General Principles Of Toxicology

Question 1

What is toxicology?

Answer 1

The study of poisons

Question 2

What is a toxicologist?

Answer 2

One who studies poisons

Question 3

What is a poison?

Answer 3

Any chemical substance that can cause harm

Question 4

Differentiate hazard and risk.

Answer 4

Hazard: likelihood an event will occur based on how the product is packaged, formulated, or its accessibility
Risk: the probability that an event will occur based on patient vulnerability

Question 5

Define drug overdose.

Answer 5

Taking a harmful amount of a drug

Question 6

What is a co-ingestant?

Answer 6

Xenobiotic (foreign substance) in circulation at the time of toxicity

Question 7

Why is toxicology important?

Answer 7

Among Canadians of all ages, poisoning is the 4th leading cause of injury deaths and 5th leading cause of hospitalization
Most common cause of poisoning is Rx medication
10,000 people overdose on acetaminophen annually in Canada
88% of opioid hospitalizations were non-pharmaceutical

Question 8

Provide a more detailed definition of toxicology.

Answer 8

Study of adverse effects of chemicals on living systems, including:
-MOA and exposure to chemicals as a cause of acute and chronic illness
-Understanding physiology and pharmacology by using toxic agents as chemical probes
-Recognition, identification, quantification of hazards from occupational exposure to chemicals
-Discovery of new drugs and pesticides
-Development of standards and regulations to protect humans and the environment from AEs of chemicals

Question 9

Differentiate ED, TD, and LD.

Answer 9

ED: effective dose (therapeutic dose of a drug)
TD: toxic dose (dose at which toxicity occurs)
LD: lethal dose (dose at which death occurs)

Question 10

Differentiate ED50, TD50, and LD50.

Answer 10

ED50: dose at which 50% of the population therapeutically responds
TD50: dose at which 50% of the population experiences toxicity
LD50: dose at which 50% of the population dies

Question 11

What is the TI?

Answer 11

Therapeutic index
-ratio of the doses of the toxic and desired response
-used as an index of comparative toxicity of two different materials
-approximate statement of the relative safety of a drug

Question 12

What does a larger TI signify?

Answer 12

The larger the ratio, the greater the relative safety

Question 13

How do you calculate the TI?

Answer 13

TI = TD50/ED50

Question 14

What are the different branches of toxicology?

Answer 14

Mechanistic: cellular, biochemical, and molecular mechanisms by which chemicals cause toxic response
Forensic: cause of death, legal aspects
Clinical: treatment for poisonings and injuries caused by xenobiotics
Environmental: environmental pollutants, effects on flora and fauna
Food: adverse effects of processed or natural food components
Regulatory: assigns risk to substances of commercial importance

Question 15

What are the factors affecting toxicity?

Answer 15

Route and site of exposure
-GI (77%)
-lungs
-skin
-parenteral routes (most toxic and rapid response due to bypassing 1st pass)
-ocular
-GU and other routes
Duration of exposure
-acute: within previous 24h
-subacute: repeated exposure x 14d
-subchronic: repeated exposure x 3m
-chronic: repeated exposure > 6m
Elimination and frequency of exposure

Question 16

What are some examples of drugs that undergo enterohepatic circulation?

Answer 16

NSAIDs
Antibiotics
Warfarin
Opioids
Digoxin

Question 17

What is toxicokinetics?

Answer 17

PK of toxic substance
-these characteristics may be different with respect to doses within therapeutic doses
-pharmacologic effects of the toxicant itself may affect the TK

Question 18

Why is absorption important in toxicokinetics?

Answer 18

Rate and extent of absorption are important because they determine concentration and ultimately, the likelihood of toxic effect

Question 19

Differentiate Cmax and Tmax for oral, IV, and inhaled routes of admin.

Answer 19

oral: Cmax is low and Tmax is large
IV: Cmax is larger and Tmax is smaller even though conc of drug administered is same (skips 1st pass metabolism)
inhalation: Cmax is even larger and Tmax is further smaller

Question 20

Does AUC differ between routes of administration?

Answer 20

no
different routes may cause different Cmax and Tmax at same conc of drug but AUC is the same

Question 21

Why does the curve of inhaled route of admin fall faster than oral route?

Answer 21

rate of excretion is proportional to the current conc of the drug as the drug follows 1st order kinetics

Question 22

What happens with half-life as route of admin changes?

Answer 22

half-life of the drug is same regardless of the route of admin

Question 23

What are pharmacobezoars?

Answer 23

mass trapped in GI system
-can cause lack of blood flow to colon which may cause secondary adverse effects
-if they are dissolve, they can cause a whole lot of other toxicant effects

Question 24

What are the 4 compartments that drug can distribute into?

Answer 24

fat
blood
extracellular fluid
intracellular fluid

Question 25

What is Kc?

Answer 25

equilibrium constant
-number that tells if the balance is in forward or backward direction

Question 26

What is Kc dependent on?

Answer 26

permeability of barriers
pH of compartments
binding capacity
drug characteristics (such as fat solubility)

Question 27

What is volume of distribution?

Answer 27

how much of the drug needs to be in the body to get a certain conc in the plasma

Question 28

What is the equation for Vd?

Answer 28

amount of drug in the body (mg) / plasma concentration of the drug (mg/L)

Question 29

Differentiate a high and low Vd drug.

Answer 29

a drug with a high Vd has a propensity to leave the plasma and enter the extravascular compartments of the body
-higher dose required to achieve a given plasma concentration
a drug with low Vd likes to remain the plasma
-lower dose of a drug required to achieve a given plasma concentration

Question 30

What are the factors impacting distribution?

Answer 30

blood flow
plasma protein binding
volume of distribution
transporters (genetic polymorphisms)
pH of the blood (affects how the toxicant is moving through the body)

Question 31

What are the three things CYP enzymes can do to a drug?

Answer 31

oxidation
hydroxylation
hydrolysis

Question 32

What is the purpose of phase II metabolism?

Answer 32

adding another group to the drug to make it more soluble for excretion

Question 33

What are the factors affecting metabolism?

Answer 33

saturation
-shifts kinetics from 1st order to zero order
-cofactors/enzymes
genetic polymorphisms
variation - rate of blood flow, protein binding, and the intrinsic ability

Question 34

What are examples of high and low extraction ratio drugs?

Answer 34

low extraction: CBZ, warfarin
high extraction: propranolol

Question 35

What is drug clearance?

Answer 35

volume of plasma cleared of a drug over a specified period of time

Question 36

What are the four mechanisms of renal excretion?

Answer 36

glomerular filtration
passive back diffusion
tubular secretion
tubular reabsorption
reabsorption and secretion are active methods and occur through transporters, prone to polymorphisms

Question 37

Who do you report toxic ingestions to?

Answer 37

PADIS

Question 38

What is the approach to a poisoned patient?

Answer 38

1. resuscitation and stabilization
2. history and physical exam
3. symptomatic & supportive care
4. diagnostic testing
5. decontamination
6. elimination
7. antidote

Question 39

What is involved in resuscitation and stabilization?

Answer 39

ABCs
airways
breathing
circulation (BP and HR)

Question 40

What kind of info should be gathered for a poison patient?

Answer 40

who? (age, sex, weight)
what? (all meds and substances)
when?
where?
why? (intentional or accidental?)

Question 41

Differentiate hyperthermia and fever.

Answer 41

hyperthermia:
-increased heat production or decreased heat loss
-caused by drugs
fever:
-thermal set point in the hypothalamus is increased
-caused by microorganism, drugs, etc

Question 42

Differentiate bradycardia, tachycardia, tachypnea, and bradypnea.

Answer 42

bradycardia: decreased HR
tachycardia: increased HR
bradypnea: decreased RR
tachypnea: increased RR

Question 43

What is the first thing to do when a person is exhibiting an altered mental status or seizures?

Answer 43

check blood glucose

Question 44

What is methemoglobinemia?

Answer 44

hemoglobin can carry oxygen but cant release it
-can be caused by benzocaine, dapsone, nitrites
-consider if cardiac and pulmonary diseases ruled out for cyanosis

Question 45

What is diaphoresis?

Answer 45

excessive sweating
-can be caused by sympathomimetics

Question 46

List different breath odours and their likely cause.

Answer 46

fruity or “nail-polish remover”: acetone
garlic: organophosphates
mothballs: napthalene
wintergreen: methylsalicylate

Question 47

What are the three things that can lead to vomiting/hematemesis?

Answer 47

direct GI mucosal irritation
chemoreceptor trigger zone (CTZ) stimulation
intracranial hemorrhage (pressure)

Question 48

What can lead to diarrhea?

Answer 48

intestinal irritation
increased autonomic bowel activity

Question 49

What are toxidromes?

Answer 49

comprise a constellation of clinical signs and symptoms which, taken together, are likely associated with exposure from certain classes of toxicological agents

Question 50

What are the ways to distinguish if a person is experiencing toxicity due to an anticholinergic or a sympathomimetic?

Answer 50

anticholinergic: dry skin, no bowel sounds, urinary retention
sympathomimetic: wet skin, hyperactive bowel sounds, no retention

Question 51

What is the treatment of metabolic acidosis?

Answer 51

sodium bicarbonate

Question 52

What are the pros and cons of toxicity screens?

Answer 52

pros
-identify most drugs present in overdose patients
cons
-may not add information to whats already gathered
-rarely affect treatment course or how to manage
-misinterpretation of a positive drug of abuse