Final Flashcards
What are the initial non-pharmacologic and pharmacologic priorities when treating a patient with an overdose?
Stabilization:
- ABC management
- Vital signs
- IV access
- Oxygenation
Exposure:
- Medications/illicit substances
- Doses
- Time of ingestion
- Family/EMS report
- Pill count
Assessment:
- Physical exam
- Labs (BMP)
- APAP/salicylate concentrations
- EtOH/toxic alcohol panel
- Decontamination?
- Antidote?
What is the equation to calculate anion gap?
(Na + K) - (Cl + HCO3)
Gap is present if greater than 14
What is the equation to calculate osmolar gap?
Gap = measured - calculated
Calculated = (2 x Na) + (BUN/2.8) + (glu/18) + (EtOH/4.6)
Gap is present if greater than 10
What are the characteristics of these decontamination strategies: activated charcoal, cathartics, gastric lavage, whole bowel irrigation, hemodialysis
activated charcoal - used to prevent absorption.
- Pros: decreases time related problems, absorbs most toxins
- Cons: difficult administration, should not be administered if the airway is unprotected
cathartics - decrease GI transit to help eliminate the substance
- ex. Magnesium citrate, sorbitol
- don’t use commonly, not recommended
gastric lavage -
- use with ingestion of large amounts of substances, if the substance has a high morbidity rate, if activated charcoal doesn’t work, or if they have a jeopardized airway
- Pros: difficult to refuse, comatose patients, use with other agents
- Cons: can cause complications like vomiting aspiration, mechanical injury
- contraindicated in: ingestion of corrosives or hydrocarbons, or depressed gag reflex
whole bowel irrigation: very rare
- use if pt can’t do lavage and if charcoal didn’t work; if they ingested sustained-release products, “body packers/stuffers”, iron, etc.
- continue until the presence of clear rectal effluent
- give through NJ tube due to large volume of PEG needed
hemodialysis:
- use if none of the other methods work or in renal/hepatic failure
- effective for alcohols, lithium, salicylates, and theophylline
What toxicity signs and symptoms are seen in opioid toxicity?
- respiratory depression
- nausea and vomiting
- pinpoint pupils
- drowsiness
- bradycardia
- hypotension
What is the most common agent used for opioid toxicity?
Naloxone - 0.4-2mg IV push, IM, IN
- use lower doses in pts with chronic opioid dependence to avoid withdrawal
- use higher dose in patients with suspected illicit drug use (synthetic opioids)
- consider continuous infusions with longer acting opioids if there’s prolonged signs/symptoms
What is a toxic dose of APAP? What are the high risk and protective conditions for APAP toxicity?
toxic dose: 7.5-15g, can be lower
high risk: malnutrition/chronic illness, concomitant CYP2E1 inducers (isoniazid), chronic alcohol ingestion
protective conditions: acute alcohol ingestion, children
What is the toxic metabolism of APAP?
If the glucuronyl transferase and sulfotransferase pathways of APAP metabolism are saturated, APAP will be metabolized by CYP2E1, which produces NAPQI. NAPQI can be metabolized by GSH transferase to mercapturic acid (not harmful), or go through covalent binding, which results in necrosis.
In 72-96hours, peak AST/ALT levels will be reached, resulting in hepatic encephalopathy, renal failure, and death
What are the main treatment options for APAP toxicity?
NAC: Glutathione analogue that serves as a glutathione surrogate, which can inactivate the toxic APAP metabolite.
- need to obtain APAP concentration at least 4 hours post-ingestion, then look at Rumack-Matthew Nomogram for NAC dosing.
- Most effective when started w/in 8 hours of ingestion
- Preferred to be given IV (3 dose regimen)
Activated charcoal: recommended within the first 4 hours of ingestion
- 1g/kg PO once
- No effect on NAC
What are the toxicity risk factors with salicylate toxicity?
Mixed acid/base disorders: increased anion gap -> metabolic acidosis, early respiratory alkalosis -> hyperventilation
Electrolyte disturbances: hypokalemia, hypo/hypernatremia
Salicylate concentrations:
- 10-15: analgesic properties
- 15-20: anti-inflammatory
- >30: mild toxicity (dizziness)
- > 80: CNS effects
Signs/symptoms: tinntus, vertigo, decreased GI motility, AMS, seizures, lethargy/coma, nausea and vomiting
What is the main salicylate antidote?
Sodium bicarbonate: causes urine alkalinization
- indicated if serum salicylate level is > 30, anion gap metabolic acidosis, or AMS
- 1-2mEq/kg IV push over 1-2 mins
- Monitor serum pH and electrolytes
What are the signs and symptoms of sedative toxicity?
CNS depression, respiratory depression, hypotension, bradycardia
What are our options for sedative toxicity?
Flumazenil: competes with BZDs at the BZD binding site of the GABA complex
- use with caution in pts with seizures, since it can induce seizure activity
- not typically used
What are the toxicity signs and symptoms for TCAs?
AMS, hypotension, tachycardia, prolongs QRS, seizures, anticholinergic symptoms
QRS > 100: increased risk of seizures
QRS > 150: increased risk of cardiac arrhythmias
What is the antidote to TCA toxicity?
Sodium bicarbonate - increases sodium gradient of poisoned sodium channels
- indicated if QRS interval > 100ms, TCA induced arrhythmias or hypotension, or metabolic acidosis
- 1-2 mEq/kg IV push over 1-2 mins
- monitor serum pH
- d/c when QRS interval is < 100ms, resolution of ECG abnormalities, and hemodynamically stable
What are our options for seizure management in TCA toxicity?
- benzodiazepines
- phenobarbital
- maybe phenytoin, fosphenytoin, levetiracetam? these target sodium channels so we don’t know how effective these will be
What are the signs and symptoms of antipsychotic toxicity?
Neuroleptic malignant syndrome (NMS), extrapyramidal symptoms (EPS), hypotension, sedation, tachycardia, QT/QRS prolongation
- toxic doses not well defined
- symptoms usually seen within 1-2 hours of ingestion
- peak symptoms in 4-6 hours
- duration is roughly 12-48 hours
How do we manage the extrapyramidal symptoms of antipsychotic toxicity?
benzotropine 2mg IM
- onset 15-20 mins
- longer 1/2 life
diphenhydramine 1-2mg/kg IV/IM (up to 50mg) over several minutes
- onset 5 mins
- continue with oral therapy for 3-4 days (diphenhydramine 50mg PO TID)
How do we manage neuroleptic malignant syndrome in antipsychotic toxicity?
worried about hyperpyrexia. this occurs 3-9 days after initiating therapy or after adding a second agent.
- haloperidol, depot fluphenazine, or chlorpromazine are the most common offending agents
- death secondary to rhabdomyolysis, renal failure, arrythmias, etc.
- causes higher fever (than serotonin syndrome), lasts > 24 hours, causes diffuse lead pipe rigidity
- Stop the agent
- do rapid external cooling
- benzodiazepines
- dantrolene
- bromocriptine
What are the triad of symptoms for serotonin syndrome? How do we manage serotonin syndrome in antipsychotic toxicity?
- triad of symptoms: AMS, autonomic instability, neuromuscular abnormalities
- development of serotonin syndrome is rapid (within 6 hours)
- lasts <24 hours, lower limbs are more affected than upper limbs
- Stop the agent
- benzodiazepines
- aggressive cooling
- cyproheptadine (periactin): 1st gen histamine receptor blocking agent
What are the signs and symptoms of digoxin toxicity?
Non-cardiac:
- nausea/vomiting
- abdominal pain
- anorexia
- confusion
- vision changes
cardiac:
- bradycardia
- 2nd or 3rd degree heart block
- arrhythmias
- hyperkalemia
How do we manage digoxin toxicity?
- D/C digoxin
- administer activated charcoal if presentation within 2 hours of ingestion
- hemodialysis is not effective
- consider digibind
Digibind (digoxin immune fab): binds free digoxin and tissue bound digoxin released during equilibrium state
- indicated for ventricular arrhythmias, bradycardia, 2nd, or 3rd degree heart block that’s not responsive to atropine
- hyperkalemia (>5.5) with s/sx of toxicity
- serum concentrations > 10-15 drawn at least 6 hours after time of ingestions
- ingestion > 10mg in adults, >4mg in children
- dose by vials based on milligrams of digoxin ingested or serum digoxin concentration
- after administration of digibind, serum digoxin concentrations are useless
What are the signs and symptoms of CCB and BB toxicity?
CCB:
- hyperglycemia
- metabolic acidosis
- pulmonary edema
- ileus (SR)
BB:
- hypoglycemia
- bronchospasms
both:
- hypotension
- bradycardia
- arrhythmias
- cardiogenic shock
- CNS depression
What are the potential antidotes to CCB or BB toxicity?
atropine - blocks parasympathetic activity to increase the heart rate
- use when bradycardia
- not usually effective in CCB and BB overdoses
calcium - enters open voltage sensitive calcium channels to promote calcium release, resulting in myocardial contractility
- more effective in CCB v. BB
- calcium chloride has 2x more elemental calcium vs. gluconate, but extravasation is more likely with chloride form
vasopressors - binds to beta receptors and Gs receptors to stimulate cAMP and calcium release to improve contractility
- may require higher doses to overcome receptor blockade
- if vasodilatory shock -> norepinephrine
- if cardiogenic shock -> epinephrine
glucagon - using as a vasopressor to bypass beta receptor to activate conversion of ATP to cAMP
- may need to pre-medicate with ondansetron and add PRN regimen due to N/V with glucagon
high dose insulin therapy - increases inotropy and intracellular glucose transport
- goal glucose is 100-250mg/dL
- monitor serum electrolytes and improved contractility
lipid emulsion therapy - limits bioavailability of lipophilic medication by creating a “lipid sink”
- give bolus + infusion
- max dose 10mL/kg
What are the phases of iron toxicity?
- 0.5-2hrs post ingestion: non-specific symptoms like GI upset, abdominal pain, hematemesis, hematochezia
- 6-24 hours post ingestion: latent phase resembling recovery
- 2-24hrs post phase 1: shock stage (acidosis, hypotension, hypovolemia, poor cardiac output)
- 48-96 post ingestion: heptatotoxicity
- Days to weeks after ingestions: GI scarring, obstructions, strictures
What is the general management of iron toxicity?
- get serum iron concentration 4 hours post ingestion
- activated charcoal is NOT effective
- KUB scan
- whole bladder irrigation
- consider deferoxamine for chelation
deferoxamine: iron antidote; chelates iron and enhances renal elimination
- indicated in metabolic acidosis or other signs of shock, clinical deterioration despite IV fluid administration, presence of iron tablets on KUB, serum iron concentration > 500mcg/mL
- start at 15mg/kg/hour
How do we interpret anion and osmolar gap results in alcohol toxicity?
anion gap PLUS osmolar gap:
- methanol toxicity
- ethylene glycol toxicity
- alcoholic ketoacidosis
osmolar gap WITHOUT anion gap:
- isopropyl alcohol toxicity
What is the PK/metabolism of ethylene glycol?
- alcohol dehydrogenase in the liver is the first rate-limiting step in the breakdown of ethylene glycol
- t1/2 is 2.5-4.5 hours
What are the phases of ethylene glycol toxicity?
- 30mins-12 hours post ingestion: CNS effects, N/V, inebriation, lethargy/coma (w/in 4-8 hours), seizures
- 12-24hrs post ingestion: metabolic effects, cardiac compromise, anion gap acidosis
- 2-3 days post ingestion: renal effects, acute tubular necrosis w/in 12-48 hours
What is the PK/metabolism of methanol?
- metabolized by alcohol dehydrogenase to formaldehyde, then to formic acid. This reaction is slow, so there is a delay in toxic metabolite formation
- t1/2 is 14-30hrs, peak levels within 20-90 minutes
What are the phases of methanol toxicity?
- headache, dizziness, ataxia, confusion
- during formic acid accumulation: pronounced visual symptoms, anion gap
How do we manage ethylene glycol and methanol toxicity?
non-pharm:
- gastic lavage and aspiration if pt presents in less than 1 hour
- charcoal is NOT effective
- hemodialysis if EG concentration >100mg/dL or methanol concentration > 45 mg/dL, refractory acidosis, renal failure, or symptomatic
pharm:
- ethanol and fomepizole: inhibits alcohol dehydrogenase to limit metabolism of ethylene glycol
- adjunctive therapy to shunt metabolism towards non toxic metabolites: thiamine, pyridoxine, magnesium, folate
- sodium bicarbonate
- correct hypocalcemia and hypoglycemia
What are the side effects of ethanol therapy for alcohol toxicity? What are the upsides to fomepizole?
Ethanol: phlebitis, AMS, hypoglycemia
Fomepizole: No CNS depression, ICU stay not required
What is the PK/metabolism of isopropyl alcohol?
50-80% metabolized by alcohol dehydrogenase to acetone. Acetone is eliminated via kidneys and lungs.
What are the toxic effects of isopropyl alcohol?
- prolonged CNS depression
- nystagmus or miosis
- ketonemia
- hemorrhagic gastritis
- elevated osmolar gap
- increased serum isopropanol concentrations
- bradycardia/hypotension at high concentrations
How do we treat isopropyl alcohol toxicity?
- gastric lavage
- hydration
- correct electrolyte abnormalities
- hemodialysis if lethal doses, coma, or refractory shock
