Toxicology

Front 1

Exposure to toxins

Back 1

1.) Intensional (suicide, accident)
2.) Homicide
3.) Occupational exposure

Front 2

Exposure routes

Back 2

1.) Ingestion - most common, hydrophobic substances simply diffuse across membrane, weak acids are absorbed by stomach, weak bases absorbed small intestine
2.) Inhalation
3.) Transdermal

Front 3

Symptoms of drug overdose

Back 3

- awake, unable to speak
- body is limp
- pale
- slow or erratic heartbeat
- vomitting
- choking sounds, gurgling
- shallow breathing, no breathing

Front 4

Comprehensive Drug Analysis

Back 4

- serum (most common, no additive)
- suspected overdose
- toxicology labs, Gas Chromatography/Mass Spectroscopy, HPLC

Front 5

Drugs in urine screen

Back 5

1.) Tetrahydrocannibinol (THC)
2.) Amphetamines and methamphentamine
3.) Opiates
4.) Barbiturates
5.) Benzodiazepines
6.) Cocaine
7.) Phencyclidine (PCP)

Front 6

Tetrahydrocannibinol

Back 6

- urine drug screen
- metabolite: THC-COOH
- half-life depends on user status: few days to 4 weeks

Front 7

Amphetamines (and methamphetamine)

Back 7

stimulants

Front 8

Opiates

Back 8

- opium, morphine, codeine
- acute overdose: respiratory center depression and cardiopulmonary failure
- false positive w/ poppy seeds

Front 9

Barbituates

Back 9

sedative hypnotic

Front 10

Benzodiazepines

Back 10

sedative hypnotic

Front 11

Cocaine

Back 11

- local anesthetic
- a CNS stimulator
- brief half-life, 0.5-1 hour

Front 12

Phencyclidine (PCP)

Back 12

- hallucinogen with stimulant, depressant, and anesthetic properties
- may be detected 7-30 day after last exposure

Front 13

Urine drug screen

Back 13

- THC, Amphetamines, Opiates, Barbituates, Benzodiazepine, Cocaine, and Phencyclidine
- Immunoassay: screening test reported as a qualitative result (positive or negative)
: confirmatory test by GC/MS
- designed to detect a specific substance or a class of substances

Front 14

Acute Toxicity

Back 14

consequence of single short term exposure

Front 15

Chronic Toxicity

Back 15

repeated frequent exposure over long period of time

Front 16

Dose-response relationship

Back 16

- comparison of responses of a therapeutic drug over a range of doses
- cumulative response (%) vs. oral dosage

Front 17

ED50

Back 17

the dose of drug in which 50% of treated individuals will experience benefits

Front 18

TD50

Back 18

the dose of drug in which 50% of individuals will experience toxic adverse effects

Front 19

LD50

Back 19

the dose of drug in which 50% of individuals will result in mortality

Front 20

Alcohol

Back 20

1.) Ethanol (EtOH)
2.) Isopropanol
3.) Methanol
4.) Ethylene glycol
- detected by gas chromatography

Front 21

Ethanol (EtOH)

Back 21

- CNS depressant
- Symptoms: disorientation, confusion, unconsciousness, coma, death
- Metabolism: hepatic
- Specimen: don't use alcohol to clean arm, keep capped
- Analysis: enzymatic, ADH reaction, measure ABS 340nm
- Serum osmolality increases ~10 mOsm/kg for each 60 mg/dl increase in EtOH

Front 22

Primary detoxification pathway of ethanol

Back 22

- EtOH-->acetaldehyde by alcohol dehydrogenase
- NAD-->NADH ABS @340nm

Front 23

Isopropanol

Back 23

- Symptoms similar to EtOH
- not cleared as rapidly

Front 24

Methanol

Back 24

- formaldehyde-->formic acid-->acidosis-->death

Front 25

Ethylene glycol

Back 25

- sweet
- oxalic acid + glycolic acid
- renal stones
- acidosis

Front 26

Acetaminophen

Back 26

- analgesic, antipyretic, pain reliever
- therapeutic 10-30mg/mL
- toxic: >200mg/mL

Front 27

acetaminophen metabolism

Back 27

Normally involves formation of a glutathione conjugate which is excreted

Front 28

toxicity in an overdose for acetaminophen

Back 28

- liver glutathione is depleted
- toxic metabolic byproducts of acetaminophen increase in concentration
- The most toxic by-product is NAPQI

Front 29

N-acetyl-p-benzoquinoneimine (NAPQI)

Back 29

increased to a greater extent if acetaminophen toxicity occurs in the presence of alcohol or in individuals with chronic alcoholism

Front 30

Severe Hepatotoxicity

Back 30

increased AST & ALT in 3-5 days following overdose

Front 31

Acetaminophen assay

Back 31

Immunoassay or colorimetric methods

Front 32

Rumack-Matthew Nomogram

Back 32

- prediction of acetaminophen-induced hepatic damage based on serum concentration
- acetaminophen in plasma vs. hours after ingestion
- potentially rule out liver damage by reading graph
- 2 lines because of different methods, ref ranges

Front 33

Salicylate (acetylsalicylic acid

Back 33

- analgesic, anti-pyretic, anti-inflammatory, aspirin
- Therapeutic: < 100 mg/ml
- Toxic: > 150 mg/ml

Front 34

Salicylate (acetylsalicylic acid) toxic effects

Back 34

- Stimulates respiratory center, respiratory alkalosis, hyperventilation dec CO2
- Stimulates free fatty acid mobilization
- Inhibits TCA cycle
- Acidity of drug itself

Front 35

Salicylate (acetylsalicylic acid) method

Back 35

- Immunoassay
- Classic Trinder reaction: reaction with ferric nitrate-->purple chromogen

Front 36

Lead

Back 36

- Environmental contaminant
- Reference: Child: < 25 ug/dl, Adult < 40 ug/dl

Front 37

Lead toxicity

Back 37

- Alters protein structure & function

Front 38

Lead specimen

Back 38

- EDTA whole blood
- Atomic absorption
- Anode stripping: sample in present of electrical current deposits lead on electrode
- When current is reversed, Pb is oxidized: Pb-->Pb+2 + 2 e-

Front 39

Lead treatment

Back 39

- Chelating agents: EDTA, DMSA (ethylenediaminetetraacetic acid) and (dimercaptosuccinic acid)

Front 40

Protoporphyrin

Back 40

- Free erythrocyte protoporphyrin
- Zinc protoporphyrin
- Present in erythrocytes
- both may be used to screen for lead poisoning in children

Front 41

Mercury

Back 41

- Elemental: Hg, very low toxicity
- Cationic: Hg2+, moderate toxicity
- Organic: CH3Hg+, very toxic, hydrophobic body compartments
- brain and peripheral nerves
- Toxicity due to protein binding: tremors, behavioral changes, HTN, renal dysfunction, death

Front 42

Pesticides

Back 42

- Goal: target species specific but most pesticides exhibit nonselectivity
- Organophosphates and Carbamates

Front 43

Pesticides mechanism of action

Back 43

- cholinesterase inhibitors (acetylcholinesterase, AChE)
- Pesticide binds to AChE

Front 44

Pesticides low level exposure

Back 44

salivation, lacrimation,
involuntary urination, defecation

Front 45

Pesticides high level exposure

Back 45

- bradycardia, muscular twitching, cramps, slurred speech, and behavioral changes
- Death: Respiratory failure

Front 46

Serum pseudocholinesterase screen

Back 46

- If reduced pseudocholinesterase, administer antidote
- This pseudocholinesterase is nonspecific for carbamate and organophosphate exposure
- Also decreased in infections, liver disease and genetic SPChE variants
- confirmatory test: RBC cholinesterase

Front 47

Presence of AChE inhibitor

Back 47

produces colinergic stimulation which leads to symptoms of toxicity

Front 48

Pesticide antidote

Back 48

atropine: reverses organophosphate binding to AChE

Front 49

Arsenic

Back 49

- Source: industrial pollutant of air & water
- Toxicity: binds to –SH of proteins
- Chronic exposure: accumulation in tissues
- Quantitation: Atomic absorption

Front 50

Carbon monoxide

Back 50

Preferentially binds to Fe++ of Hb

Front 51

Cyanide

Back 51

- Exposure: industry, insecticides, burning plastic
- Exposure route: inhalation

Front 52

cyanide mechanism of action

Back 52

- binds to mitochrondial cytochrome oxidase
- uncouples oxidative phosphorylation
- rapid depletion of ATP

Front 53

cyanide detection

Back 53

- ISE used for detection in blood
- Methods to detect urinary thiocyanate when low level low level exposure is suspected

Front 54

Compound A is reported to have an oral LD50 of 5 mg/kg body weight. Compound B is reported to have an LD50 of 50 mg/kg body weight. Of the following statements regarding the relative toxicity of these two compounds, which is TRUE?
A.) Ingestion of low amounts of compound A would be predicted to cause more deaths than an equal dose of compound B
B.) Ingestion of compound B would be expected to produce no toxic effects at a dose of greater than 100 mg/kg body weight
C.) neither A nor B is toxic at any level or oral exposure
D.) A is more rapidly adsorbed from the GI tract than B
E.) B would be predicted to be more toxic than A if the exposure route were transdermal

Back 54

A.) Ingestion of low amounts of A would be predicted to cause more deaths than an equal dose of B

Front 55

Which of the following statements best describes the TD50 of a compound?
A.) The dosage of a substance that is lethal to 50% of the population
B.) The dosage of a substance that would produce therapeutic benefit in 50% of the population
C.) The dosage of a substance that would be predicted to cause a toxic effect in 50% of the population
D.) The percentage of individuals who would experience a toxic response at 50% of the lethal dose
E.) The percentage of the population who would experience a toxic response after an oral dosage of 50 mg

Back 55

C.) The dosage of a substance that would be predicted to cause a toxic effect in 50% of the population

Front 56

Of the following analytic methods, which is most commonly used as the confirmatory method for identification of drugs of abuse?
A.) Scanning differential colorimetry
B.) Ion-specific electrode
C.) Gas chromatography with mass spectrometry
D.) Immunoassay
E.) Nephelometry

Back 56

C.) Gas chromatography with mass spectrometry

Front 57

A weakly acidic toxin (pK=4.0) that is ingested will:
A.) not be absorbed because it is ionized
B.) not be absorbed unless a specific transporter is present
C.) be passively absorbed in the colon (pH=7.5)
D.) be passively absorbed in the stomach (pH=3.0)
E.) be absorbed only if a weak base is ingested at the same time

Back 57

D.) be passively absorbed in the stomach (pH=3.0)

Front 58

What is the primary product of methanol metabolism by the alcohol-aldehyde dehydrogenase system?
A.) acetone
B.) acetaldehyde
C.) oxalic acid
D.) formaldehyde
E.) formic acid

Back 58

E.) formic acid

Front 59

Which of the following statements concerning cyanide toxicity is/are TRUE?
A.) Inhalation of smoke from burning plastic is a common cause of cyanide exposure
B.) Cyanide is relatively nontoxic compound that requires chronic exposure to produce a toxic effect
C.) Cyanide expresses its toxicity by inhibition of oxidative phosphorylation
D.) all are true
E.) A and C are true

Back 59

E.) burning plastic and inhibition are true

Front 60

Which of the following laboratory results would be consistent with acute high-level oral exposure to an inorganic form of mercury (Hg2+)?
A.) High concentrations of mercury in whole blood and urine
B.) Proteinuria
C.) Positive occult blood in stool
D.) all are true
E.) all are false

Back 60

D.) all are true

Front 61

A child presents with microcytic, hypochromia anemia. The doctor suspects iron-deficiency anemia. Further laboratory testing reveals a normal total serum iron and iron-binding capacity; however, the zinc protoporphyrin level was very high. A urinary screen for prophyrins was positive. Erythrocytic basophilic stippling was noted on the peripheral smear. Which of the following laboratory tests would be best applied to this case?
A.) Urinary thicyanate
B.) Carboxyhemoglobin
C.) Whole blood lead
D.) Urinary anabolic steroids
E.) Urinary benzoylecgonine

Back 61

C.) whole blood lead

Front 62

A patient with suspected organophosphate poisoning presents with a low SChE level. However, the confirmatory test, erythrocyte acetylcholinesterase, presents with a normal result. Excluding analytic error, which of the following may explain these conflicting results?
A.) The patient has late-stage hepatic cirrhosis
B.) The patient was exposed to low levels of organophosphates.
C.) The patient has a variant of SChE that displays low activity.
D.) all are true
E.) only A and C are true

Back 62

E.) only cirrhosis and variant are true

Front 63

A patient enters the emergency department in a coma. The physician suspects a drug overdose. Immunoassay screening tests for opiates, barbiturates, benzodiazepines, THC, amphetamines, and PCP were all negative. No ethanol was detected in serum. Can the doctor rule out drug overdose as the cause of this coma with these results?
A.) Yes
B.) No
C.) Maybe

Back 63

B.) No