Basics Of Toxicology Flashcards
What is toxicology?
The science that relates adverse effects of chemicals, including drugs, to biological systems
Acute toxicity arises from what?
A single or multiple exposure to an agent over 1-2 days
Subacute toxicity occurs from what?
Repeated exposures of an agent over a period no longer than 3 months
Chronic toxicity occurs from what?
Repeated exposures over a period greater than 3 months
What is synergism in toxicodynamics?
when 2 drugs with the same effect are used together, and produce a greater response than what would be expected by adding the responses of each drug used alone
How does volume of distribution (Vd) of a toxin affect the ability to purify it through hemodialysis? (toxicokinetics)
The larger the Vd, the harder it is to purify because the toxin is accumulated in the periphery
What happens to the elimination process at very high and toxic concentrations? (toxicokinetics)
Elimination process may become saturated and toxins/ drugs normally eliminated by 1st order kinetics are now eliminated by 0 order kinetics
What are the primary determinants of toxicity?
- hazard vs risk
- dose/ dose rate
- duration of exposure (AUC)
- route of exposure
How do different routes of exposure affect toxicity?
IV > inhalation > IM > SC > oral > topical
What is biomagnification?
The increase in concentration of toxins from small to large sources/ organisms (ex. phytoplankton vs herring gull)
What are the 2 basic mechanisms of oxidative toxicity and cell death?
- compounds bind directly to cellular components and interfere with normal cell function causing oxidative stress (CO, cyanide, lead)
- compounds undergo redox cycling in the presence of oxygen increasing the formation of ROS (paraquat)
What is necrosis and how does lack of a proper immune response contribute to this process?
The acute, traumatic premature death of cells in living tissue caused by external factors
Lack of a proper immune response leads to a buildup of dead tissue and cell debris
What is apoptosis?
A “programmed” mode of cell death (“cell suicide”)
Apoptosis can occur in what 2 fashions?
Naturally (to benefit an organism) or induced by the chronic exposure to certain toxins
What 4 treatments are used for acute poisoning?
- gastric lavage
- activated charcoal (absorbs toxins)
- induced emesis (ipecac syrup)
- increase the rate of excretion
Under what circumstances is gastric lavage not recommended?
After 4 hours or if:
- 30 min have elapsed since ingestion of corrosive material
- hydrocarbon solvents have been ingested
- coma, stupor, delirium, or convulsants are present
How can you increase the rate of excretion as a way to treat acute poisoning?
- osmotic diuretics
- alter urinary pH (bicarbonate, ammonium chloride)
- hemodialysis and hemoperfusion
What is the rule of thumb for dialysis?
Smaller the Vd, more effective the dialysis
What drugs act to reduce absorption or enhance elimination?
- activated charcoal
- ammonium chlorine
- sodium bicarbonate
What drugs act to chelate metals?
- dimercaprol: arsenic
- penicillamine: copper poisoning (Wilson’s disease, resistant rheumatoid arthritis)
- deferoxamin: iron poisoning
- calcium disodium edetate: lead poisoning
What drugs act to inactivate toxins?
Acetylcysteine- acetaminophen poisoning
What is the mechanism of bleach poisoning?
Oxidative stress
What is the treatment for bleach poisoning and what should not be used?
- remove from skin by flooding with water
- milk, melted ice cream, beaten eggs
- antacids
should not use emesis or lavage
What is the mechanism of ethylene glycol?
- converted to oxalic acid by alcohol dehydrogenase
- alters calcium homeostasis
What is the treatment for ethylene glycol poisoning?
- gastric lavage
- give ethanol (IV) as an antidote
- fomepizole
What is the mechanism of botulinus toxin?
Inhibits the release of Ach
What is the treatment for botulinus toxin poisoning? (as a food-borne toxin)
- emesis, lavage, cathartic
- give equine trivalent antitoxin (ABE)
What is the mechanism of organophosphate insecticide/pesticide poisoning, such as parathion and malathion?
Irreversible cholinesterase inhibitors
What is the notable symptom of organophosphate poisoning?
SLUD S- salivation L- lacrimation U- urination D- defecation
What might severe intoxication/chronic exposure to organophosphates contribute to?
Parkinson’s Disease
What is the treatment for organophosphate poisoning?
- atropine
- gastric lavage or emesis
- 2-PAM
What is the mechanism for organochlorine pesticides such as DDT or dieldrin?
Interfere with the inactivation of the sodium channels and enhances neuron excitability causing rapid repetitive firing
What does chronic exposure to organochlorine pesticides increase the risk of?
Testicular cancer, non-Hodgkin’s lymphoma, and Alzheimer’s
What is the mechanism for chlorophenoxy compounds (TCDD)?
Agonist for aryl hydrocarbon (AH) receptor; induces gene expression
What is the mechanism of paraquat?
Oxidative stress- undergoes redox cycling (ROS)
What is the treatment for paraquat poisoning?
- lavage, cathartics, charcoal
- prolonged observation
What is a halogenated hydrocarbon and what is an example of this?
Carbon tetrachloride (CCl4); chloroform- industrial solvent- fire extinguishers; used in dry cleaning
What is the mechanism of carbon tetrachloride (chloroform) posioning?
- metabolized by a CYP450 to free radicals
- free radical-induced lipid per oxidation causes an increase in intracellular Ca2+ leading to apoptotic cell death
What is the treatment for carbon tetrachloride (chloroform) poisoning?
Remove contaminated clothing, treat symptoms
What is the mechanism of corrosives/ mineral acids, (which are strong acids) poisoning?
Oxidative stress
What is the treatment for corrosive/ mineral acid poisoning and what should you not use?
- dilute the acid with water
- analgesics to reduce pain
- a non-specific antidote is milk of magnesia
should not use gastric lavage or emetic compounds
What is the mechanism for arsenic (a heavy metal) posioning? and how is it absorbed?
- binds to SH groups on metabolic enzymes
- increases oxidative stress
- alters gene expression
What is the treatment for arsenic?
lavage or emesis and dimercaprol
What are notable symptoms of lead poisoning?
Neuromuscular effects- “wrist drop” and “ankle drop”
What is the treatment for lead poisoning?
- chelation (edetate calcium disodium)
- forms organic lead which is likely to cross the BBB
- in the case of severe CNS toxicity, chelation must be used
What is the mechanism of iron in the body?
Oxidative injury
What is the treatment for iron poisoning?
-administer deferoxamine orally and parenterally
What is the mechanism of copper in the body?
Redox cycles; increases oxidative stress
What are the notable symptoms for copper poisoning?
Kayser-Fleischer rings- copper deposits in the cornea
Wilson’s disease
What is Wilson’s disease? (copper poisoning)
Genetic disorder in which the body cannot eliminate copper; copper accumulates in tissue
What is the treatment for copper poisoning?
Penicillamine
What is the mechanism for asbestos in the body?
- redox cycles; increase oxidative stress
- chronic inflammatory action (cytokine activation)
- can increase delivery and activation of carcinogenic chemicals
What is the mechanism for carbon monoxide (CO) (an air pollutant) in the body?
- CO has a greater affinity than O2 for hemoglobin
- forms carboxyhemoglobin, impairs ability of oxyhemoglobin to transport O2
- carboxyhemoglobin is cherry red*
What is the treatment for carbon monoxide poisoning?
-administer O2 by best means available
What is the mechanism of cyanide in the body?
- complexes with ferric iron of cytochrome oxidase
- produces cellular anoxia by inhibiting oxygen utilization in the mitochondria
What are the primary treatments used for cyanide poisoning?
- must be rapid
- cyanide antidote
- sodium thiosulfate (IV)
- sodium nitrite
- rhodanese
