Toxicology General Principles

Question 1

Define Toxicology

Answer 1

The study of poisons

Question 1

Define Posion

Answer 1

any chemical substance which can cause harm

Question 2

Define hazard

Answer 2

likelihood an event will occur based on how the product is packaged, formulated, or its accessibility

Question 3

Define risk

Answer 3

the probability that an event will occur based on patient
vulnerability

Question 4

Define drug Co-ingestant

Answer 4

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

Question 5

Poisoning is the ___ cause of injury deaths and the ___ cause of hospitalizaton

Answer 5

Fourth. fifth

Question 6

The most common cause of poisoning is?

Answer 6

Preascription medicaitons

Question 7

Approximately ___ of people taking acetaminophen in Canada overdose

Answer 7

10 000

Question 8

WIth opioid related poisonings ___ involved opioids that were non-pharmaceutical

Answer 8

88%

Question 9

Toxicology is the study of AE of chemicals on living systems including: (5)

Answer 9

*Mechanisms of action 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 adverse effects of chemicals.

Question 10

What is ED50?

Answer 10

dose at which 50% of population therapeutically responds. (ED50=1 mg/kg)

Question 11

What is the TD50?

Answer 11

dose at which 50% of population experiences toxicity (TD50=10 mg/kg).

Question 12

What is the LD50/

Answer 12

dose at which 50% of population dies (LD50=100 mg/kg).

Question 13

What does ED, TD and LD stand for?

Answer 13

Effective dose, Toxic dose, lethal dose

Question 14

What is the NOAEL score?

Answer 14

Highest dose at which - no observed
adverse effect level

Question 15

What is the LOAEL?

Answer 15

Lowest dose at which - observed adverse
effect level

Question 16

What is the TI?

Answer 16

TI is the ratio of the doses of the
toxic and the desired responses.

Question 17

How is the therapeutic index calculated?

Answer 17

Question 18

TI is used an index of ___ toxicity of two different materials

Answer 18

comparative

Question 19

The larger the ratio of the TI?

Answer 19

the greater the relative safety.

Question 20

Which drug is safeR?

Answer 20

Drug A

Question 21

Example of a poisoning scale

Answer 21

Question 22

Define Mechanistic

Answer 22

cellular, biochemical and molecular
mechanisms by which chemicals cause toxic
responses

Question 23

Define Foresnic

Answer 23

cause of death, legal aspects

Question 24

Define clinical

Answer 24

treatments for poisonings and injuries caused by xenobiotics

Question 25

Can you determine LD50 on human clinical trial?

Answer 25

No, unethical, we are even trying to reduce the usage of mice

Question 26

Define environmental

Answer 26

environmental pollutants, effects on flora and fauna

Question 27

Define Food

Answer 27

Adverse effects of processed or natural food components

Question 28

Define regulatory

Answer 28

assigns risk to substances of commercial importance (toxicology meets regulations/policies).

Question 29

What are the factors affecting toxicity?

Answer 29

Route and site of exposure Duration of exposure Elimination rate and frequency of expsorue

Question 30

What are the major routes and site of exposure?

Answer 30

Major poisons access the body via: * GI (77%) * Lungs * Skin * Parenteral routes - most toxic and rapid response (BYPASS FIRST PASS) * Ocular * GU and other routes

Question 31

Define acute duration of exposure?

Answer 31

Acute: within previous 24 h

Question 32

Define subacute duration of exposure

Answer 32

Subacute: repeated exposure x 14 d

Question 33

Define Subchronic duration of exposure

Answer 33

* Subchronic: repeated exposure x 3 m

Question 34

Define Chronic duration of exposrue

Answer 34

* Chronic: repeated exposure > 6 m

Question 35

Review the next slide with regards to elimination and frequency of exposure

Answer 35

Notice A is eliminated slow, B is = frequency of dose, C= fast elimination

Question 36

Define Absorption

Answer 36

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

Question 37

Describe the Flow of blood from digestive to arterial circulation

Answer 37

1. GI: Cmax is low and Tmax is large 2. IV– Drug does not undergo first pass metabolism. Cmax is larger and Tmax is smaller. Even though the conc of the drug administered is same. 3. Inhalation (Lungs) – Cmax is even large and Tmax is further smaller. E.g. anaesthetics.

Question 38

Different routes of administration may cause different ___ and ___ at the same concentration of the drug

Answer 38

Cmax and Tmax

Question 39

Review the next slide

Answer 39

Question 40

Enterohepatic circulation drgus?

Answer 40

E.G. ANTIBIOTICS, NSAID, WARFARIN, OPIOIDS, DIGOXIN

Question 41

What may be the pharmacological effect of the toxicant itself?

Answer 41

* Gastric hypomotility or delayed gastric emptying from anticholinergic effect * Pathophysiologic consequences: hypotension, hypothermia → hypoperfusion

Question 42

Curve 3 falls faster than curve one because

Answer 42

ate of excretion is proportional to the current conc of the drug as the drug follows first order kinetics.

Question 43

Half-life of the drug is same regardless

Answer 43

of the route of administration. Half-life is drug characteristics and not route based.

Question 44

Where is absorption in oral exposure mostly?

Answer 44

Small intestine

Question 45

Pharmacobezoars

Answer 45

formation of four different extended-release formulations

Question 46

Distribution can be divided into 4 categories

Answer 46

Blood, Extracellular fluid, fat, intracellular fluid

Question 47

Volume of distribution?

Answer 47

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

Question 48

What is the Vd equation

Answer 48

Question 49

What is Kc dependant on?

Answer 49

Permiability of barriers pH of compartments Binding capacity Drug characteristics

Question 50

Equilibrium constant Kc is a number that-

Answer 50

Tells if the balance is in forward or backward direction.

Question 51

What is distribution

Answer 51

Blood flow, Plasma protein binding Vd, transporters, pH of the blood

Question 52

What is the toxic effect compartment?

Answer 52

* May differ from therapeutic effect compartment * Onset of toxicity depends on the rate of distribution to the toxic effect compartment

Question 53

Example of Toxic effect compartment

Answer 53

Lead in liver and stored in bone, Lithium to plasma and brain

Question 54

What does Glucuronosyltransferases lead to

Answer 54

glucuronidation

Question 55

What are some factors affecting metabolism (3 main ones)

Answer 55

Enzyme Saturation Genetic polymorphism Variation

Question 56

What are the variation factors affecting metabolism?

Answer 56

Rate of blood flow, protein binding and the intrinsic ability (organ clearance)

Question 57

What are the elimination mechanisms?

Answer 57

Kidney, liver

Question 58

The renal excretion of drugs is the result of different mechanisms:

Answer 58

glomerular filtration, passive back diffusion, tubular secretion and tubular reabsorption (saturable).

Question 59

Things to consider for renal excretion (3)

Answer 59

* Passive filtration: relies on filtrate pH and blood flow rate * Changes to blood pH: may cause ion trapping * Saturation of active secretion: may lead to accumulation

Question 60

What are the approaches to the poisoned patient?

Answer 60

Question 61

SLIDE RESUSCITATION AND STABILIZAITON