Poisons and Antidotes

Question 1

Toxin List with Antidotes

Answer 1

• Paraquat
• Organophosphates/Carbamates
• Carbon Monoxide
• Methemoglobinemia Inducers
• Cyanide
• Metals (Iron, Mercury, Lead)

Question 2

Potential scenarios for poisoning

Answer 2

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

Question 3

Toxicity

Answer 3

Toxicity = Inherent capacity of substance to produce injury

Impacted by:

Question 4

What is the biggest factor affecting toxicity??

Answer 4

DOSE

All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy. PARACELSUS

Question 5

Therapeutic index . . . what is most worrisome?

Answer 5

Narrow TI

Question 6

What is the most common route of occupation exposure?

Answer 6

Inhalation

(dermal 2nd)

Question 7

What is the most common route of exposure in POISONINGS?

Answer 7

Ingestion

Question 8

Toxicity can be altered by acuity

Answer 8

Example:** Benzene Toxicity**

Acute exposure = CNS depression

Chronic exposure = Leukemia

Question 9

Mechanisms of antidotes

Answer 9

– 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

Question 10

Initial Treatment Approach for Acute Poisoning

Answer 10

ABCDE

1. airway
2. breathing
3. circulation
4. disability
5. exposure

Question 11

Presentations of common toxins

Answer 11

Question 12

What is bioactivation

Answer 12

mechanism of toxicity, may create a more chemically “active” product

Question 13

Metabolism

Answer 13

Question 14

Acetaminophen Metabolism

Answer 14

Question 15

How Xenobioitics Exert Their Effects

Answer 15

1. REceptor-ligand interactions
2. Perturbation of membrane function/permeability
3. Interference with ATP generation
4. Interaction with macromolecules
5. Alteration Calcium homesotasis
6. Generation of oxygen radicals/oxidative stress

Question 16

Receptor Ligand Interactions

Answer 16

TCDD >> aromatic hydrocarbon receptor

PCBS >> estrogen receptor

Question 17

General Types of Reactions w/Macromolecules

Answer 17

Covalent, noncovalent, electron transfer, enzymatic

Hydrogen Abstraction *free radicals often steal hydrogens . . but where it steals it from, then it is a radical *

Question 18

Oxidative Stress

Answer 18

overproduction of prooxidants
or decrease in antioxidants . . .

Question 19

Oxidative Stress

Answer 19

Question 20

Oxidative Stress

Answer 20

Question 21

can you get reactive oxygen species with normal
p450 reactions?

Answer 21

Yes

(major source = hydroxyl radical)

Question 22

Lipid Peroxidation

Answer 22

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

Question 23

Antioxidants

Answer 23

Can donate an electron (charitable to radicals)

Question 24

PARAQUAT

Answer 24

HERBICIDE
Ingestion >> fatal pulmonary fibrosis

MOA: hydroxyl radical >> lipid peroxidation >> cell death

*No antidote = supportive care

Question 25

Parathione

Answer 25

Metabolized to **_paraoxon_** which phosphorylates acetylcholinesterase (inactivates) \>\> cholinergic crisis SLUDGE!! – Inhibition of Enzyme Function

Question 26

Parathione Antidote

Answer 26

* Atropine Sulfate: anti-muscarinic * Pralidoxime: ACHase activator

Question 27

Carbon monoxide

Answer 27

Forms carboxyhemoglobin \>\> Hb(Fe++)CO \*Binds to HGB better than O2!!!

Question 28

Carbon monoxide

Answer 28

Treat until asymptomatic and**_ COHb level \<10% _** Oxygen at high partial pressure = displaces CO from Hb

Question 29

Indications for Hyperbaric Oxygen

Answer 29

– 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 **_

Question 30

How do you get poisoned with Methemoglobin?

Answer 30

Results from exposure to **_nitrates_**, aromatic amines, nitro compounds, antibiotics, local anesthetics

Question 31

What is Methemaglobin

Answer 31

Hb (Fe++) + NO2 = Hb (Fe+++) (Methemoglobin) (Dark Blue/Brown)

Question 32

What is the antidote to methemaglobin?

Answer 32

**_Methylene blue_** Acts as electron donor = reduces Fe+++(ferric) to ## Footnote **Fe++(ferrous) **

Question 33

Cyanide

Answer 33

Interference with ATP generation

Question 34

MOA for cyanide

Answer 34

Binding to, and inhibiting, cytochrome oxidase (binds to Fe+++ in cytochrome a3 = **_Blocks aerobic respiration) _**

Question 35

Toxic amounts of cyanide

Answer 35

HCN gas (\>50 ppm) \>200 mg cyanide salt = death

Question 36

Cyanide Antidote

Answer 36

Two step: – Amyl/Sodium nitrites: Generate Methemoglobin (binds to the iron) – Hydroxycobalamin: binds CN forming cyanocobalamin – Sodium Thiosulfate: Forms SCN

Question 37

What are treatments for metal poisoning?

Answer 37

**_Chelation_** Calcium disodium EDTA: **Pb** BAL (dimercaprol): **As, Hg, Pb** Dimercaptopropane sulfate (DMPS): **As, Hg** Deferoxamine: **Fe** Penicillamine: **Cu, Pb, Au, As **

Question 38

Mercury Toxicities

Answer 38

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

Question 39

MOA of mercury poisoning

Answer 39

Reactivity with sulfhydryl (SH) groups (cysteine) on proteins (inhibition), interacts with selenium NOTE: the organic ones cross the BBB!

Question 40

LEAD MOA

Answer 40

Lead interacts with proteins!! ## Footnote – Reactivity with sulfhydryl (SH), phosphate carboxyl groups on proteins – Mimics calcium, zinc & iron

Question 41

CNS effects of lead toxicity

Answer 41

– CNS(many): impaired concentration, headache, encephalopathy, decreased intelligence, altered neurobehavioral development, cognitive decline, stunted growth (children)

Question 42

Lead antidotes

Answer 42

Antidotes: EDTA, BAL, Succimer (DMSA)