunctival injection, altered mood / cognition
Urine THC: after 1h  days (acute), weeks (chronic)
 no correlation to severity
 false negatives:
dilution, lemon juice, vinegar, bleach, salt, Visine
 false positives: NSAIDs
 passive smoking  positive results
R/0 other drugs of abuse
Treatment
Reassurance
Benzodiazepines
Sinus tachycardia: β blockers ( rarely needed)
Orthostatic hypotension: IV fluids
No specific antidote
Not life threatening
Ecstasy
3,4-methylenedioxymethamphetamine - MDMA
(hallucinogenic amphetamine)
‫אקסטזי‬
‫אקסטה‬
‫כדור‬
‫מיצובישי‬
‫עגול‬
‫‪ 120mg‬‬
‫‪X10-100 variability‬‬
Toxicokinetics
 Absorption, oral: rapid
 Onset of action: 30-60 min
 Peak action: 90 min
 Duration of action: 4-6 h (could be >8 h)
 Metabolism: liver, P450 and N-demethylation,
some metabolites active
 Urine excretion: 65% unchanged, 35% - metabolites
 Elimination kinetics: non-linear
Mechanism of action
 Hallucinogenic and stimulant
 Serotonin release followed by prolonged depletion (wks)
 Permanent destruction of serotonergic nerve endings
 in every experimental model
 Stimulate NorE release with  dose
 stimulate - and -adrenergic receptors
 SIADH
Pattern of use
 Usually at rave parties
 Hours of dancing
 Heavy water intake
 Up to 10 tab / night
 Repeated use → reinforcement
Clinical manifestations
 Toxic dose: variable
 Can be delayed for hours
 Unpredictable severity of effects
 Severe poisoning and death - even after 1 tablet
 Causes of death:
cardiac arrhythmias, hyperthermia, hyponatremia
Clinical manifestations (2)
 “Positive”: mood, euphoria, talkative, intimacy
 “Negative”: HR, anxiety, anorexia, bruxism, mydriasis
 Next day:
myalgia, somnolence, depression, concentration
 Repeated use: tolerance to the positive effects
 Frequent use, dose:  negative effects
Clinical manifestations (3)
 Nausea, vomiting
 Chest pain, HR, BP, arrhythmias, MI (rare), ARDS
  temp., dehydration, rhabdomyolysis, ARF, DIC
 Seizures, brain hemorrhage / infarct / edema
  Na, myoglobinuria, metabolic acidosis
 Hepatitis
 Serotonin syndrome
Clinical manifestations (4)
 Emotional instability, insomnia
 Confusion, depression, suicidal thoughts
 Flashbacks, hallucinations
 Impaired cognition
 Psychosis (paranoid), panick attack
Diagnosis / Evaluation
 High index of suspicion - thorough history
 Unexplained neuropsychiatric / C-V manifestations
 Na, K, blood gases, CPK, myoglobin
 ECG & cardiac monitoring
 R/O complications, other diagnosis
 Urine assay: qualitative (usually), quantitative
 Blood level: not clinically useful
Differential diagnosis
 Toxicological causes of agitation and seizures
 cocaine, amphetamines, TCA, MAO - I, isoniazid
 Non-toxic causes
 alcohol withdrawal
 intracranial hemorrhage
 manic behavior, psychosis, seizure disorder
 metabolic disorder (e.g. hyperthyroidism)
 cardiovascular abnormalities
Management
 Do not delay treatment !
 Sedation: benzodiazepines
caution neuroleptics (e.g. haloperidol):
 seizures,  temp., arrhythmias, dystonia
 Supportive
 oxygenation, ventilation – as needed
 hypertension: nitroprusside
 seizures: benzodiazepines
 hyperthermia: sedation, cooling, hydration, dantrolene
 hyponatremia: water restriction? saline (0.9%? , 3%?)
General warning signs
Changes in school behavior
Mood changes
Dropping out of usual activities
Changed physical appearance
New friends / loss of old friends
Missing items / money
Change in sleep patterns
Depression / anxiety
Cannabis