Toxicology - Mata

Question 1

What is a toxic response?

Answer 1

• Change from normal state

o Could be on molecular, cellular, organ or organism level

Question 2

What are the 4 types of toxic response?

Answer 2

1. Local vs systemic
2. Reversible vs irreversible
3. Immediate vs delayed
4. Graded (individual) vs quantal (population)

Question 3

Graded (individual) vs quantal (population) response

Answer 3

• Degrees of the same damage vs. all or none
• Quantal dose-response is extremely important in toxicology and used to determine the median toxic (TD) or lethal (LD) dose of a substance

Question 4

Dose Response Curve

Answer 4

Shows therapeutic index or dose at which 50% of people given drug will have a therapeutic effect

Question 5

ED50

Answer 5

Median Effective dose at which 50% of the population responds

Question 6

TD50

Answer 6

Median Toxic dose at which 50% of the population responds

Question 7

LD50

Answer 7

Median Lethal dose at which 50% of the population responds

Question 8

Therapeutic Index

Answer 8

LD50/ED50

Question 9

On Target Adverse Drug Effects - Intended Tissue

Answer 9

• Dose too high

* Chronic activation or inhibition effects

Question 10

On Target Adverse Drug Effects - Unintended Tissue

Answer 10

• Correct receptor, but incorrect tissue
• Dose too high
• Chronic activation of inhibition effects

Question 11

Off Target Adverse Drug Effects

Answer 11

For both intended and unintended tissues

• Incorrect receptor is activated or inhibited

Question 12

Subtoxic damage

Answer 12

In response to moderate or high doses or drug

Question 13

What can you do to intervene?

Answer 13

• Reduce absorption of toxin
• Reduce or increase metabolism
• Increase excretion of toxin
• Neutralize toxic effect

Question 14

GI Decontamination

Answer 14

• Activated charcoal
o Effectively absorbs all drugs or toxic chemicals
• Gastric lavage
o Use after ingestion of:
• Sustained release drugs
• Xenobiotics not absorbed by activated charcoal

Question 15

Reducing formation of toxic metabolites

Answer 15

Administer agent that alters the production of a toxic metabolite

Question 16

Reducing formation of toxic metabolites - Acetaminophen Example

Answer 16

• Metabolized by P450 to a reactive metabolite that induces hepatotoxicity
• Greater risk to chronic alcoholics or patients taking drugs that alter P450
• Mechanism of antidote
o Replenishes glutathione and reacts directly with NAPQI

Question 17

Reducing formation of toxic metabolites - Methanol and ethylene glycol Example

Answer 17

• Metabolized to form highly toxic acids
• Mechanism of antidote
o Fomepizole competitively inhibits alcohol dehydrogenase, an enzyme which catalyzes the metabolism of ethanol, ethylene glycol, and methanol to their toxic metabolites

Question 18

Increase renal elimination

Answer 18

• Works for weak acids by enhancing increasing urinary pH (ion trapping)
• Antidote
o Sodium bicarbonate (IV)
• Produces urine alkalization (alkaline diuresis)

Question 19

Increase GI elimination

Answer 19

• GI excretion can be enhanced by increasing adsorption of toxin into the lumen
• Antidote
o Multiple doses of activated charcoal
• Increases the intestinal diffusion of drug in blood → drug in lumen

Question 20

Neutralizing toxic effects of xenobiotics

Answer 20

• Antidote: Antagonists
o Prevent binding of toxins with its target site
o Prevent binding of endogenous chemical with its target site

Question 21

Treatment of drug or chemical toxicity

Answer 21

• Antidote: Chemical inactivation
o Bind directly to toxin
• Chelation of heavy metals
o Examples: lead, mercury and iron poisoning
• Antidote: Antitoxin (antibodies to venoms)
o Bind directly to toxic protein from bites of poisonous animals