Antidotes are needed for toxic environmental and industrial exposures. Let's get you familiar with five FDA-antidotes for poisonings -
Antidotes are needed for toxic environmental and industrial exposures. There are several antidotes available for a variety of poisonings. For those interested in emergency medicine and critical care, you should be familiar with these agents (dependent on location). Here are five FDA-approved agents for non-prescribed environmental and industrial poisonings.
#1 - Cyanokit (hydroxycobalamin)
Indication
Treatment of known or suspected cyanide poisoning
Mechanism
Inhibition of nitric oxide synthase
Binds to cyanide by substituting it for the hydroxo-ligand linked to the trivalent cobalt ion, to form cyanocobalamin
Cyanide Poisoning
Exposures from inhalation, ingestion, or dermal exposure to cyanide-containing compounds, including smoke from closed-space fires
Signs and Symptoms of Cyanide Poisoning
Altered mental status | Seizures or coma | Mydriasis | Tachypnea (early) |
Bradypnea (late) | Hypertension (early) | Hypotension (late) | Cardiovascular collapse |
Dosing
5 gm (2.5 gm vial x 2) over 15 minutes
Depending clinical severity and response
May repeat x 1 (max 10 gm) over 15 minutes to 2 hours
ADE (>10%)
Chromaturia (red-colored urine)
Erythema
Rash
Elevated blood pressure
Caution
Hypersensitivity reactions
Interference with clinical laboratory assays
#2 - Antizol (fomepizole)
Indication
Toxic alcohol poisonings
Mechanism
Competitive inhibitor of alcohol dehydrogenase
Toxic Alcohol Poisonings
Ethylene glycol and methanol are metabolized by alcohol dehydrogenase into toxic byproducts
Fomepizole inhibits the metabolism of parent alcohols into toxic metabolites
EG - glycolic and oxalic acid
MET - formic acid
Clinical Presentation of Toxic Alcohol Poisonings
Altered mental status | Seizures or coma | Metabolic acidosis | Blindness (MET) |
Hypocalcemia (EG) | Renal failure (EG) | Cardiotoxic (EG) |
Dosing
FMP 15 mg IV every 12 hours x 4 doses, and then 10 mg IV every 12 hours thereafter
Treat with high clinical suspicion OR serum EG/MET level > 20 mg/dL
Discontinue treatment when asymptomatic with normal pH, and undetectable level or serum level < 20 mg/dL
ADE
Mild side effects reported in package insert; rash
Caution
Renally metabolized (dose adjust in renal impairment and hemodialysis)
Potent CYP2E1 inhibitor
Do not give undiluted - phlebosclerosis
#3 - PROVAYBLUE (methylene Blue)
Indication
Acquired methemeglobinemia
Mechanism
Promotes a non-enyzmatic redox conversion of metHb to hemoglobin.
Metheglobinemia
Dimished oxygen-carrying capacity of hemoglobin secondary to conversion of reduced ferrous (Fe2+) to oxidized ferric (Fe3+)
Clinical Presentation of Metheglobinemia
Cyanosis
Pallor
Metabolic acidosis
AMS
Seizures
Cardiovascular collapse
Dosing
Administer 1 gm/ IV over 5 to 30 minutes.
If methemoglobin remains > 30% or if clinical symptoms persist, may give repeat dose of up to 1 mg/kg one hour after the first dose
Consider alternative treatments after 2 doses
Different off-label dosing regimens have been investigated
ADE (> 10%)
Pain in extremity
Chromaturia
Hyperhidrosis
Dysgeusia
Headache/dizziness
Caution
Serotonin syndrome
Contraindications
Severe hypersensitivity to methylene blue
Glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia
#4 - CroFab [crotalidae polyvalent immune fab (ovine)] and Anavip [crotalidae immune F(ab’)2 (equine)]
Indication
North American crotalid envenomation
Mechanism
Venom-specific antivenom that binds and neutralizes toxins.
Assists with redistribution away from tissues and processed for elimination
Clinical Presentation of Snake Envenomations
Venom burden varies greatly from patient to patient
Administer antivenom with any signs
Local injury
Coagulapathies
System signs of envenomation
Dosing (Product Dependent on Availability/Formulary)
| CroFab | Anavip |
Initial | 4 to 6 vials (max up to 12 has been used) | 10 vials |
Control | 4 to 6 vials PRN q 1 hour | 10 vials PRN q 1 hour |
Maintenace | 2 vials every 6 hours x 3 doses | 4 vials PRN suppression |
CroFab ADE (> 5%)
Urticaria, rash, nausea, pruritus and back pain
Anavip ADE (> 2%)
Pruritus, nausea, rash, arthralgia, peripheral edema, erythema, headache, myalgia, pain in extremity, and vomiting.
Caution
Hypersensitivities, including related-products;
CroFab: papayapapain, chymopapain, papaya extracts, bromelain
Anavip: equine
Delayed serum sickness
Indication
Scorpion sting envenomation
Mechanism
Binds and neutralizes venom toxins
Facilitates redistribution away from target tissues and elimination from the body
Clinical Presentation of Scorpion Envenomation
Autonomic excitation, dysregulation between sympathetic and parasympathetic nervous system
Loss of muscle control, roving or abnormal eye movements, slurred speech, respiratory distress, excessive salivation, frothing at the mouth and vomiting
Dosing
Initiate treatment with Anascorp for patients who develop clinically important signs of scorpion envenomation
Initial: 3 vials over 10 minutes
May repeat 1 vial every 30 to 60 minutes PRN envenomation arrest
Consider alternative treatments after 2 doses
Different off-label dosing regimens have been investigated
ADE (> 2%)
Pyrexia
Rash
Pruritis
Caution
Hypersensitivities, including equine products
Delayed serum sickness
Know What to Give, How to Get
By being familiar with antidotes, you can anticipate procurement and triage inventory issues (vials can go very fast with the snake envenomations). Cyanokit for cyanide toxicity. Fomepizole for toxic alcohols. Methylene blue for methemeglobinemia. CroFab and Snavip for snake envenomations. Anascorp for scorpion stings. Delays in care can potentially be life-threatening; stay on top of communication and stock.
Mark Nguyen, PharmD, BCEMP
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