Toxicology

Question 1

______ -disrupt biologic function and potentially kill an organism.

Answer 1

Poison

Question 2

_____- a poison of biologic origin that does not have the ability to replicate. More loose definition such as “environmental toxin” has been used to describe toxic substances of nonbiologic origin

Answer 2

Toxin

Question 3

_____ -toxin that is injected into the victim by some means (e.g., bee sting, snake bite)

Answer 3

Venom

Question 4

_____ -any harmful substance and is generally
interchangeable with poison

Answer 4

Toxicant

Question 5

______ -pharmacodynamics (interaction with
molecular targets and mechanisms of effects) as applied to interactions and mechanisms that generate toxic effects

Answer 5

Toxicodynamics

Question 6

_____ -pharmacokinetics (absorption, distribution, biotransformation, and elimination) as applied to toxic substances

Answer 6

Toxicokinetics

Question 7

Overdoses & Poisonings cause ___% all hospital admissions and ___% all ICU admissions

Answer 7

1; 10

Question 8

Majority of overdoses are _______

Answer 8

Pediatric
Ø Usually accidental, peak age 2 years (why?)
Ø Accounts for ~10% pediatric admits

Question 9

____% of heroin users started with prescription opioids

Answer 9

80

Question 10

Mechanisms of toxicity

Answer 10

Physical
Chemical
Pharmacologic
Biochemical

Question 11

“reacts chemically with the tissues or body
fluids such as blood to produce harmful effects (e.g., strong acids or bases cause burns)” is an example of what mechanism of toxicity?

Answer 11

Chemical

Question 12

“interacts with endogenous
pharmacologic pathways, resulting in inhibition or overstimulation (e.g., botulinum toxin inhibits release of acetylcholine to cause paralysis)” is an example of what mechanism of toxicity?

Answer 12

Pharmacologic

Question 13

“Reacts biochemically with cellular
constituents to produce cellular damage (e.g., venom of many snakes contains phospholipases that destroy cell membranes)” is an example of what type of mechanism of toxicity?

Answer 13

Biochemical

Question 14

asbestos fibers in the lung are an example of what mechanism of toxicity?

Answer 14

Physical

Question 15

______ - alters the genetic material of the
cell, resulting in disruption of function

Answer 15

Genomic (genotoxic)
mechanism of toxicity

Question 16

______ alters DNA structure or function
sufficiently to cause mutations (benzene) or initiate and promote the development of cancers

Answer 16

Mutagenic (carcinogenic)

Question 17

penicillin-induced hemolytic
anemia is an example of what mechanism of toxicity

Answer 17

Immunologic

Question 18

phenytoin is associated with development of
cleft lip is an example of what mechanism of toxicity?

Answer 18

Teratogenic

Question 19

Blood-borne toxicants are also distributed extensively to the _____

Answer 19

Lungs

Question 20

toxicants that affect the ____ may
influence multiple systems and result in widespread systemic toxicity

Answer 20

Brain

Question 21

____ receives a large proportion of systemic blood flow

Answer 21

Liver

Question 22

primary elimination pathway of water soluble metabolites

Answer 22

Kidney

Question 23

an estimate is essential; dose,
concentration and the amount of toxicant; acute versus chronic

Answer 23

Degree of exposure

Question 24

T/F dermal exposure is generally associated with reduced rates and extent of absorption compared with oral ingestion or inhalation

Answer 24

T

Question 25

Time since exposure is helpful in estimating the following

Answer 25

Ø Degree of absorption Ø Usefulness of blood sampling Ø Value of management therapies

Question 26

Serum Overdose Panel

Answer 26

Alcohol, acetaminophen, barbiturate, salicylate, & tricyclic antidepressants

Question 27

Types of diagnostic studies in Toxicology management

Answer 27

Serum Overdose Panel Urine Toxicology Screen

Question 28

ACTIVATED CHARCOAL for decontamination strategy

Answer 28

Ø Adsorbs molecules to particle surface Ø Reduces GI absorption of many toxic agents Ø Enhances total body clearance of some agents Ø given orally or via orogastric tube as a slurry Ø Adults: 50-100gm (1-2g/kg), Children: 10-25g (1- 2g/kg)

Question 29

GASTRIC LAVAGE decontamination strategy

Answer 29

ØUseful < 2hrs after ingestion ØLonger with agents that are strongly Øanticholinergic ØMay be done in an awake or in unconscious patient after intubation ØWarm tap water (~5 min or until clear)

Question 30

_____ contains multiple alkaloids (notably emetine)-causes emesis by direct action on the gastric mucosa & by stimulating the chemoreceptor trigger zone

Answer 30

Ipecac syrup

Question 31

Contraindications/considerations to decontamination by emesis

Answer 31

Has not been proven to improve outcomes in overdoses

Question 32

Most treatments for toxicity are _____

Answer 32

Supportive care

Question 33

Antidote mechanisms and examples

Answer 33

- Receptor competition: naloxone for opiate - Complex formation: dimercaprol /edetate calcium disodium for heavy metal - Metabolic conversion: Fomepazole and ethanol for methanol or ethylene glycol poisoning - Prevention of toxic metabolite formation: N-acetylcysteine for acetaminophen poisoning - By changing the physio-chemical nature of toxicant: sodium thiosulfate for cyanide poisoning - Promotes return to normal function by repairing a defect or enhancing a function that corrects the effects of poison: vitamin K for warfarin overdose

Question 34

Acetominophen overdosing

Answer 34

Ø Overdose leads to toxic metabolic pathway Ø Acute toxic dose: >140mg/kg in pediatric and >6g in adults Ø Chronic toxic dose: >4g/day in adults Ø Hepatic and renal damage Ø Treatment with prevention of absorption = activated charcoal Ø N-acetylcysteine (NAC)

Question 35

How does NAC work?

Answer 35

N-acetylcysteine (NAC). A primary treatment strategy for acetaminophen toxicity is replenishment of cellular glutathione via the administration of NAC, a precursor of glutathione (manipulation of biotransformation)

Question 36

Salicylates

Answer 36

Ø Available in many over the counter preparations Ø Normal daily dose is 40-60mg/kg; toxic dose 150-500mg/kg Ø toxicity manifests as progressive metabolic, neural, cardiovascular, and renal dysfunction Ø Treatment with prevention of absorption = activated charcoal, emesis not recommended

Question 37

emesis not recommended for what type of overdose

Answer 37

Opioid

Question 38

Oxalate-calcium crystals precipitate in the renal tubules and cause nephrotoxicity for what substances

Answer 38

Ethylene Glycol Ø toxic metabolites ; high mortality and morbidity if not treated Ø ethylene glycol converted to glycoxylic acid and then oxalate

Question 39

_____ is converted to formaldehyde and then formic acid

Answer 39

Methanol § causes metabolic acidosis, multi-organ failure and death § damage to the retina and optic nerve and blindness

Question 40

induction of cardiac arrhythmias can occur with what type of overdose

Answer 40

Cardiac Glycosides- digoxin

Question 41

Organophosphates-characteristics

Answer 41

Ø binds and inhibits acetylcholine esterase- acetylcholine is a key transmitter at muscarinic, nicotinic and CNS synapses

Question 42

Organophosphates effect on muscarinic and nicotinic receptors

Answer 42

Ø effect on muscarinic receptors- increased salivation and bronchial secretions bronchoconstriction, bradycardia Ø effect on nicotinic receptors- muscle tremors, weakness and paralysis

Question 43

Calcium Channel and β-Blockers toxicity is a direct extension of ____

Answer 43

Ø Used for hypertension, heart failure, arythmias and headaches Ø Toxicity is a direct extension of the pharmacologic activity of these agents; use in controlling pressure, arrhythmias and heart failure