Toxicology Flashcards
Acetaminophen Measurement Toxicity - Nomogram
Rumack-Matthew nomogram - determines treatment line
Acetaminophen treatment levels
APAP > Nomogram treatment level
Elevated AST with unknown ingestion time and APAP below treatment line
150 mg/kg ingestion and cannot get APAP level within 8 hours
History of chronic toxicity / repeat supratheraputic and elevated AST or
DO NOT Tx IF:
Ingestion > 4 hours ago and below nomogram threshold
Suspected ingestion > 4 hours ago and undetected APAP and no elevation of AST
GI decontamination strategies
Whole bowel irrigation
Gastric lavage
Activated Charcoal
Gastric lavage indications and contraindications
Ingestion within 1 hour (real life is “reasonable time frame” - also based severity of drugs)
- Usually within first 2-3 hours
Substance not bound by AC and has no antidote
Benefits outweigh risks
Contraindications:
Spontaneous Emesis
altered LOC - intubate first
Hydrocarbons, caustic substances or foreign body
High risk for GI injury (esophageal/gastric sx, GI hemorrhage)
Complications:
Aspiration, perforation, laryngospasm, fluid and electrolytes imbalance, dysrhythmia, hypoxia
Activated charcoal indications / contraindications
General: Used to adsorb ingested agents
- Ratio of 10-1: 10 g charcoal for 1 g substance or 1g/kg
Indications:
- Within 1 hour of ingestion
- Dangerous amount of poison adsorbed by charcoal
- Multiple dose may be appropriate after 2 hours for some agents (carbamazepine)
Contraindications:
- Not adsorbed by charcoal: metals or alcohols
- If vomiting presents greater danger: caustic agent or hydrocarbons
- Diminished LOC / unprotected airway
- If endoscopy required or patient at risk for perf / hemorrhage
Whole bowel irrigation indications / contraindications
General: flushes GI tract to decrease transit time
- PEG given at 1-2 L/hr to total of 10 L
Indications:
- Removal of drug packets
- Large ingestion of sustained release drug
- Ingestion of substance not treated by AC
- Lithium and Iron
Contraindications:
- Altered LOC with unprotected airway reflexes
- Decreased GI motility / obstruction / GI hemorrhage / Emesis
What is enhanced elimination
Attempts to increase clearance of a poison after it has been absorbed,
e.g. alkalinization or urine, MDAC, hemodialysis
MDAC
Q2-4 hour dosing of AC - reduced enterohepatic circulation / gut dialysis
Indications:
- Sustained release
- Bezoars
e.g. carbemazepine, quinine, phenobarb, valproic acid, theophylline, dapsone
Risk of bowel obstruction
Can do 2 dose of SDAC for ASA, Dig, Bupropion - this is NOT MDAC.
Urinary Alkalinzation
Increases renal elimination by ion trapping
- Use bicarb infusion at 1.5 - 2x normal maintenance rate
Indications: Weak acids. ASA, methotrexate, phenobarbitol
Contraindications: Renal insufficiency, CHF
Hemodialysis for toxic ingestions
Indications:
- Low molecular weight
- low plasma protein binding
- poor endogenous clearance
- can treat severe acidosis even if the toxin is not dialyzable.
e.g. Alcohols, ASA, Lithium, metformin
ASA
Toxic alcohols
Theophylline
Phenobarb
Lithium
Massive Acetaminophen
Valproic Acid
SANTA - BETA BLOCKERS
Sotalol, Atenolol, Nadalol, Timolol, Acetenolol
Toxidromes: Anticholinergic
altered LOC
DRY skin
mydriasis
hyperthermia
seizures
tachycardia
urinary retention
Tx: Benzos and physostigmine
Toxidromes: Sympathomimetic
agitation
Diaphoresis
Hallucinations
HTN
Hyperthermia
Mydriasis
Muscular rigidity
Tachycardia
Tx: Benzos
Bicarb for wide complex dysrhythmias
Toxidromes: Cholinergic
Altered LOC
Bradycardia
Bronchorrhea
Bronchospasm
N/V/D
Urination
Seizures
Miosis
Salivation
Tx: Atropine, 2-PAM
Toxidromes: Opioid
Miosis
Bradypnea
Altered LOC
Hypothermia
Tx: Naloxone
ECG Changes in Tox: Bradydysrhythmia
B-Blockers
CCB
Cardiac glycosides
Clonidine
ECG Changes in Tox: Tachydysrhythmia
Sympathomimetics
Stimulants
Anti-cholinerigics
For wide complex - give Bicarb
ECG Changes in Tox: QRS Wide
Na+ channel blockers
Quinidine
Sedating antihistamines
Cocaine
TCA
ECG Changes in Tox: QTc Long
Antipsychotics
SSRI / Antidepressantins
Antidysrhythmics
Hydrofluoric acid
ECG Changes in Tox: Ischemia
Stimulants
Sympathomimetics
ECG Changes in Tox: TCAs
Right axis deviation
Terminal R in aVR
QRS prolongation
ECG Changes in Tox: Digoxin
Downsloping ST depression with a characteristic “reverse tick” or “Salvador Dali sagging” appearance
Flattened, inverted, or biphasic T waves
Shortened QT interval
APAP toxicity mechanism
APAP converted to NAPQI in liver
NAPQI binds to cellular proteins and causes hepatotoxicity.
- Centrolobular or zone III
Decreased glutathione in chronic EtOH use, Tylenol use, malnourishment or those on P450 inducing agents (INH, anticonvulsants)
APAP toxic ingestions
Acute Ingestions:
> 6 yrs: >10 g (150 mg/kg)
< 6 yrs: >200 mg/kg
In repeated dosing:
>10 g /day for 24 hours - staggered dosing
> 6 g / day for 48 hours
Children < 6:
>200 mg/kg/d over 24 hrs
> 150 mg/kg/d over 24-48 hrs
> 100 mg/kg/d over 72 hrs
APAP toxicity treatment
N-Acetyl Cysteine NAC
- effective up to 8-10 hrs post.
- ALWAYS GIVE NAC
Oral:
- 140 mg/kg load and 70 mg/kg Q4H for 72 hours
IV
- 150 mg/kg load over 1 hr, then 50 mg/kg over 4 hours then 100 mg/kg over 16 hours.
- Risk of anaphylactoid reactions
If Repeated Supratheraputic doses:
- NAC x 12 hours with repeat APAP and LFTs near end of treatment.
ONTARIO DOSING DIFFERENT
APAP Toxicity Indications for Liver Transplant
King’s College Criteria
pH < 7.3 after resus
or
INR >6.5, Cr > 3.4 mg/dL and grade 3 or 4 hepatic encephalopathy
Remember #3
Creatinine > 300
Grade 3 or 4 encephalopthy
pH < 7.3
INR 6.6 or greater (3.3. x 2)
Mechanisms of NAC
Glutathione precursor
Direct NAPQI conversion
Sulfonization
Free radial Scavenging
Reduces APAP to NAPQI
