Toxicology Flashcards
______ -disrupt biologic function and potentially kill an organism.
Poison
_____- 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
Toxin
_____ -toxin that is injected into the victim by some means (e.g., bee sting, snake bite)
Venom
_____ -any harmful substance and is generally
interchangeable with poison
Toxicant
______ -pharmacodynamics (interaction with
molecular targets and mechanisms of effects) as applied to interactions and mechanisms that generate toxic effects
Toxicodynamics
_____ -pharmacokinetics (absorption, distribution, biotransformation, and elimination) as applied to toxic substances
Toxicokinetics
Overdoses & Poisonings cause ___% all hospital admissions and ___% all ICU admissions
1; 10
Majority of overdoses are _______
Pediatric
Ø Usually accidental, peak age 2 years (why?)
Ø Accounts for ~10% pediatric admits
____% of heroin users started with prescription opioids
80
Mechanisms of toxicity
Physical
Chemical
Pharmacologic
Biochemical
“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?
Chemical
“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?
Pharmacologic
“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?
Biochemical
asbestos fibers in the lung are an example of what mechanism of toxicity?
Physical
______ - alters the genetic material of the
cell, resulting in disruption of function
Genomic (genotoxic)
mechanism of toxicity
______ alters DNA structure or function
sufficiently to cause mutations (benzene) or initiate and promote the development of cancers
Mutagenic (carcinogenic)
penicillin-induced hemolytic
anemia is an example of what mechanism of toxicity
Immunologic
phenytoin is associated with development of
cleft lip is an example of what mechanism of toxicity?
Teratogenic
Blood-borne toxicants are also distributed extensively to the _____
Lungs
toxicants that affect the ____ may
influence multiple systems and result in widespread systemic toxicity
Brain
____ receives a large proportion of systemic blood flow
Liver
primary elimination pathway of water soluble metabolites
Kidney
an estimate is essential; dose,
concentration and the amount of toxicant; acute versus chronic
Degree of exposure
T/F dermal exposure is generally associated with reduced rates and extent of absorption compared with oral ingestion or inhalation
T
Time since exposure is helpful in estimating the following
Ø Degree of absorption
Ø Usefulness of blood sampling
Ø Value of management therapies
Serum Overdose Panel
Alcohol, acetaminophen, barbiturate, salicylate,
& tricyclic antidepressants
Types of diagnostic studies in Toxicology management
Serum Overdose Panel
Urine Toxicology Screen
ACTIVATED CHARCOAL for decontamination strategy
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)
GASTRIC LAVAGE decontamination strategy
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)
_____ contains multiple alkaloids (notably
emetine)-causes emesis by direct action on the gastric mucosa & by stimulating the
chemoreceptor trigger zone
Ipecac syrup
Contraindications/considerations to decontamination by emesis
Has not been proven to improve outcomes in overdoses
Most treatments for toxicity are _____
Supportive care
Antidote mechanisms and examples
- 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
Acetominophen overdosing
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)
How does NAC work?
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)
Salicylates
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
emesis not recommended for what type of overdose
Opioid
Oxalate-calcium crystals precipitate in the renal tubules and cause nephrotoxicity for what substances
Ethylene Glycol
Ø toxic metabolites ; high mortality and morbidity if not treated
Ø ethylene glycol converted to glycoxylic acid and then oxalate
_____ is converted to formaldehyde and then formic acid
Methanol
§ causes metabolic acidosis, multi-organ failure and death
§ damage to the retina and optic nerve and blindness
induction of cardiac arrhythmias can occur with what type of overdose
Cardiac Glycosides- digoxin
Organophosphates-characteristics
Ø binds and inhibits acetylcholine esterase- acetylcholine is a key transmitter at muscarinic, nicotinic and CNS synapses
Organophosphates effect on muscarinic and nicotinic receptors
Ø effect on muscarinic receptors- increased salivation and bronchial secretions bronchoconstriction, bradycardia
Ø effect on nicotinic receptors- muscle tremors, weakness and paralysis
Calcium Channel and β-Blockers toxicity is a direct extension of ____
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
