“Hope is the crystal meth of emotions it hooks you fast and kills you
hard.”
― Jennifer Donnelly, Revolution
― Jennifer Donnelly, Revolution
Toxicology. It’s not
always about illegal drugs.
It is the study of undesirable effects on humans of prophylactic &
therapeutic drugs, food & beverage additives, and industrial chemicals integrated
into consumer goods. It is the study of
symptoms, mechanisms, treatments and revealing of poisoning, particularly the
poisoning of people.
Britney is Toxic
Milestones of Toxicology
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Toxic
Agents
- Are common CNS depressants
- Cause disorientation, euphoria, confusion and may progress to unconsciousness, paralysis and even death
- Symptoms of alcohol intoxication begin when the concentration is > 0.05% w/v ( >50ng/dL blood alcohol).
Methanol
- Is a commonly used solvent and a contaminant of homemade liquors
- It is converted first to formaldehyde, then finally to formic acid in the liver
- Fatal dose: 60-250mL
Isopropanol (rubbing alcohol)- It is metabolized to hepatic ADH to acetone
- Fatal dose: 250mL
Ethylene glycol
(1,2-ethanediol)
- It is a common constituent of hydraulic fluid and antifreeze
- It is converted to oxalic acid and glycolic acid
- Production of final products leads to deposition of calcium oxalate crystals in renal tubules
- Fatal dose: 100 grams
Carbon Monoxide (CO)
- It is a colorless, odourless, tasteless gas; very toxic substance
- It is produced by incomplete combustion of carbon-containing substances like gasoline engines, organic materials in fire and cigarette smoke.
- Toxic effects are manifested by binding with heme proteins (cytochromes, myoglobin, and haemoglobin
- It has higher affinity for haemoglobin than does oxygen – impairs oxygen transport by binding to haemoglobin producing carboxyhemoglobin
- It inhibits cellular respiration and electron transport
- Net effect: tissue hypoxia
- Toxic levels: 20% CO
- Indicator of toxicity: “cherry-red” color of the face
- Sample for testing: EDTA whole blood
- Method for testing: co-oximetry (carboxyhemoglobin measurement)
- It can exist as a solid, gas or in solution; a super toxic substance
- It is a component of insecticides and rodenticides; common suicide agent
- It is also a pyrolysis product – burning of plastics
- It expresses its toxicity by binding to iron (ferric and ferrous forms) containing substances like haemoglobin and cytochrome oxidase – resulting to tissue and cellular hypoxia
- It inhibits cellular respiration, electron transport and ATP formation
- It has characteristics “odor of bitter almonds”
- Antidote: sodium thiosulfate, amyl and sodium nitrite
- Toxic symptoms: tachypnea, convulsions and coma
- Toxic levels: >2ug/mL
Metals
All metals can be
toxic if ingested in large quantities and absorbed in their ionized form
Arenic
Component of ant
poisons, rodenticides, paints and metal alloys
It is a common
homicide or suicide agent; common agent of heavy metal poisoning
It inhibits
sulfhydryl enzymes throughout the body
Exposure to this
chemical occurs in smelting industries and agriculture
It expresses its
toxicity by high affinity binding to the thiol groups in proteins
It has
characteristic “odor of garlic” and “metallic taste”
The use of hair
and nails (“Mees lines”) as specimens are important in the evaluation of
long-term (chronic) exposure – ion emission spectroscopy
Blood and urine
specimens – for short-term (acute) exposure
Acute fatal
dosage: 120mg
Method for
testing: Reinsch test, atomic absorption spectrophotometry
Cadmium
It is utilized in
electroplanting and galvanizing
It is a
significant environmental pollutant – pigment in paints and plastics
Poisoning can
result from ingestion of acidic foods stored or prepared in metal containers
made up of cadmium
Toxicity may
result to destruction of type 1 epithelical cells in the lung and decreased
resistance to bacterial infections
It may also
accumulate in renal tubules causing tubular damage
Toxic renal
indicator: (+) GGT in urine sample
Lead
Is a component of
household paints and a potent enzyme inhibitor
It combines with
the matrix of bone and can persist in this area for a long time (half-life -32
years)
Exposure to this
metal results to encephalopathy, birth defects and compromised immunity
Low-level
exposure may cause behavioural changes – hyperactivity and attentional deficit
disorder, and also affect intelligence quotient scores (decrease)
Vitamin D and
heme synthesis pathway are affected – lead blocks delta aminolevulinic acid
(ALA) synthetase, producing anemia.
It has a
characteristic “wrist drop or foot drop” manifestation
EDTA and
dimercaptosuccinic acid (DMA) are used for treatment as therapeutic chelaters –
to remove lead from soft tissues and bone.
Toxicity dose:
>0.5mg/day
Fatal dose: 0.5g
CDC cutoff for
normal lead in children: <10 ug/dL
Toxic blood
levels: >70 ug/dL (definitive lead poisoning)
Drugs of Abuse
Almost all drugs
of abuse are basic drugs which contain berozene rings; barbiturates are acidic
drugs
Many of the
abused drugs act directly on dopaminergic neurotransmitter systems, especially
the limbic system (smell brain).
A positive drug
screening test cannot differentiate casual user from chronic or habitual user,
likewise detect the time frame of using the drug or dose of the drug taken
Designer drugs –
modified forms of established drugs of abuse
Amphetamines
Therapeutically
used for treating narcolepsy and attentional deficit disorder
Increases mental
alertness and physical capacity and has anorectic property
Structurally
related to dopamine and cathecolamines
Ephedrine,
pseudoephedrine and phenylpropanolamine = amphetamine-like compounds
3,4-methylenedioxymethamphetamine
(MDMA or ecstasy), a derivative of methamphetamine is a popular recreational
abused drug
Hyperpyrexia (^
body temp) is a sign of acute intoxication
Toxic effects:
hypertension, cardiac arrhythmias and convulsions, pancytopenia
Annabolic steroids
They are
chemically associated to the male hormone testosterone (dihydrotestosterone and
testosterone)
It improves
athletic performance by increasing muscle mass
Toxic effects:
chronic hepatitis, atherosclerosis, abnormal platelet aggregation and
cardiomegaly
Cannabinoids
The naturally
occurring cannabinoids are marijuana and hashish
Tetrahydrocannabinol
(THC) is the most potent component or the psychoactive substance of marijuana
THC a lipophilic
substance, distributes in the adipose tissues; it induces a sense of well-being
and euphoria
THC is also
associated with impairment of short term memory and intellectual functions
After a single
use, THC-COOH can be detected in urine for 3-5 days; up to 4 weeks for chronic
user.
Urinary
metabolite: 11-nor-deltatetrahydrocannabinol (THC-COOH)
Physiologic
effects: reddening of the conjunctive and tachycardia
Cocaine (crack)
Is an alkaloid salt
that can be taken directly (insufflations of IV) or by inhalation
It is derived
from coca plant (Erythroxylon) and used as additive to some foods
It is used as
local CNS stimulant that elicits a sense of excitement and euphoria; increases
physical activity
It easily pass
the placenta and mammary glands
Classically has
not been considered as an addictive drug
It can cause
sudden death due to direct toxicity on myocardium (cardiac toxicity)
Overdosage of
this drug may result to violent behaviour; high abuse potential
Prozac is used to
inhibit the action of this elicit drug
For single use,
it can be detected in urine for up to 3 days; up to 20 days for chronic users
Toxic effects:
hypertension, arrhythmias, seizures and myocardial infarction
Urine metabolite:
benzoylecgonine (sensitive and specific indicator)
Opiates
They are capable
of analgesia, sedation and anesthesia
Derived
chemically from opium poppy
Opium, morphine,
and codeine – naturally occurring substances
Heroin,
hydromorphone (Dilaudid) and oxycodone (Percodan) – chemically modified forms
of opiates
Meperidine
(Demerol), methadone (Dolophine), propoxyphene (Darvon), pentazocine (Talwin)
and fentanyl (Sublimaze) – common synthetic opiates
Heroin is highly
addictive; morphine is a powerful analgesic; codeine is antitussive
Morphine binds to
mu-receptors in the limbic system (CNS) producing analgesic effect
Morphine and
meperidine increase liver and pancreatic enzymes
Methadone is a
nonbicyclic drug that binds with morphine in the brain
Darvon overdose
combine with alcohol – is a major cause of drug-related death
Morphine and
codeine are substances commonly tested
Major
metabolites: N-acetylmorphine (heroin) and morphine
Antagonist for
opiate overdose: nalaxone (narcan)
Toxic effects:
respiratory acidosis, myoglobinuria and cardio pulmonary failure
Phencyclidine (angel dust angel
hair)
Is a depressant,
stimulant, and has hallucinogenic and anaesthetic properties
It can be
ingested or inhaled by smoking
About 10-15% is
unchanged when excreted in urine
Major metabolite:
phencyclidine HCI
Toxic effects:
stupor and coma
Sedative Hypnotics
They have
therapeutic roles and they are CNS depressants
Examples:
barbiturates and benzodiazepines
Secobarbital,
pentobarbital, Phenobarbital – commonly abused barbiturates
Diazepam
(Valium), chlordiazepoxide (Librium), and lorazepam (Ativan) – commonly abused
benzodiazepines
They are used
also to potentiate the effects of heroin
Diazepam has a
clinical use for rapid control of acute seizure activity
Phenobarbital
structurally resembles phenytoin (Dilantin)
Toxicity of these
agents are initiated by ethanol
Major metabolite:
secobarbital (barbiturates)
Toxic effect:
respiratory depression
Celebrity Drug Addiction
 |
| Whitney Houston |
 |
| Amy Whinehouse |
For more shocking pictures because of drug addiction, you can visit the following sites
- From drugs to mugs: Shocking before and after photos show how drug addiction takes devastating toll on faces of users
- Celebrity addicts: Who dies, who survives, and why?
- Music Stars Before and After Taking Drugs
Terminologies:
·
Acute Toxicity: single, short-term exposure
to a substance
·
Chronic Toxicity: repeated exposure for
extended period of time
·
TD50: is the dose that would be predicted
to produce a toxic response in 50% of the population.
·
LD50: is the dose that would
predict death in the 50% of the population
·
ED50: is the dose that would be
predicted to be effective or have a therapeutic benefit in 50% of the
population.
