Toxicology & Antidotes

pharmacists should be familiar with the recommendation of…

American Society of Health System Pharmacists (ASHP)

what resources contain toxicology information?

1. Micromedex

2. Lexicomp

what drug is excluded from the C-R packaging requirement?

nitroglycerin SL tabs

what should you do for topical exposure?

remove contaminated clothing and wash skin with soap and water for at least 15 minutes

what should you do for ocular exposure?

remove contact lenses and rinse eyes with a gentle stream of water for at least 15 minutes

what should you do for oral ingestion toxication?

remove any remaining substances from the mouth. if there are symptoms of burning or irritation drink a small amount of water or milk immediately

what product that induces emesis is no longer recommended?

ipecac syrup

what should you do if a patient is unconscious, having difficulty breathing, agitated, or having a seizure?

call 911!!!

what is CAB

circulation, airway, breathing

what is the first step of CAB?

evaluate if a patient has a pulse

what should you do if a patient is pulseless?

immediately start CPR with chest compressions. Give 2 breaths for every 30 chest compressions

can you use activated charcoal at home for oral ingestion?

no, otc active charcoal is not recommended

activated charocal is most effective when used …

within one hour

how does activated charcoal work?

it absorbs the drug which prevents GI absorption and systemic toxicity

what is the dose of activated charcoal?

1 g/kg

what should happen prior to using activated charcoal?

the airway should be protected to prevent aspiration

what compounds can increase the risk of aspiration with activated charcoal?

hydrocarbons (petroleum products including gasoline and paint thinner)

activated charcoal is contraindicated in these situations

when the airway is unprotected:

• unconscious

• cannot hold head up

• cannot clear throat

Acetaminophen should be limited to … to prevent hepatotoxicity

< 4000 mg per day from all sources

What is the metabolism of acetaminophen in regards to hepatotoxicity?

hepatotoxicity is a dose dependent adverse ffect caused by the increased metabolism of acetaminophen by CYP2E1 to NAPQI

what can NAPQI cause?

NAPQI can bind to liver cell proteins and cause liver injury, and ultimately liver failure

what is phase 1 of acetaminophen overdose?

1-24 hours: asymptomatic or N/V

what is phase 2 of acetaminophen overdose?

24-72 hours

What is phase 3 of acetaminophen overdose?

fulminant hepatic failure (jaundice, coagulopathy, renal failure and/or death

What is phase 4 of acetaminophen overdose?

> 96 hours: the patient recovers or receives a liver transplant

what is the antidote for acetaminophen overdose?

NAC: n-acetylcysteine

**must be given quickly (preferably within 8 hours); the acetaminophen level (drawn 4-24 hours after ingestion) is used as the basis for treatment

what formulations is NAC available in?

oral and IV

what is the acetaminophen level plotted on to determine the risk of hepatotoxicity?

Rumack-Matthew nomogram

N-acetylcysteine (NAC) mechanism

free radical scavenger and precursor to glutathione. ultimately increases GSH, which converts NAPQI to non toxic metabolites

Oral NAC dosing schedule

(using injectable or inhalation): high dose given once, then lower dose for 17 doses. repeat the dose if emesis occurs within 1 hour of admin

IV NAC dosing schedule

three infusions over a total of 21 hours

opioid overdose

the effects of opioids can be reversed if the appropriate antidote, naloxone, is administered quickly

overdose: anticholinergics (atropine, diphenhydramine, dimenhydrinate, scopolamine, atropa belladonna, jimson weed

symptoms: flushing, dry skin, mydriasis, blurry vision

Treatment: physostigmine in rare cases

Apixaban antidote

andexanet alfa (Andexxa)

Rivaroxaban antidote

andexanet alfa (Andexxa)

Dabigatran antidote

idarucizumab (Praxbind)

warfarin antidote

Phytonadione (vitamin K) or prothrombin complex concentrate (Kcentra)

Heparin/LMWH antidote

protamine sulfate

drug overdose: antipsychotics

symptoms: seizures

treatment:

• benztropine for dystonia

• BZD for seizures

drug overdose: benzos

treatment: flumazenil; can cause seizures when used in pts taking benzos chronically

drug overdose: BB

treatment: supportive care, glucagon

drug overdose: CCB

treatment: glucagon and IV calcium

drug overdose: cyanide - smoke inhalation, nitroprusside in high doses/long durations/renal impairment

treatment: hydroxocobalamin (Cyanokit)

drug overdose: digoxin

treatment: Digoxin immune Fab (DigiFab)

drug overdose: ethanol

symptom: increased anion gap

treatment: thiamine (vitamin B1) to prevent Wernicke’s encephalopathy

5-fluorouracil and capecitabine antidote

uridine triacetate

drug overdose: hydrocarbons - petroleum products, gasoline, kerosene, mineral oil, paint thinners

treatment: do NOT induce vomiting; keep patient NPO due to aspiration risk

drug overdose: insulin, hypoglycemics

treatment:

• dextrose injection, oral glucose (do not give if pt is unconscious)

• Glucagon

overdose treatment: isoniazid

treatment: IV pyridoxine (Vit b6) and benzo

drug overdose treatment: iron

deferoxamine (desferal) - iron and aluminum

drug overdose treatment: methotrexate

treatment:

• IV sodium bicarbonate

• leucovorin or levoleucovorin

• glucarpidase

methemglobinemia from topical benzocaine (in OraGel or teething products) dapsone, nitrates or sulfonamides

Methylene blue (ProvayBlue) (CI in G6PD deficiency)

drug overdose: neostigmine, pyridostigmine

treatment: Pralidoxime

drug overdose: nicotine

early symptoms: abdominal pain, nausea

treatment: supportive care (atropine and BZD)

drug overdose: organophosphates, including insecticides and nerve gases

symptoms: block AChe, which increases ACh levels and causes cholinergic SLUDD (salivation, lacrimation, urination, diarrhea/defecation)

treatment:

• atropine (blocks Ach)

• Pralidoxime - relieves paralysis by reactivating acetylcholinesterase

drug overdose: salicylates

treatment: sodium bicarbonate; alkalinizes the urine, which DECREASES drug absorption and INCREASES the excretion of salicylates

drug overdose: stimulants - including amphetamines, ADHD, weight loss drugs

treatment: benzos for seizures or agitation

drug overdose: toxic alcohols - ethylene glycol (antifreeze), methanol

can cause an INCREASE anion gap

treatment: fomepizole

drug overdose: TCAs

overdose can quickly cause fatal arrhythmias

Sodium bicarbonate to dec widened QRS complex

drug overdose: valproic acid or topiramate induced hyperammonemia

treatment: levocarnitine

symptomatic treatment of overdose/poisoning

• support ciruclations, airway, and breathing as impairments can be life threatening

  • use fluids and vasopressors for hypotension, atropine for bradycardia and mechanical ventilation for a compromised airway

  • shallow breathing with somnolence and pinpoint pupils could be an opioid overdose. Administer naloxone

• treat seizures, severe agitation and tachycardia with BENZOS

• treat hypoglycemia with oral carbohydrates (if pt alert), IV dextrose, SC glucagon

• if ECG demonstrates QT prolongation or QRS widening, administer sodium bicarbonate

• check APAP level and use Rumack Matthew nomogram to determine if NAC should be given

toxin: mammal bites

antidote: rabies vaccine + human rabies immune globulin

toxin: snake bites (copperhead, cottonmouth and rattlesnakes)

antidote: crotalidate polyvalent immune Fab (CroFab)