[M8] Part 1: Toxicology Flashcards
Study of poisons
TOXICOLOGY
substances that cause harmful effect upon exposure
Poisons
According to bishop, toxicology is the study of ____
xenobiotics
substances that are not normally found or produced by the body
Xenobiotics
WHAT ARE THE 4 MAJOR DISCIPLINES OF TOXICOLOGY
Mechanistic Toxicology
Descriptive Toxicology
Forensic Toxicology
Clinical Toxicology
Studies the dose-response mechanism of toxins
Mechanistic Toxicology
dose of toxin
that will cause in harmful effects
Dose-response mechanism
Mechanistic toxicology elucidates the ___, ____, and ____ effects of toxins based on a given dose
cellular
molecular
biochemical
Provides a basis for rational therapy design
Mechanistic Toxicology
Development of laboratory tests to assess the
degree of exposure in individuals
Mechanistic Toxicology
Risk assessment of toxins and/or therapeutic drugs that may elicit toxic effects
Descriptive Toxicology
a part of pre-clinical studies
for novel drugs (new drugs, therapeutic
methods, vaccines)
Risk assessment
It assesses the effective, toxic, and lethal dose
Risk assessment (descriptive toxicology)
Risk assessment is performed by the ____
food and
drug administration
Uses result from animal experiments to predict what
level of exposure will cause harm in humans
Descriptive Toxicology
T/F: Dose harmful to animals may sometimes be
harmful to humans as well
T
Medical and legal consequences of exposure to toxins
Forensic Toxicology
Give an Example of Forensic Toxicology
autopsy
Establishes and validates analytical performance of
tests methods used to generate evidence in legal situations
Forensic Toxicology
Study of interrelationship between toxin exposure and disease states
Clinical Toxicology
Emphasis on diagnostic testing and therapeutic intervention (antidote for specific toxins)
Clinical Toxicology
What are the ROUTES OF EXPOSURE in toxicology
- Ingestion
- Inhalation
- Transdermal absorption
most often observed route of exposure in clinical setting
inhalation
ABSORPTION in toxicology
Gastrointestinal tract
T/F: Gastrointestinal tract utilizes ACTIVE diffusion
F; passive diffusion
readily diffusible across cell membranes
Hydrophobic substance
Hydrophobic substance: polar or non-polar?
non-polar
cannot passively diffuse across cell membranes
Ionized substance
Ionized substance requires ___
transporters
Weak acids – absorbed in the___
stomach
Weak bases – absorbed in the___
intestine
T/F: There are toxins that are not absorbed by the GI tract
T
There are toxins that are not absorbed by the GI tract. These toxins produce ___
local effects
What are the 4 factors under absorption
- Rate of dissolution
- Gastrointestinal mobility
- Resistance to degradation
- Interaction with other substances
The rate of diffusion is dependent on the ___ of ___ in the ___
dissolution
toxins
GI tract
In Gastrointestinal mobility,
Low bowel movement, diarrhea = ___ (more/less) absorption
less
Toxins that are resistant to degradation may or may not be ___ by the ___
absorbed
GI tract
Interaction of toxins with other substances present in the GI tract may cause ____ (inc/dec) in the ___ of ___
decrease
rate
absorption
single, short-term exposure to a substance
Acute toxicity
repeated exposure for extended period of time
Chronic toxicity
dose that would predict to produce a toxic response in 50% of the population
TD50
dose that would predict death in 50% of the population
LD50
dose that would be predicted to be effective or have a therapeutic benefit in 50% of the population
ED50
Toxic agents are analyzed through:
screening test
confirmatory test
Rapid, simple, qualitative procedure intended to detect the presence of specific substance
Screening Test
Screening test:
Good ___, lack ___
sensitivity
specificity
Quantitative analysis of toxic agents
Confirmatory test
Confirmatory Test is Specific for a ___ or ___
single substance
class
What are the methods used in the analysis of toxic agents
● Three-layer chromatography (TLC)
● Gas chromatography (GC)
● ICP-MS/AA
● GC-MS
ICP-MS/AA standa for:
Inductively coupled plasma-mass spectrometry/atomic absorption
Used for inorganic substances
ICP-MS/AA
GC-MS stands for:
Gas chromatography-mass spectrometry
Reference method
GC-MS
Used for organic substances
GC-MS
Common CNS depressant
Alcohol
Low dose exposure to alcohol will cause:
disorientation, confusion,
euphoria
High dose exposure to alcohol will cause:
unconsciousness, paralysis,
death
What are the 4 types of alcohol
ethanol
methanol
isopropanol
ethylene glycol
Ethanol is aka __
grain alcohol
Most common toxicant and substance of abuse (US)
ethanol
Depresses CNS and increases heart rate and blood pressure
ethanol
ethanol Depresses ___ and ____ heart rate and ___
CNS
increases
blood pressure
Vasopressin inhibitor
Ethanol
ethanol is a vasopressin inhibitor. It may cause ___ (dec/inc) urine output causing ___
increased
diuresis
Intoxication with alcohol will cause
blurred vision, incoordination, slurred speech, and coma, “hangover symptoms”
What is the antidote used in case of intoxication with ethanol
diazepam
what is the Fatal dose: of ethanol
300 – 400 mL (pure alcohol) ingested in < 1 hour
fatal dose of ethanol:
___-___ (pure ___) ingested in ____
300 – 400 mL
alcohol
< 1 hour
Toxic blood level of ethanol
> 400 mg/dL
The toxic blood level or ethanol is 400 mg/dL. If it reaches ___, patient is required to
undergo ___ to filter out the ___
and prevent ___
> 500 mg/dL
hemodialysis
alcohol
intoxication
Method of analysis in ethanol
enzymatic (alcohol
dehydrogenase)
STAGES OF IMPAIRMENT BY ALCOHOL:
What is the blood ethanol level if there is No obvious impairment
0.01 – 0.05 %, w/v
STAGES OF IMPAIRMENT BY ALCOHOL:
What is the blood ethanol level if there are Mild euphoria, decrease inhibitions, some impairment of motor skills
0.03 – 0.12 %, w/v
STAGES OF IMPAIRMENT BY ALCOHOL:
What is the blood ethanol level if there are Decrease inhibitions, loss of critical judgment, memory impairment, diminished reaction time
0.09 – 0.25 %, w/v
STAGES OF IMPAIRMENT BY ALCOHOL:
What is the blood ethanol level if there are Mental confusion, dizziness, strongly impaired motor skills (staggering, slurred speech)
0.18 – 0.30 %, w/v
STAGES OF IMPAIRMENT BY ALCOHOL:
What is the blood ethanol level if there are Inability to stand or walk, vomiting, impaired consciousness
0.27 – 0.40 %, w/v
STAGES OF IMPAIRMENT BY ALCOHOL:
Sign and symptoms: Coma and possible death
Blood Ethanol Level?
0.36 – 0.50 %, w/v
Methanol is aka
wood alcohol
aka wood alcohol
methanol
Most commonly used solvent
methanol
Contaminant of homemade liquors
methanol
Methanol is Metabolized to ___ and then to ___
in the ___
formaldehyde
formic acid
liver
causes intoxication
Formic acid
T/F: Ethanol intoxication is more severe than methanol intoxication
F; Methanol intoxication is more severe than ethanol intoxication
Methanol Intoxication will result in:
metabolic acidosis, pancreatic
necrosis, and ocular toxicity
ocular toxicity is aka
frank blindness
Antidote for methanol intoxication
sodium bicarbonate
Methanol fatal dose
60 – 250 mL
Methanol Toxic blood level:
> 50 mg/dL
Isopropanol is aka
rubbing alcohol
aka rubbing alcohol
Isopropanol
Commonly available form of alcohol
Isopropanol
Isopropanol is Metabolized to ____ by ___
acetone
hepatic ADH
Isopropanol is CNS ___
depressant
Toxicity is similar to ethanol toxicity
Isopropanol
Intoxication lasts longer than ethanol because of acetone
Isopropanol
Isopropanol Intoxication lasts longer than ethanol because of ___
acetone
has a longer half-life in the body compared to the metabolites of ethanol
acetone
Antidote for isopropanol Intoxication
activated charcoal
Isopropanol Fatal dose:
250 mL
Ethylene Glycol is aka
1,2-ethanediol
aka 1,2-ethanediol
Ethylene Glycol
Component of hydraulic fluid and anti-freeze
Ethylene Glycol
If Accidentally ingested by children, has a naturally sweet taste
Ethylene Glycol
Ethylene Glycol is Metabolized to ___ and ___
→ May cause ______
oxalic acid
glycolic acid
severe metabolic acidosis
Ingestion of high levels of Ethylene Glycol will cause deposition of ___ crystals in ___ causing ___
calcium oxalate
renal tubules
kidney damage
What are the sample used for the determination of alcohol
whole blood, serum, plasma
In Ethanol determination:
Capped at all times to prevent ___
alcohol evaporation
In Ethanol determination:
Use of _____ antiseptic
alcohol-free
Why is alcohol-free antiseptic used in ethanol determination?
because Alcohol-based antiseptics may
contaminate the sample and cause false increase
Alcohol-based antiseptics may
___ the sample and cause false ___ (inc/dec)
contaminate
increase
Ethanol determination:
Uses ___, which Prevent___ and ____
contamination. It may also produce alcohol as their ___ and cause false ___
fluoride tubes
glycolysis
bacterial
byproduct
increase
In ethanol determination:
Serum and/or plasma has ___ (higher/lower) ethanol concentration than ___
higher
whole blood
T/F: Ethanol is NOT uniformly distributed in body water such as serum and plasma
F; Ethanol is uniformly distributed in body water
such as serum and plasma
What are the methods used for the determination of alcohol
Enzymatic method
Gas Chromatography
Osmometry methods
Utilizes alcohol dehydrogenase
for ethanol determination
enzymatic method
Enzymatic method Utilizes ____ for ethanol determination
alcohol dehydrogenase
Reference method for ethanol determination
Gas Chromatography
may also be used to quantitate methanol and isopropanol
Gas Chromatography
Computed method
Osmometry methods
Osmometry methods or
osmolal gap
what is the formula for osmometry method (osmolal gap)
● 𝑜𝑠𝑚𝑜𝑙𝑎𝑙 𝑔𝑎𝑝 = 𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 − 𝑐𝑎𝑙𝑐𝑢𝑙𝑎𝑡𝑒𝑑 𝑜𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦
In Osmometry methods (osmolal gap),
___ mOsm/Kg = ___serum ___
↑ 10
60 mg/dL
ethanol
T/F Osmometry methods (osmolal gap) is specific to ethanol
F; NOT specific to ethanol
T/F: Osmometry methods (osmolal gap) is NOT specific to ethanol as it May also increase in other conditions
T
Produced by incomplete combustion of carbon containing substances
CARBON MONOXIDE (CO)
Colorless, odorless, and tasteless gas that is rapidly absorbed into the blood
CARBON MONOXIDE (CO)
CARBON MONOXIDE (CO) Has ___ more affinity to ___ than ___
200x – 225x
hemoglobin
oxygen
Carbon monoxide has 200x – 225x more affinity to hemoglobin than oxygen, resulting to ____ formation giving a ___ blood
carboxyhemoglobin
cherry red-colored
carboxyhemoglobin formation may: (2)
✓ May result to ___
✓ Affects ___ and ___
hypoxia
heart
brain
Treatment for carbon monoxide
100% oxygen therapy
Symptoms of ____ depends on the concentration of ___ in the blood
Carboxyhemoglobinemia
carboxyhemoglobin
CARBON MONOXIDE (CO):
Signs and Symptoms: Typical in non-smoker
Carboxyhemoglobin (%): ___
0.5
CARBON MONOXIDE (CO):
Signs and Symptoms: Range of values seen in smokers
Carboxyhemoglobin (%): ___
5 – 15
CARBON MONOXIDE (CO):
Signs and Symptoms: Shortness of breath with vigorous exercise
Carboxyhemoglobin (%): ___
10
CARBON MONOXIDE (CO):
Signs and Symptoms: Shortness of breath with moderate exercise
Carboxyhemoglobin (%): ___
20
CARBON MONOXIDE (CO):
Signs and Symptoms: Severe headache, fatigue, impairment of judgment
Carboxyhemoglobin (%): ___
30
CARBON MONOXIDE (CO):
Signs and Symptoms: Confusion, fainting on exertion
Carboxyhemoglobin (%): ___
40-50
CARBON MONOXIDE (CO):
Signs and Symptoms: Unconsciousness, respiratory failure, death with continuous exposure
Carboxyhemoglobin (%): ___
60-70
CARBON MONOXIDE (CO):
Signs and Symptoms: Immediately fatal
Carboxyhemoglobin (%): ___
80
What are the Methods for Determining Carboxyhemoglobin in the Blood
Spot Plate Test
Differential Spectrophotometry
Gas Chromatography
In Spot Plate Test
● Dilute ___ with ___
→ ___ part of blood per ___ parts volume of solution
blood
water
1
20
In spot plate test
5mL of 40% ___ + 5mL aqueous ___ (1/20)
NaOH
whole blood
In Spot Plate Test:
Observe formation of ___ color in solution
pink
In Spot Plate Test:
Pink color = ___
> 20% COHb
what method has this principle?
different forms of hemoglobin present with different spectral absorbency curves
Differential Spectrophotometry
how many wavelengths are used in Differential Spectrophotometry
6 different wavelengths
Most commonly used method and basis of automated systems
Differential Spectrophotometry
An accurate and precise method for Determining Carboxyhemoglobin in the Blood
Gas Chromatography
Reference method for Determining Carboxyhemoglobin in the Blood
Gas Chromatography
What method has this principle?
utilizes thermal conductivity by releasing
carbon monoxide using potassium ferricyanide
Gas Chromatography
Gas Chromatography utilizes ___ by releasing
carbon monoxide using ___
thermal conductivity
potassium ferricyanide
Found in many household products and occupational settings
CAUSTIC AGENTS
Caustic agents:
Exposure: ___ or ___
aspiration or ingestion
causes pulmonary edema and
shock. Can lead to death
Aspiration
cause lesions to the esophagus
and GIT (perforation)
Ingestion
May lead to hematemesis, abdominal pain
and shock, and metabolic acidosis or
alkalosis
Ingestion of CAUSTIC AGENTS
Ingestion of CAUSTIC AGENTS May lead to ___, ___
and ___, and___ or ___
hematemesis
abdominal pain
shock
metabolic acidosis
alkalosis
Antidote for CAUSTIC AGENTS
dilution
Super toxic substance
CYANIDE
CYANIDE may exist as ___ or ___
solid or gas
form of cyanide that has a bitter almond odor
gas form
Used in many industrial processes
CYANIDE
Component of insecticides and rodenticides
CYANIDE
CYANIDE is Produced by ____ of some ___
pyrolysis
plastics
decomposition or degradation at high temperature
Pyrolysis
One of the most common suicidal agents in the form of silver cleaners
CYANIDE
route of exposure for cyanide
inhalation, ingestion, transdermal absorption
exposure to both cyanide and carbon monoxide
Smoke inhalation
CYANIDE:
Toxicity: binds to ____ and ______
heme iron;
mitochondrial cytochrome oxidase
If cyanide binds to ____, hemoglobin will not be able to bind with ___ and may cause ___ and ___
heme iron
oxygen
hypoxia
anemia
CYANIDE:
If Mitochondrial cytochrome oxidase is ___, it may ___ (inc/dec) ____ and ___
inhibited
increase
cellular oxygen tension
venous partial oxygen pressure
What are the methods in cyanide
Ion-selective electrode
Photometric assay
Urinary thiocyanate concentration
most commonly used cyanide methods
Ion-selective electrode & Photometric assay
Photometric assay is aka
two-well microdiffusion separation
this method is only used when exposed to very low levels of cyanide
Urinary thiocyanate concentration
what are the different metals and metalloids
Arsenic
Cadmium
Lead
Mercury
Pesticides
A metalloid that exists as a bound to or as a primary constituent of many organic or inorganic compounds
Arsenic
Arsenic Has ___ and binds to ___ groups in ___
high affinity
thiol
protein
Common homicidal and suicidal agent
Arsenic
Has the capacity to cross the placenta
arsenic
Arsenic Intoxication will result to:
intravascular hemolysis, hemoglobinemia, nephrotoxicity, and multi-organ involvement
what is the Indication of arsenic intoxication
garlic odor breath and
metallic taste
Specimen used for SHORT TERM exposure to arsenic
Blood, urine
Specimen used for LONG TERM exposure to arsenic
Hairs, nail
Arsenic loves to bind to ___
keratinized tissues
Methods in arsenic
AAS, Reinsch test
Utilized in electroplating and galvanizing
Cadmium
Found in paints and plastics
Cadmium
Binds to proteins and cellular constituents
Cadmium
Cadmium Binds to ___ and ___ constituents
proteins
cellular
Cadmium Toxicity is ___
nephrotoxic
Cadmium toxicity is nephrotoxic Such as ____, ___, and ___
tubular proteinuria
glucosuria
aminoaciduria
Cadmium:
Specimen: ___
urine, whole blood
Cadmium:
Method: ___
AAS
Color enhancer in paints and make-ups
Lead
Also found in gasoline and pipe plumbing
Lead
Common water contamination
Lead
A potent enzyme inhibitor
→ ____, ____, ____
LEAD
D-ALA synthetase
pyrimidine-5’-nucleotidase
Na-K ATPase
Has high affinity to many macromolecular structures and distributed throughout the body
Lead
___ is present in all biologic systems,
however, it has no ___ or ___
function
Lead
physiologic
biochemical
Elimination of LEAD is through ____
renal filtration
Elimination through renal filtration
LEAD
Elimination is very slow dahil mababa ang concentration in the blood
LEAD
It combines with the bone matrix
LEAD
Largest pool of lead in the body is in the ____
skeletal system
May persist for a long period of time (up to ____)
LEAD
20 years
Lead Toxicity:
Toxic dose: ___
> 0.5 mg/day
Lead Toxicity:
Fatal dose: ___
0.5g
Lead Toxicity:
Toxic blood levels: ____
> 70 ug/dL
Indications of LEAD TOXICITY
Basophilic stippling of RBC
Increased urinary ALA
Free RBC protoporphyrin
Lead inhibits ____
pyrimidine-5’-nucleotidase
Responsible for removing excess DNA in RBC nucleus
pyrimidine-5’-nucleotidase
Indications of Lead toxicity:
In Basophilic stippling of RBC, ___ accumulates inside the ___ causing the ____ (____)
DNA
RBC
blueberry muffin-like RBC
basophilic stippling
Presence of basophilic stippling is a sensitive indicator of ____
lead poisoning
Presence of ___ is a sensitive indicator of lead poisoning
basophilic stippling
What is the Treatment for lead toxicity
chelators
give the 2 examples of chelators used as a treatment for lead toxicity
EDTA, dimercaptosuccinic acid
What are the Toxic effects of lead toxicity (3)
→ Anemia
→ Decreased RBC membrane integrity
→ Encephalopathy, nephrosis, anorexia, peripheral neuropathy, birth defects, low IQ,
carcinogenesis, birth defects, renal damage
Among the toxic effects of lead toxicity, what Inhibits heme synthesis?
Anemia
LEAD:
Specimen: ____
whole blood, urine, hair
specimen used in analysis of lead that is used to quantitate lead (it is bound to RBC)
Whole blood
specimen used in the analysis of lead that is used when there is recent lead
exposure
urine
What are the SCREENING METHODS used in the analysis of LEAD
Zinc Protoporphyrin test
ALA dehydratase (ALAD test)
Zinc Protoporphyrin test is aka
Fluorometric test
sensitive SCREENING method used in the analysis of LEAD
ALA dehydratase (ALAD test)
Lead inhibits delta-ALA synthetase = ___ (inc/dec) in ALA activity = suggestive of ____
decrease
lead poisoning
What are the OTHER METHODS used in the analysis of LEAD
→ In-vivo X-ray fluorescence of bone
→ AAS
→ ICP-MS
→ Anodic stippling voltammetry
Exists in three forms which has different levels of toxicity
Mercury
What are the 3 forms of MERCURY
Elemental mercury
Inorganic salts
Component of organic compounds
form of mercury that is Liquid at room temperature
Elemental mercury
form of mercury that Can be ingested and show no significant effects
Elemental mercury
form of mercury that Cannot be absorbed
Elemental mercury
in this form of mercury, Inhalation is very rare and insignificant
Elemental mercury
Moderately toxic form of mercury
Inorganic salts
form of mercury that is Partially absorbed by the GIT
Inorganic salts
T/F Yung mga hindi naabsorb na Inorganic salt (form of mercury) may show GIT toxicity
T
Most toxic form of mercury
Component of organic compounds
form of mercury that is Rapidly absorbed
Component of organic compounds
Mercury is a potent enzyme __.
For example: ____
inhibitor
Catecholamine-0-methyltransferase
What enzyme Metabolizes catecholamines
Catecholamine-metabolic enzyme
example of catecholamines
epinephrine and norepinephrine
If the catecholamines are not ___, it may lead to ___
metabolized
toxicity
The toxicity of this metal/metalloids Mimics adrenal gland disorders
mercury
what are the indicators of mercury toxicity
hypertension, tachycardia, sweating
the indicators of mercury toxicity is the Symptoms of ___
pheochromocytoma
tumor
that autonomously produces catecholamines
Pheochromocytoma
what are the three mercury Intoxication
Elemental mercury
Alkyl mercury
Inorganic form
mercury intoxication:
pink disease (acrodynia), erethism
Elemental mercury
pink disease is aka
acrodynia
Upon exposure, it may cause continuous
skin exfoliation until the skin turns pink
(acrodynia)
Elemental mercury
congenital minimata disease
Alkyl mercury
neurologic disorder that resembles cerebral palsy
Congenital minimata disease
Congenital minimata disease is a neurologic disorder that resembles ___
cerebral palsy
nephrotoxic (glomerular proteinuria)
Inorganic form
What are the specimen used in the analysis of mercury
whole blood, 24-hour urine
What are the methods used in the analysis of mercury
→ Reinsch test
→ AAS
→ Anodic stippling voltammetry
MERCURY:
Reference Value: ___
<10 ug/dL
Mercury:
Significant exposure: ___ (____)
> 50 ug/dL
whole blood
Substances intentionally added to the environment to kill or harm undesirable life forms
Pesticides
Pesticides is Classified as ___ or ___
insecticides
herbicides
What are the 3 Forms of insecticides:
Organophosphate
Carbamates
Halogenated Hydrocarbons
most common form of insecticides
Organophosphate
Responsible for about 1⁄3 of all pesticide poisoning
Organophosphate
Organophosphate is Responsible for about ___ of all ___
1⁄3
pesticide poisoning
Organophosphate Inhibits the enzyme ____
acetylcholinesterase
Acetylcholine is Metabolized by ____
acetylcholinesterase
Muscle cell stimulant
Acetylcholine
Also the stimulant of some
exocrine and endocrine glands
Acetylcholine
T/F When acetylcholinesterase is inhibited, acetylcholine is metabolized
F; When acetylcholinesterase is inhibited, acetylcholine is NOT metabolized
When acetylcholinesterase is inhibited, acetylcholine is NOT
metabolized which may cause ____.
systemic effects
Carbamates Inhibits the enzyme ___
acetylcholinesterase
what are the 2 forms of insecticides that inhibit acetylcholinesterase
Organophosphate
Carbamates
Toxicity (Pesticides)
Low-level exposure: (4)
Salivation, Lacrimation, Involuntary urination and defecation
Toxicity (Pesticides)
High-level exposure: (7)
Bradycardia, muscular twitching, cramps, apathy, slurred speech, behavioral changes, death
high level exposure pesticides may cause death which happens due to___
respiratory failure
Direct measurement of organophosphates is ____
highly impossible
Direct measurement of organophosphates is highly impossible because Organophosphate has ____ to ___
high affinity
proteins
Pesticides:
Method of analysis: ____
indirect measurement.
what are the 2 methods used in the analysis of pesticides
Acetylcholinesterase Inhibition Assay
Serum Pseudocholinesterase Activity
Indirect measurement of organophosphate poisoning
Acetylcholinesterase Inhibition Assay
Specimen used in Acetylcholinesterase Inhibition Assay
RBC
Alternative and Screening test for pesticides
Serum Pseudocholinesterase Activity
T/F: Serum Pseudocholinesterase Activity lacks sensitivity and specificity.
T
Serum Pseudocholinesterase Activity is decreased in ___, ____, ____, ____
acute infection, pulmonary embolism, hepatitis, cirrhosis
Decreased also in acute infection, pulmonary embolism, hepatitis, cirrhosis
Serum Pseudocholinesterase Activity
