1. Carcinogens 2. Mutagen 3. Reproductive hazards 4. Teratogen

1. Short term 2. Appears shortly after exposure (<24 hrs) 3. Can be form single exposure

1. With latency 2. It takes a long period of time before you see the effects (>3 months) 3. Exposure can be due to repeated doses

Toxicology Flashcards by MAE AMOR D. CHIOCO

Study of poisons

TOXICOLOGY

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The basic science of poisons (old)

TOXICOLOGY

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The study of the adverse effects of chemical
agents on biological systems (new)

TOXICOLOGY

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any substance that causes harmful effects
upon exposure

Poison

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 Substances not absorb produces local effects

Poison

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Major areas of Toxicology

Clinical
Descriptive
Forensic
Mechanistic

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study inter relationships between
toxic exposure and disease states

Clinical

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results from animal
experiments to predict what level of
exposure will cause harm in humans; risk
assessment

Descriptive

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primary concern in medico-legal
in toxic exposure consequences

Forensic

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cellular and biochemical
effects of toxins

Mechanistic

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A substance with a capacity to produce
injury or illness

TOXIC SUBSTANCE

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Types of Toxic Hazardous materials

Chemical Agents and Drugs of Abuse
Physical Agents
Biological Agents

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EFFECTS OF TOXICANTS

Irreversible
Acute Effects
Chronic Effects

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Irreversible

Carcinogens
Mutagen
Reproductive hazards
Teratogen

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Acute Effects

Short term
Appears shortly after exposure (<24 hrs)
Can be form single exposure

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Chronic Effects

With latency
It takes a long period of time before you see the
effects (>3 months)
Exposure can be due to repeated doses

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MAJOR FACTORS THAT INFLUENCE TOXICITY

Route of admission
Duration and Frequency of exposure
Dose or Concentration

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What are the Route of admission

Inhalation
Ingestion
Injection

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via mouth/nose, then to the
lungs, and to the bloodstream

 Inhalation

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mouth to stomach to
bloodstream

Ingestion

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cuts/punctures/wounds and
then to the bloodstream

Injection

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The frequency of the exposure affects the
concentration at the target site – can build
up to a steady level

Duration and Frequency of exposure

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The frequency of the exposure affects the
concentration at the target site can build
up to a ?

Steady level

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the amount of chemical entering the
body

Dose or Concentration

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MEASURE OF TOXICITY/EFFECTIVE DOSE

LD50 TD50 ED50

the dose of a chemical which produces death in 50% of a population.

LD50

the dose that would be predicted to produce a toxic response in 50% of the population.

TD50

the dose that would be predicted to be effective or have therapeutic benefit in 50% of the population.

ED50

is the biotransformation of chemicals into something less harmful

Detoxification

ELIMINATION OF TOXINS

1. Excretion through the kidneys, liver, and lungs 2. Detoxification is the biotransformation of chemicals into something less harmful 3. Storage in fatty issue

What are the organs involved in the excretion process in the human body?

kidneys, liver, and lungs

 Common CNS depressants  Causes disorientation, euphoria, and confusion

ALCOHOLS

“grain alcohol”

Ethanol

 Most common  Converted to Acetic acid – hangover is due to acetaldehyde (via alcohol dehydrogenase activity)  Fatal dose: 300-400 mL

Ethanol

Ethanol is converted to? Hangover is due to______ (via ____________ activity)

Acetic acid; acetaldehyde ; alcohol dehydrogenase

Fatal dose of Ethanol

300-400 mL

Stages of impairment by Ethanol

0.01 – 0.05- No obvious impairment, some changes observable during testing 0.03 – 0.12 -Mild euphoria, low inhibitions, some impairment of motor skills 0.09 – 0.25- Low inhibitions, loss critical judgement, memory impairment, low reaction time 0.18 – 0.30-Mental confusion, dizziness, strong impaired motor skills 0.27 – 0.40- Unable to stand and walk, vomiting, impaired consciousness 0.36 – 0.50 COMA and POSSIBLE DEATH

“Wood alcohol”

Methanol

-Common solvent, contaminant to homemade liquors -Converted to formaldehyde and then to formic acid in the liver -Fatal dose: 60-250 Ml

Methanol

Fatal Dose of Methanol

60-250 Ml

How is methanol metabolized in the body?

it is converted to formaldehyde and then to formic acid in the liver

“Rubbing alcohol”

Isopropanol

How is isopropanol metabolized in the body?

It is converted to acetone by hepatic alcohol dehydrogenase

Fatal Dose of Isopropanol

250 mL

 Colorless, Odorless, Tasteless  From gasoline, and cigarette smoke

CARBON MONOXIDE

-Few amounts are produced in the body from metabolism -With high affinity to hemoglobin that leads to carboxyhemoglobin formation and to tissue hypoxia

CARBON MONOXIDE

How is carbon monoxide poisoning identified and measured?

Indicator: Cherry red color of the face Method: Carboxyhemoglobin measurement

 Can be solid or gas  A super toxic substance in insecticides, rodenticides, pyrolysis products

CYANIDE

 Binds to iron-binding substances and may cause cellular hypoxia (fast acting)

CYANIDE

How is cyanide poisoning identified?

"Odor of Bitter Almonds"

HEAVY METALS

Arsenic Cadmium Lead

What are the symptoms associated with Cyanide

Tachypnea (rapid breathing) Convulsions Coma

They are toxic if ingested and absorbed by the body

Heavy Metals

common component of poisons, rodenticides, paints

ARSENIC

Arsenic  With high affinity to _____  Commonly used in ______  Inhibits ______  Toxicity is via _______  Can cross ______

-keratin -homicides, suicide agents, and heavy metal poisoning -sulfhydryl enzymes -binding to thiol groups in proteins -PLACENTA

METHOD IN ARSENIC

 Reinsch test  Atomic absorption spectrophotometry

-Soft, Bluish-white metal easily cut with a knife  A significant environmental pollutant  Acquired from ingestion of food stored in cadmium containers

Cadmium

MAIN SOURCE source of cadmium

Coal burning

Where does cadmium accumulates

renal tubules, liver, and muscles

How is cadmium toxicity indicated?

A positive (+) gamma-glutamyl transferase (GGT) in urine sample

Cadmium inhibits

type 1 epithelial cells of the lungs

components of household paints

Lead

 A potent enzyme inhibitors  Goes to the matrix of the bones and may persist for a long time  Blocks vitamin D and d-ALA

Lead

Causes "Wrist drop/Foot drop

Lead

Toxic dose of Lead

>0.5 mg/day

Indicators of Lead Toxicity

Increased urine ALA Increased free RBC protoporphyrin Basophilic stipplings

Method of Lead

 Inductively coupled plasma emission spectrophotometry  Zinc protoporphyrin

Specimen used in Lead

Whole blood – with greater sensitivity Note: Serum and Plasma is NOT ALLOWED Urine- for recent exposures

 Binds with proteins and is an environmental pollutant  Amalgamates with other substances  Small drops are highly dangerous in a poorly ventilated room  Affects glomerular integrity and accumulates in the CNS  Highly toxic in vapor form

MERCURY “Quicksilver”

“Quicksilver”

MERCURY

Mercury Detection Method

Reinsch Test

Specimen for Mercury

whole blood for organic mercury, and urine for inorganic mercury.

MERCURY HEALTH EFFECTS

 Skin burns  Irritation of nose and skin  Rashes  Excessive perspiration  Damage to the kidneys  Damage to vision  Dysfunctional of the central nervous system  Loss of hearing and muscle coordination  Severe brain damage  Death

overuse or consumption of drugs other than for medical reasons or more than recommended dose.

Drug Abuse

Compulsion to use a drug to experience psychological or physical effects despite any deterioration in health, work or social activity

Drug dependence

Almost all drugs are basic drugs with benzene rings (Acidic = barbiturates)

Drug dependence

Classification of Drugs

Natural Drugs Synthetic Drugs

Natural Drugs

Raw opium Marijuana Coca bush

Synthetic Drugs

- Methamphetamine - Barbiturates

Any drug that produces sleep or stupor and also relieves pain (Medical)

Narcotics

Depress the central nervous system to produce marked reduction in sensitivity to pain, create drowsiness and reduce physical activity

Narcotics

In large doses, may cause coma and/or convulsions

NARCOTICS

Psychotropic Drugs

 Drugs with inhibitory type of action  Drugs with exciting type of action

 Drugs with inhibitory type of action

1. Neuroleptics 2. Tranquilizers 3. Sedative drugs

 Drugs with exciting type of action

1. Psychostimulants 2. Antidepressants

 New psychoactive drugs that tend to be abused by teens and young adults at the bars, clubs and raves

Designer Drugs

Properties and effects are similar to hallucinogens or narcotics but have altered chemical structure

Designer Drugs

Designer Drugs EXAMPLE

 Ecstasy  Synthetic cannabinoids  Synthetic cathiones

DRUGS OF ABUSE

Amphetamines Anabolic steroids Phencyclidine Cannabinoids Cocaine Opiates Sedative Hypnotics

- for narcolepsy and attention deficit disorders

Amphetamines

 Increases mental alertness and physical capacity  Reduces appetite, relieves mental depression, comfort fatigue and sleepiness

Amphetamines

Amphetamines structurally related to

Dopamine and Catecholamines

(Popular designer drug)

Ecstasy

In Amphetamines Acute intoxication can lead to

hyperpyrexia

-One common type of amphetamine - is commonly known as

-"3,4 methylenedioxymethamphetamine," -"Ecstasy,"

Toxic effects of Amphetamines

 Restlessness  Coma  Hypertension  Cardiac arrhythmias  Convulsions  Pancytopenia  Death

Shabu

Methamphetamine HCL

white, odorless, and crystalline substance

Methamphetamine HCL - “Shabu”

Methamphetamine HCL - “Shabu” Route

 Ingestion  Inhalation  Injection  Snorting

“ecstasy”

3,4 methylene dioxide N Methylamphetamine

 White, yellow or brown in color  In capsule or in tablet

3,4 methylene dioxide N Methylamphetamine

3,4 methylene dioxide N Methylamphetamine Route

 Oral  Snorting

3,4 methylene dioxide N Methylamphetamine Effects

 Feeling of emotional closeness to others  Increased sociability  Exaggerated emotions  Rise in blood pressure

Amphetamine-like compounds:

 Ephedrine  Pseudoephedrine  Phenylpropanolamine

 White powder with numbing taste

Amphetamine sulfate

Effects of Amphetamine sulfate

1. Death 2. Cardiovascular anomalies 3. Jaundice 4. Microcephaly among babies

– Anabolic androgenic steroid

Anabolic steroids

 Associated with male hormone testosterone  Increases muscle mass (for athletes) – improves athletic performance

Anabolic steroids

Toxic effects of Anabolic steroids

 Chronic hepatitis  Atherosclerosis  Abnormal Platelet aggregation  Cardiomegaly

“Angel dust”, “Angel hair”

Phencyclidine

-Has hallucinogenic and anaesthetic properties, depressant effects  Ingested or inhaled  10-15% is unchanged and can be seen in urine

Phencyclidine

Major metabolite of Phencyclidine

Phencyclidine HCL

Phencyclidine toxic effects

 Stupor  Coma

“Marijuana”, “Mary Jane”, “Pampapogi” “Hashish”

Cannabinoids

most potent component

Tetrahydrocannabinol

Lipophilic, stays in adipose tissue (long time)

Tetrahydrocannabinol

Cannabinoid effects

Sense of well-being, Euphoria, Mood changes May include  Red conjunctiva  Tachycardia  Poor memory

Cannabinoids Detected in urine for ____ up to _____ after use

3-5 days up to 4 weeks

Urinary metabolite of Cannabinoids

“11 nor-deltatetrahydrocannabinol” (THC-COOH)

“Crack”

Cocaine

 An Alkaloid salt  One of the strongest and shortest acting stimulant that elicits a sense of excitement and euphoria -a local anesthetic in nasopharyngeal surgery

Cocaine

derived from the Coca plant (Erythroxylon) and is sometimes used as an additive in certain foods.

Cocaine

Coca plant

“Erythroxylon"

-Administered via inhalation or intravenous injection --Long-term effects include physical and mental deterioration, and violent behavior -Easily passed in placenta and breastfeeding -Can cause sudden death due to direct toxicity on myocardium

Cocaine

cocaine can be detected in urine up to _____ For chronic users?

3 days 20

urinary metabolite of cocaine is

“Benzoylecgonine”

 Capable of analgesia, Sedation, Anesthesia  Highly addictive  From Opium poppy

Opiates

 Natural:  Chemically modified:  Common synthetic opiates:

-Opium, Morphine, Codeine -Heroin, Hydromorphone, Oxycodone -Meperidine, Methadone, Propoxyphene, Pentazocine, Fentanyl

Opiates major metabolite

N-acetylmorphine (heroin) and Morphine

Opiates laboratory tests

Immunoassays

Opiate effects

 Acute overdose: Respiratory acidosis, Myoglobinuria  High overdose: Death due to cardiopulmonary failure

causes Respiratory depression

Sedative Hypnotics

2 categories of Sedative Hypnotics

Barbiturates Benzodiazepines

Barbiturates

 Pentobarbital  Secobarbital  Phenobarbital

Benzodiazepines

 Chlordiazepoxide  Lorazepam  Diazepam

Drug Testing Specimen:

1. Blood – for currently circulating drug, or alcohol 2. Urine – to check drug metabolites 3. Serum – currently circulating drug 4. Hair – low levels but with longer positivity 5. Exhaled breath – for alcohol testing 6. Sweat – check parent drug 7. Saliva – check for free or active form of the drug

Drug testing (confirmatory) Methods:

1. Thin layer chromatography 2. Liquid chromatography 3. HPLC 4. Gas chromatography

Cannabinoids knows as

“Marijuana”, “Mary Jane”, “Pampapogi” “Hashish”