Transcript 毒物与吸毒Poisons and drug abuse Department of Forenxic

毒物与吸毒
Poisons and drug abuse
Department of Forenxic Toxicology
SHIZHONG BIAN
Intentional Poisoning*
Advantages
Gender
Silent
Precise targeting
Depersonalized
Safe for attacker
Male
Female
Unknown
Profile
Background
Caucasian
Male
Average or above intelligence
Underachiever
Personality defect
Cowardly, nonconfrontational
Nonathletic
Neat and orderly, meticulous
Careful planner
Loner
Public
Physician
Political
Nurse
Other
Unknown
46%
39%
16%
71%
8%
4%
4%
5%
9%
*Source: Criminal Poisoning (2000)
J. H. Trestrail, Humana Press
Properties of Ideal Poison
Undetectable by senses
Soluble
Delayed effect
Easily obtained
Not traceable
Symptoms mimic actual disease
Chemically stable (?)
Undetectable by instrumentation
Potent
“The dose makes the poison”
Potencies of Poisons
Agent
Lethal dose
Botulinum toxin
0.05 mg
Ricin
0.5 mg
Strychnine
100 mg
Sodium arsenite
200 mg
Sodium cyanide
250 mg
Thallium
1000 mg
NB: A dime is 2300 mg
Sources of Poisons
Commercial
Laboratories
Underground catalogs
Antique drug collections
Hobbies/natural sources (e.g., plants)
Pesticide Poisons of Note
Synthetic –
Organophosphates
Carbamates
Paraquat
Fluroacetate (1080 bait)
Plant-derived – Oleander
Poison hemlock
Mushroom
Ricin
Atropine/belladonna
Nicotine
Strychnine
Cyanogenic glycosides
• 毒物与中毒的概念：某种物质进入机体后，通过化
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学或物理化学作用，使组织细胞结构发生改变、代
谢或功能遭受损害，从而引起健康障碍、疾病或死
亡者，称为中毒。凡在一定剂量时能引起中毒的各
种物质，就称为毒物。
毒物与药物不能机械地划分。
毒物广泛分布于人的周围环境中。
毒物的概念只是相对的，没有在任何条件下都可产
生毒性作用的毒物。食盐一次服用15~60克即有碍
于健康，一次用至200~250克，可因其吸水作用和
所致的离子平衡障碍引起死亡。
• 毒物的分类：毒物的种类繁多，目前尚无
一个完善的分类法。为了法医学鉴定中毒
的需要，在分析中毒症状病理变化时，宜
采用按毒理作用分类；在作法医化学分析
时则采用按毒物的化学性质分类；为追溯
毒物来源，则可采用按毒物用途、来源和
作用混合分类。
• 按毒物的化学性质分类
1.挥发性毒物 氰化物、醇、有机磷农药
2.非挥发性毒物 巴比妥类催眠药、吗啡
3.金属毒物 砷、汞、钡、铬、锌
4.阴离子毒物 强酸、强碱、亚硝酸盐
5.其他毒物 煎毒碱、CO、硫化氢
• 按毒理作用分类
1、腐蚀毒 强酸、强碱、酚类
2、实质毒 砷、汞
3、酶系毒 有机磷、氰化物
4、血液毒 CO、亚硝酸盐及某些蛇毒等
5、神经毒 醇类、麻醉药、催眠药、士的
宁、烟碱等抑制或兴奋中枢神经的药物。
• 混合分类法
1、腐蚀性毒物
2、毁坏性毒物（即实质毒）
3、障碍功能的毒物
4、农药
5、杀鼠剂 敌鼠钠、安妥等
6、有毒植物 乌头、钩吻等
7、有毒动物 蛇毒、河豚、斑蝥等
• 中毒发生的条件
1、毒物的量。中毒量；致死量（g/kg体重）
2、毒物的性状。气态；液态；固态。
3、毒物进入机体的途径。心脏或血管内注射＞呼吸
道吸入＞腹腔注射＞肌肉注射＞皮下注射＞口服＞直肠灌注。
4、毒物的协同作用与拮抗作用。
5、机体状态。体重；年龄；性别；健康状态；习惯性或成
瘾性；过敏性；体内蓄积。
6、其他。
• 毒物的转运、转化及其法医学意义
1、吸收。消化道；呼吸道；皮肤吸收；注
射吸收。
2、分布。毒物在体内的分布并非均匀。
3、代谢。氧化；还原；水解；结合。
4、排泄。肾；胆道；其他（上皮、皮脂腺、
唾液腺、乳腺、消化液）。
中毒的法医学鉴定
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案情调查
症状分析
现场勘验
尸体检查
检材采取
毒物分析结果的评价
中毒尸体挖掘取材的
价值
Poison plants readily available from
nurseries, arboreta, backyards, wild areas
Foxglove
purpurea
Datura
digitalis
atropine
Not visible: Lupine (lupanine)
Oleander Autumn Poison Lantana
crocus hemlock
cardiac colchicine coniine
glycosides
Ricinus communis
(Castor bean)
lantadene
ricin
Top 5 Homicidal Poisons
Agent
Frequency
Target
Arsenic
31%
Cyanide
9%
Strychnine
6%
Morphine
3%
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Chloroform
2%
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Energy generation
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Nervous system
Analysis
Evidence in vicinity of victim
Pill bottle, drug paraphernalia
Food, beverage leftovers
Symptoms
Acute
Chronic
Sampling
Organs, fluids
Accessory material
Detection
Analytical instrumentation
HPLC, GC, Mass Spec
Motivation
Love, money, power
Disguised as random
Poison Symptoms
Constricted/dilated pupils (opioids, organophosphates)
Breath odor (arsenic – garlic)
Hair loss (thallium)
Convulsions (strychnine)
Paralysis (botulism)
Coma (depressants, hypnotics)
Skin color (CO – cherry red; nitrites – blue)
Skin appearance (arsenic – hyperkeratosis, warts)
(dioxin – chloracne)
TCDD (dioxin) – Chloracne
Poisoning of Victor Yushchenko just before Ukraine presidential election
Dioxin (TCDD) Sensitivities
Species
LD50 (µg/kg)
Guinea pig
Rat
Monkey
Human
Mouse
Rabbit
Hamster
2
40
50
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130
200
4000
Autopsy samples
Organs (brain, liver, kidney, muscle)
Blood (heart, peripheral)
Vitreous humor
Bile (insoluble metabolites)
Urine (soluble)
Gastric contents (alkaloids)
Hair
Bone
Maggots
Environmental/Accidental Contamination
Differential diagnosis
Accidental death or homicide?
Compensable injury or carelessness?
Background that could confound interpretation
Verify authenticity/natural source or show adulteration
How did the mass poisoning occur?
Substitution of inferior/contaminated component?
Track source of environmental contamination
Environmental justice for underserved?
Safeguards not enforced
Children often victims
Which companies are breaking the law?
Marine Toxins in Food
Pufferfish
Delicacy in Japanese restaurants
Gives tingling of lips when properly prepared
Tetrodotoxin concentrated in liver and ovary (removed)
Blocks sodium channel in nerves
Fatal in excess (lethal dose 1 mg)
Shellfish Tainted by Red Tide (3 examples)
Saxitoxin – Paralytic shellfish poison (blocks sodium channel), potentially fatal
Domoic acid – Amnesic shellfish poison (glutamate neurotransmitter analog)
Disorientation, loss of short term memory at moderate doses
Fatal excitotoxin activity at higher doses
Okadaic acid – Diarrhetic shellfish poison (phosphatase inhibitor), nonfatal
Harmful Algal Blooms
Thought increasing due to coastal pollution, ocean warming
Of 4,400 known algal species, >1% produce toxins
Known causes of wildlife epidemics
Marine mammal mortality off California coast from domoic acid
Accidental Food Contamination
Iraq 1972: 5-6,000 people hospitalized, 10% died.
Seed grain donated with methyl mercury antifungal agent.
Distributed 100,000 tons to farmers, improperly identified.
Grain (wheat, barley) mistakenly used to make bread.
Michigan 1973: Nearly 2 million livestock destroyed.
Several hundred pounds PBBs mixed with dairy feed.
Coverup by company and state officials compounded problem.
Spain 1981: 11,000 people hospitalized, >500 died.
Industrial rapeseed oil from France containing aniline refined.
Refining process produced toxic components.
Resold fraudulently as cooking oil (59 tons) after mixing olive oil.
Adulturation of vegetable oils (soybean/canola in olive) frequent.
Biochemical components becoming available for detection.
Commercial Activity - Mercury
A woman holds a victim of
"Minamata Disease", or mercury
poisoning, in Minamata, Japan,
in 1973. The girl has a malformed
hand, like many victims of the
disease who suffer from physical
deformities and mental retardation.
Chisso Corporation, a Japanese
fertilizer, petrochemical and
plastics company, dumped an
estimated 27 tons of mercury
compounds into Minamata Bay
between 1932 and 1968. Up to
10,000 people were affected by
eating seafood from the bay.
Many sources of mercury exist, either natural (fish) or associated with
human activity (chloralkali plants, gold mines, effluent from power plants).
Elemental form is methylated by micro-organisms in the environment.
Commercial Activity - Lead
Targets: Blood cells (anemia), kidney (gout), sperm (infertility)
Nervous system most sensitive target
Adults: Occupational exposures
Lead smelters, battery factories, lead additives
Painters got peripheral neuropathy (wrist drop)
Children: Colic (acute) and mental retardation (chronic)
Legacy of leaded paint and gasoline
• Eating peeling paint (many inner cities)
• Playing in contaminated yards (e.g., Oakland)
Commercial activity – Acrylamide
Sweden 1997: Hallandsas tunnel construction halted.
Acrylamide used in grouting to prevent water seepage.
20 workers experienced neurological symptoms (reversible).
Several cows grazing nearby showed severe neural effects.
Dead fish found in hatchery supplied by water from tunnel.
Acrylamide found in ground water near tunnel.
Sensitive methods developed to detect acrylamide showed
high background levels in humans.
Surprisingly high levels found in fried foods (potato chips).
Potential exposures in typical labs using acrylamide gels
(including DNA identification labs).
Intracellular Targets of Neurotoxins
Ion channels – Signal conduction
Sodium
Potassium
Calcium
Chloride
Synaptic region – Neurotransmitter processing
Release
Reuptake of excess
Receptor response (stimulate, block)
Channels and receptors - multigene families
Located in different parts of the nervous system
Responsible for differential effects
Uses of Amphetamines and Derivatives
Treatment for narcolepsy - 1930’s
Maintaining military alertness - 1940’s
Occupational alertness (students, truckers) – 1950’s
Appetite suppressant
Suppress childhood attention deficit disorder
Dietary supplement (ephedrine) as “natural energizer”
Opioid Analgesics
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Background
Pharmacokinetics
Pharmacodynamics
Tolerance and
Dependence
Side Effects and
Toxicity
Pharmacotherapy
Opioids:
Background
• Poppy (Papaver
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somniferum)
Morphine isolated in
1803 (“Morpheus”)
– German chemist,
Serturner
• Codeine isolated by
accident in 1830s
– French chemist,
Robiquet
Opioids:
Background
• Heroin
– made from morphine,
1898, Bayer Co.
– advertised as having
all benefits, none of
liabilities of morphine
and codeine
Opioids:
Background
• Harrison Narcotics Act
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of 1914
1924, Heroin added
Current Use levels:
illicit
Morphine/Heroin:
Pharmacokinetics
• Absorption
– routes of
administration
– physical properties:
base; poor lipid
solubility (except
heroin)
– peak absorption rapid
via IV and inhalation
Morphine/Heroin:
Pharmacokinetics
• Distribution
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lungs, liver, spleen
blood protein binding
pass placental barrier
difficulty passing
blood/brain barrier
– active system pumps
opiates out of brain
– Heroin is very lipid
soluable--exception
Morphine/Heroin:
Pharmacokinetics
• Inactivation
– Metabolism
• Heroin metabolized to monoacetylmorphine, then
to morphine in brain
• Morphine metabolized by conjugation; P450
enzymes in liver
• Morphine 1/2 life is 2 hours
– Elimination
• 4 hours 1/2 life
Morphine/Heroin:
Pharmacodynamics
• Cellular sites and mechanism(s) of action
– 1973, opioid receptors discovered
– Mu, Epsilon, Delta, Kappa
– Mu receptors are metabotropic:
• activation enhances flow of K+ out of cell and/or
decreases activity of voltage-sensitive Ca++
Morphine/Heroin:
Pharmacodynamics
• Brain sites of action
– Medulla
– Basal ganglia
– Hippocampus
– Amygdala
– hypothalamus
Morphine/Heroin:
Pharmacodynamics
• Brain sites of action (cont.)
– Periaqueductal grey
– locus coeruleus
– Frontal cortex
– Inhibitory interneurons in VTA (GABAr)
Morphine/Heroin: Tolerance
and Dependence
• Tolerance
– Fastest to euphoric and analgesic effects
• 40-50x non-tolerant dose
– Cellular/Pharmacodynamic (not metabolic)
• decreased receptor sensitivity
Morphine/Heroin: Tolerance and
Dependence
• Dependence
– Withdrawal peaks at 23 days
– Naloxone test for
dependence
– Seldom lifethreatening, “flu-like”
– Methadone treatment
of withdrawal
Morphine/Heroin: Side Effects
and Toxicity
• Lethality
– lowers seizure threshold
– tolerance to desired v. lethal effects
– life style v. direct effect of drug
Morphine/Heroin:
Pharmacological Treatment
• Methadone
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maintenance
Naltrexone/Naloxone
Buprenorphine
Rapid detoxification