Poisons and Antidotes Flashcards
Toxin List with Antidotes
- Paraquat
- Organophosphates/Carbamates
- Carbon Monoxide
- Methemoglobinemia Inducers
- Cyanide
- Metals (Iron, Mercury, Lead)
Potential scenarios for poisoning
Therapeutic drug toxicity
Exploratory exposure by young children
Environmental exposure
Occupational exposure
Recreational abuse
Medication error
Prescribing error
Dispensing error
Administration error
Purposeful administration for self-harm/harm another
Toxicity
Toxicity = Inherent capacity of substance to produce injury
Impacted by:
What is the biggest factor affecting toxicity??
DOSE
All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy. PARACELSUS
Therapeutic index . . . what is most worrisome?
Narrow TI
What is the most common route of occupation exposure?
Inhalation
(dermal 2nd)
What is the most common route of exposure in POISONINGS?
Ingestion
Toxicity can be altered by acuity
Example:** Benzene Toxicity**
Acute exposure = CNS depression
Chronic exposure = Leukemia
Mechanisms of antidotes
– Complex with Poison
- NAC/Acetadote/Mucomyst:Acetaminophen
- Crofab:Rattlesnakes,Copperheads
– Biotransformation to Less Toxic Metabolite
• Pyridoxineandthiamine:EthyleneGlycol
• FolicAcid: Methanol
• NAC/Acetadote/Mucomyst:Acetaminophen
– ** Increases Excretion**
• NormalSaline:LithiumToxicity
• UrineAlkalinization:Salicylates
• Hemodialysis
– Block or Compete for Target Receptors
• Fomepizole:EthyleneGlycol/Methanol
– Bypass Effect of Poison
• Octreotide:Sulfonylurea
Initial Treatment Approach for Acute Poisoning
ABCDE
- airway
- breathing
- circulation
- disability
- exposure
Presentations of common toxins
What is bioactivation
mechanism of toxicity, may create a more chemically “active” product
Metabolism
Acetaminophen Metabolism
How Xenobioitics Exert Their Effects
- REceptor-ligand interactions
- Perturbation of membrane function/permeability
- Interference with ATP generation
- Interaction with macromolecules
- Alteration Calcium homesotasis
- Generation of oxygen radicals/oxidative stress
Receptor Ligand Interactions
TCDD >> aromatic hydrocarbon receptor
PCBS >> estrogen receptor
General Types of Reactions w/Macromolecules
Covalent, noncovalent, electron transfer, enzymatic
Hydrogen Abstraction *free radicals often steal hydrogens . . but where it steals it from, then it is a radical *
Oxidative Stress
overproduction of prooxidants
or decrease in antioxidants . . .
Oxidative Stress
Oxidative Stress
can you get reactive oxygen species with normal
p450 reactions?
Yes
(major source = hydroxyl radical)
Lipid Peroxidation
can pull a hydrogen from a fatty acid . . . then the lipid
becomes the radical . . . can become lipid fragments, aldehydes
termination because of antioxidants
*vit E can stop
Antioxidants
Can donate an electron (charitable to radicals)
PARAQUAT
HERBICIDE
Ingestion >> fatal pulmonary fibrosis
MOA: hydroxyl radical >> lipid peroxidation >> cell death
*No antidote = supportive care
Parathione
Metabolized to paraoxon which phosphorylates acetylcholinesterase (inactivates) >> cholinergic crisis SLUDGE!!
– Inhibition of Enzyme Function
Parathione Antidote
- Atropine Sulfate: anti-muscarinic
- Pralidoxime: ACHase activator
Carbon monoxide
Forms carboxyhemoglobin >> Hb(Fe++)CO
*Binds to HGB better than O2!!!
Carbon monoxide
Treat until asymptomatic and_ COHb level <10% _
Oxygen at high partial pressure = displaces CO from Hb
Indications for Hyperbaric Oxygen
– Loss of consciousness, coma, seizure at any time during or after the exposure
– Confusion, cognitive deficits, focal findings, visual symptoms
– MI, dysrhythmias
– Persistent symptoms
**– *Any pregnant patient **
How do you get poisoned with Methemoglobin?
Results from exposure to nitrates, aromatic amines, nitro compounds, antibiotics, local anesthetics
What is Methemaglobin
Hb (Fe++) + NO2 = Hb (Fe+++)
(Methemoglobin) (Dark Blue/Brown)
What is the antidote to methemaglobin?
Methylene blue
Acts as electron donor = reduces Fe+++(ferric) to
**Fe++(ferrous) **
Cyanide
Interference with ATP generation
MOA for cyanide
Binding to, and inhibiting, cytochrome oxidase (binds to Fe+++ in cytochrome a3 = _Blocks aerobic respiration) _
Toxic amounts of cyanide
HCN gas (>50 ppm)
>200 mg cyanide salt = death
Cyanide Antidote
Two step:
– Amyl/Sodium nitrites: Generate Methemoglobin (binds to the iron)
– Hydroxycobalamin: binds CN forming cyanocobalamin
– Sodium Thiosulfate: Forms SCN
What are treatments for metal poisoning?
Chelation
Calcium disodium EDTA: Pb
BAL (dimercaprol): As, Hg, Pb
Dimercaptopropane sulfate (DMPS): As, Hg
Deferoxamine: Fe
Penicillamine: **Cu, Pb, Au, As **
Mercury Toxicities
Mostly inhalation?
– Hg0 and methylmercury HgCl2 are CNS toxicants
– Methylmercury: Low exposure = neurodevelopmental disorders, repro effects
• Minamata disease
– Dimethylmercury: well absorbed topically, lethal (Dr. Karen Wetterhahn), long latent period (~300 days post-exposure)
– Hg0 vapor pulmonary irritant, edema
– Salts corrosive: GI hemorrhage/gastroenteritis and nephrotoxic
MOA of mercury poisoning
Reactivity with sulfhydryl (SH) groups (cysteine) on proteins (inhibition), interacts with selenium
NOTE: the organic ones cross the BBB!
LEAD MOA
Lead interacts with proteins!!
– Reactivity with sulfhydryl (SH), phosphate carboxyl groups on proteins
– Mimics calcium, zinc & iron
CNS effects of lead toxicity
– CNS(many): impaired concentration, headache, encephalopathy, decreased intelligence, altered neurobehavioral development, cognitive decline, stunted growth (children)
Lead antidotes
Antidotes: EDTA, BAL, Succimer (DMSA)
