Toxins and Antidotes (Test 1)

antidotes

therapeutic agents that negate the effects of toxins/poisons

increase

Antidotes __________ therapeutic index. This is because they increase the mean lethal dose of a toxin.

1) prevent toxin absorption

2) bind and neutralize the toxin directly

3) interfere with or inhibit the end-organ effect of the toxin

4) inhibit the conversion to more toxic metabolites

What are the 4 things that antidotes can do?

1) decrease toxin level

2) blocking the site of action for the toxin

3) decreasing toxic metabolites

4) counteracting the effects of the toxin

What are the 4 mechanisms for how antidotes are effective?

-decrease absorption

-bind to the toxin (chelation)

-immunotherapy

-lipid sink

-enhance elimination

What are the mechanisms of action that decrease toxin levels?

decrease absorption MOA

absorbs chemicals within minutes of contact, reduces systemic absorption

activated charcoal

What is the antidote to these?

-ACE inhibitors

-Amphetamines

-some antidepressants

-Aspirin

-Carbamazepine

-Dapsone

-Diuretics

-Quinine

-Phenobarbitone

-Theophylline

-substances with anticholinergic or opioid properties

-Plant toxins (phytotoxins)

Ricin

plant toxin that has an antidote of activated charcoal that decreases absorption to decrease toxin levels

alcohols, inorganic salts (sodium chloride), metals, organic solvents (acetone), acids/bases, cyanide

Activated charcoal works for many toxins but what does it not work on?

bind to the toxin MOA

antidote binds to the toxin to form a stable, nontoxic, soluble compound that can be excreted

Dimercaprol (chelators)

What is the antidote to metals that uses the bind to the toxin mechanism of action?

immunotherapy MOA

antibodies bind to toxin

Digi-Fab

What is the antidote for the toxin Digoxin that uses the immunotherapy MOA?

Anti-venom

What is the antidote for the toxin, Venom? The MOA used is immunotherapy.

systemic effects of rattlesnake venom

vomiting, metallic taste in mouth, shock

severe pain, swelling, obvious fang marks

What will you see with envenomation?

anti-venom IV

antibody fragments bind to venom components in circulation and neutralize the activity of the venom (digestion enzymes won't spread as quickly)

NO

Are incisions and suction, tourniquets, and ice packs effective field remedies for rattlesnake venom?

lipid sink MOA

-sequesters lipid-soluble toxicants from tissues by expanding the lipid compartment within intravascular space

-they are formed when a lipid emulsion enters the blood

Intralipid (lipid emulsion)

What is the antidote for the toxins: Bupivacaine, Propranolol, Verapamil (lipid-soluble drugs)?

use a lipid sink (lipid emulsion) to bind and sequester the toxin

If you have a local anesthetic that has become toxic to the body what should you do?

enhance elimination Hemoperfusion MOA

-blood is passed through a column containing activated charcoal or an anion exchange resin

-protein bound substances bind to the column material and thus removed from circulation

Hemoperfusion

What is the antidote that works by enhance elimination MOA for the toxins: Paraquat, Theophylline, Aluminum, Phenobarbital, Aspirin (protein bound toxins, high lipid solubility, and/or high Vd) ?

Enhance elimination Urinary arlkalinization MOA

increases the ionized form of the toxin- less is reabsorbed

urinary alkalinization

What is the antidote that uses enhance elimination MOA used for the toxins: tricyclic antidepressants, salicylate?

lipid sink, enhance elimination, decrease absorption

Which methods from the decreasing toxin levels mechanism for antidotes are non-specific?

A. Lipid sink

B. Enhance elimination

C. Decrease absorption

D. Immunotherapy

-competitive receptor block

-competitive enzyme block

-reactivation of enzyme activity

What are the MOAs that fall under blocking the site of action for the toxin?

competitive receptor block MOA

competitive antagonist or a receptor

Naloxone

What is the antidote for the toxin known as opioids that works with a MOA of competitive receptor block?

Flumazenil

What is the antidote for the toxin known as Benzodiazepine that works with a MOA called competitive receptor block?

competitive enzyme block MOA

competitive inhibition of enzyme that catalyzes the metabolism of a toxin

Fomepizole

What is the antidote for Methyl alcohol and ethylene glycol that works through the competitive enzyme block MOA?

reactivation of enzyme activity MOA

agent reactivates enzyme that is bound by a toxin

Oximes

What is the antidote for organophosphorus that uses a reactivation of enzyme activity MOA?

agricultural workers

Who is normally diagnosed with organophosphorus toxin?

oximes

reactivates enzyme that is bound by a toxin

hemoperfusion

protein bound structures bind to a column

lipid sink

lipid compartment is expanding and lipid-soluble toxicants are sequestered

anti-venom

antibodies bind to the toxin

decreasing toxic metabolites MOA

-sequestering toxic metabolites

-formation of less toxic metabolites

sequestering toxic metabolites

-supports the elimination of toxic metabolites

-frequently the antidote restores enzymes that are required for the elimination process

acetaminophen

-common OTC poisoning

-narrow therapeutic window

symptoms of acetaminophen poisoning

-initially asymptomatic or mild GI upset

-liver injury (24-36 hr)

-liver failure-> metabolic acidosis -> hypoglycemia -> encephalopathy -> death

4 grams

What is the max dose of acetaminophen that an adult can have daily?

7 grams

What is the toxic dose of acetaminophen?

150-200 mg/kg

What is the toxic dose for a child taking acetaminophen?

narrow therapeutic window

Why is acetaminophen poisoning common?

reactive metabolite (N-Acetyl-p-Benzoquinoneimine)

What causes acetaminophen toxicity?

N-Acetyl-p-Benzoquinoneimine (reactive metabolite of Tylenol)

binds to proteins and causes DNA methylation and cell death which leads to liver and kidney toxicity

N-acetylcysteine

-antidote for acetaminophen toxicity

-acts as a glutathione precursor (glutathione conjugates the toxic metabolite which leads to elimination instead of toxicity)

8-10 hours

When is the acetaminophen antidote, N-acetylcysteine, most affective after injection?

formation of less toxic metabolites MOA

-supports reduction of toxin by forming metabolites that are less toxic than the initial toxin

-conversion process

cyanide

-highly toxic and found in rodenticides (rat poison)

-formally a method of execution, fires of plastics, wool, synthetic materials

-binds to cytochrome oxidase and inhibits oxygen utilization which leads to cellular hypoxia and lactic acidosis

cyanide toxicity

-shortness of breath

-agitation

-seizures, coma, hypotension

NO!

Does activated charcoal work for cyanide poisoning?

Cyanokit and Kit of nitrite and sodium thiosulfate

What are the antidotes for cyanide poisoning?

cyanokit

concentrated form of vit B12 (hydroxocobalamin), forms non-toxic products with cyanide

Kit of nitrite and sodium thiosulfate

-nitrite induce methemoglobinemia and binds cyanide to form less toxic byproduct (cyanomethemoglobin)

-thiosulfate converts cyanide to less toxic byproduct (thiocyanate)

-supportive care

-gut decontamination with activated charcoal to reduce absorption (this alone is NOT affective)

What are treatments options for someone with cyanide poisoning besides the antidotes?

counteracting the effects of the toxin MOAs

-mitigating the effect of the toxin

-direct antagonism of the drug action

mitigating the effect of the toxin MOA

counter and mitigate the effect of the toxin

atropine

What is the antidote that counters and mitigates the effect of the organophosphorus toxin?

organophosphorus toxin

causes overstimulation at cholinergic nerve terminals

direct antagonism drug action MOA

directly antagonize the effect of a drug (or toxin)

vitamin K

What is the antidote that directly antagonizes the effect of Warfarin?

Digoxin

Digi-Fab

Benzodiazepine

Flumazenil

Organophosphorus

Oximes

Acetaminophen

N-acetylcystiene

Nitrite and sodium thiosulfate

Cyanide

Warfarin

Vitamin K

venom

Anti-venom

Cyanide

A 54 year old man presents to the emergency department after being rescued from a house fire. The patient is unresponsive on arrival and intubated for airway protection. On physical examination the patient has partial and full thickness burns notes on 30% of his body that spare the patient's mouth and face. No soot or singed nostril hairs noted on examination. Initial lab work indicates acidosis based on lactate levels (12 mmol/L). What is the most likely cause of his acidosis?

B and C

Which of these antidotes supports the formulation of less toxic metabolites?

A. N-acetycystiene

B. Cyanokit

C. Nitrite and sodium thiosulfate

D. Atropine