Poisoning in Children
Download
Report
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