toxicology Flashcards
top medication overdoses
adults - analgesics, sedatives/hypnotics/anti-psychotics, antidepressants, CV drugs, cleaning substances, alcohol
pediatric - cosmetics, cleaning substances, analgesics, foreign bodies, topicals, vitamins
first things first
Stabilization: ABC management***, Vital signs, IV access, Oxygenation
Exposure history: Medications/substances, Dose(s), Time of ingestion, Family/EMS report, Pill count
Assessment: Physical exam, Labs, APAP/ASA concentrations, EtOH/toxic alcohol panel
Decontamination: Activated charcoal, Cathartics, Gastric lavage, Whole bowel irrigation
anticholinergic toxidromes
blind as a bat hotter than hell red as a beet dry as a desert mad as a hatter
urine drug screens detect…
Amphetamines, Barbiturates, Benzodiazepines, Cannabinoids, Cocaine, Opioids, Phencyclidine
anion gap
Difference between primary measured cations and primary measured anions
(Na+ + K+) – (Cl- + HCO3-) *
Gap is present if greater than 14
MULEPAK (methanol, uremia, lactic acidosis, ethanol, paraldehyde, aspirin, ketoacidosis)
osmolar gap
Presence of additional unmeasured low molecular weight molecules that are osmotically active (reference range: 285-300 mOSm/kg)
Gap = Measured - Calculated
Calculated = (2 x Na+) + (BUN/2.8) + (Glu/18) + (EtOH/4.6) ***
Gap is present if greater than 10
activated charcol
44-95% prevention of absorption
Pros: Decreases time related problems, Absorbs most toxins
Cons: Difficult administration, must be given within 4 hours
1-2 gm/kg ABW or 50-100 gm in adults
cathartics
Decreases GI transit
-Magnesium citrate 2-4 mL/kg/dose (up to 300 mL)
-Sorbitol 70% solution 1-2 mL/kg (up to 1 gm/kg)
rarely used due to OTC abuse - weight loss
gastric lavage
“stomach pump”
Efficacy: 8-59%
Complications: Vomiting, Aspiration, Mechanical injury
Advantages: Difficult to refuse, Comatose patients, Use with other agents
Disadvantages: Proper technique, Delay in implementation, Tablet size
whole bowel irrigation
Polyethylene glycol
Sustained-release products, “body packers/stuffers”, iron, lithium
Dosing: 500 mL/hr in children 9 months to 6 years; 1,000 mL/hr in children 6 years to 12 years; 1,000-2,000 mL/hr in adolescents and adults
Patient should remain seated on a bedside toilet
Continue until presence of clear rectal effluent
hemodialysis
Effective for the following medications: Alcohols, Lithium, Salicylates, Theophylline
must have low molecular weight and small V(d)
s/sxs of opioid toxicity
Nausea/vomiting, Drowsiness, Constipation, Pinpoint pupils, Hypotension, Bradycardia, Respiratory depression, Seizure activity
general management of opioid toxicity
ABC management
Monitor vital signs, pulse oximetry, and ECG changes
Monitor signs/symptoms of CNS and respiratory depression
Oxygen supplementation (if needed)
UDS and acetaminophen (APAP)/salicylate concentrations
Administer activated charcoal (if presentation within two hours of ingestion)
Administer naloxone (Narcan®)
opioid antidote
naloxone
Mechanism of action - Antagonizes opioid effects by binding to same receptor sites
Dosing - 0.4 to 2 mg IV push, IM, SQ, ET, or intranasally
-Utilize lower doses initially in patients with chronic opioid dependence due to withdrawal symptoms - GI upset, restlessness, piloerection, hypertension, tachycardia
-May consider continuous infusion with longer acting opioids - Prolonged signs/symptoms; RR under 8 breaths/min to prevent intubation
opioid toxicology tidbits
Severity dependent on medication, dose, duration of action, and patient
Comprises both prescription and illicit drug use - Methadone, Heroin
Aaron’s Law
risk for APAP OD
Induced p450s (CYP2E1 mainly): Isoniazid, Acetone, Chronic EtOH Patients with depleted glutathione: Malnourished, Anorexic, Alcoholics
protected for APAP OD
Children - Increased sulfation pathway, Large liver-to-body ratio
Acute EtOH
Cimetidine and disulfiram - Inhibit CYP2E1
APAP phases of tocivity
1) 0.5 to 24 hours post ingestion - Nausea, vomiting, diaphoresis, malaise, pallor
2) 24-72 hours post ingestion - Hepatic injury (abdominal pain/tenderness, oliguria)
3) 72-96 hours post ingestion - Hepatic failure (jaundice, coagulopathy, encephalopathy, coma)
4) Greater than 96 hours post ingestion - Full recovery or death
APAP tox general management
ABC management
Acetaminophen (APAP) concentration at least 4 hours post ingestion
Toxic doses in acute ingestions
-Adults: 150 mg/kg or 7.5-10 gm (OR 4 grams)
-Children: 200 mg/kg
Administer activated charcoal (if presentation within two to four hours of ingestion)
Evaluate for potential N-acetylcysteine (NAC) therapy using Rumack-Matthew nomogram (can only be used after 4+ hours of ingestion - plots time v conc - 2 lines to represent if tox is unlikely or if probable hepatic tox)
APAP antidote
N-acetylcysteine (Acetadote®)
Glutathione precursor
Mechanism of action: Increases glutathione stores, Acts as a glutathione substitute, Enhances sulfate conjugation
May also have anti-inflammatory, anti-oxidant, inotropic, and vasodilating effects
acetylcystine dosing
IV:
-LD: 150 mg/kg IV over 1 hour
-Second infusion: 50 mg/kg IV over 4 hours
-Third infusion: 100 mg/kg IV over 16 hours
PO:
-LD: 140 mg/kg
-Scheduled regimen: 70 mg/kg PO every 4 hours x 17 doses
capped at 100 kg
salicylate toxicity
Mixed acid base disorders: ↑ anion gap - metabolic acidosis; Respiratory alkalosis (early) - hyperventilation
Electrolyte disturbances: Hypokalemia, Hypo/hypernatremia
Salicylate concentrations:
-Analgesic properties: 10-15 mg/dl
-Anti-inflammatory properties: 15-20 mg/dl
-Mild toxicity: > 30 mg/dL (tinnitus, dizziness)
-Severe toxicity: > 80 mg/dL (CNS effects)
salicylate toxicity s/sxs
CNS: tinnitus, vertigo, delirium, hallucinations, agitation, hyperactivity, seizures, stupor, lethargy
GI: NV
salicylate toxicity general management
ABC management Monitor vital signs and pulse oximetry Salicylate (ASA) concentration Ventilation, ABG BMP to measure anion gap Administer activated charcoal (if presentation within two hours of ingestion) Fluid/electrolyte management Hemodialysis Urine alkalization - Sodium bicarbonate: 1 to 2 mEq/kg (50 to 100 mEq) IV push over 1 to 2 minutes; Continuous infusion may be initiated afterwards and titrated to effect
sedative/hypnotics toxicity s/sxs
CNS depression Respiratory depression Hypotension Bradycardia Hypothermia Rhabdomyolysis
sedative/hypnotics toxicity antidote
Flumazenil (Romazicon®)
Mechanism of action - Competes with BZDs at BZD binding site of GABA complex
Dosing: 0.2 mg IV push
-Use with caution in patients
with seizures - Can induce seizure activity** even in seizure naive patients
-Can induce withdrawal
symptoms - Nausea/vomiting, agitation
TCAs toxicology tidbits
Linked to more drug related deaths than any other prescription medication
-Starting to see less in clinical practice due to new antidepressant medications (e.g., SSRIs)
TCAs in clinical practice
Indications: depression, neuropathy, insomnia, migraines, bed wetting
examples: amitriptyline, doxepin, nortriptyline
TCA PKs
Initially, rapidly absorbed from the GI tract - Anticholinergic effects may slow GI motility, Decrease rate of absorption
Large Vd (10-50 L/kg)
Acidemia increases the percentage of unbound TCA
Highly lipophilic
t1/2 = 4-93 hours
TCA pharmacology
Anticholinergic activity Alpha receptor blockade Serotonin, norepinephrine, and dopamine reuptake inhibition Sodium and potassium channel blockade CNS and respiratory depression
TCA toxicity s/sxs
Altered mental status, Hypotension, Tachycardia, ECG changes (QRS prolongation), Seizure activity, CNS depression, Anticholinergic
symptoms, Drowsiness, Respiratory depression, Decreased GI motility, Metabolic acidosis, Rhabdomyolysis
TCA toxicity effects of QRS prolongation
QRS interval > 100 msec - Increased risk of seizure activity
QRS interval > 150 msec - Increased risk of cardiac arrhythmias
May also result in metabolic acidosis - Promotes unbinding of drug from proteins
TCAs toxicity general management
ABC management
Monitor vital signs and ECG changes
UDS, urinalysis, serum electrolytes, and ABG/VBGs
Serum TCA concentrations?
Fluid hydration +/- vasopressors for hypotension
Seizure activity management (if applicable)
Consider activated charcoal (if presentation within two hours of ingestion and no signs/symptoms of ileus)
Consider sodium bicarbonate based on ECG results (QRS prolongation)
TCA tox antidote
Sodium bicarbonate
Mechanism of action: Increases sodium gradient of poisoned sodium channels
Indications: QRS interval > 100 msec, TCA induced arrhythmias or hypotension, Metabolic acidosis
Dosing: 1 to 2 mEq/kg (50 to 100 mEq) IV push over 1 to 2 minutes
-Continuous infusion may be
initiated afterwards and titrated
to effect
Monitoring
-Serum pH 7.45-7.55
-D/C when: QRS interval under 100 msec, Resolution of ECG abnormalities, Hemodyamically stable
Seizure management of TCA toxicity
**Benzodiazepines - Lorazepam (Ativan®), diazepam (Valium®), midazolam (Versed®) Phenobarbital (Luminal®) Phenytoin (Dilantin®)? Fosphenytoin (Cerebyx®)? Levetiracetam (Keppra®)?
antipsychotics: pharmacology
First Generation - D2 antagonism
Second Generation - 5HT2A/D2 antagonism
antipsychotic examples
typical: haloperidol, fluphenazine, chlorpromazine, thioridazine, perphanazine, trifluoperazine, pimozide
atypical: aripiprazole, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, paliperidone
antipsychotic toxicity S/sxs
CV: Hypotension, Tachycardia, QT and QRS prolongation
neuro: Extrapyramidal symptoms (EPS), Neuroleptic malignant syndrome (NMS), Sedation, Seizure activity
atypical antipsychotics toxicity
Toxic doses are not well defined Often co-ingested with other agents Symptoms are typically seen within 1- 2 hours of ingestion Peak symptoms in 4 - 6 hours Duration is roughly 12 - 48 hours
extrapyramidal sxs
Benztropine 2 mg IM
-Onset ~ 15 - 20 minutes
-Longer half life
Diphenhydramine 1- 2 mg/kg IV/IM (up to 50 mg) over several minutes
-Onset ~ 5 minutes
-Continue with oral therapy for 3 - 4 days - Diphenhydramine 50 mg PO TID
neuroleptic malignant syndrome
Hyperpyrexia up to 42.2C (108F) with altered mental status (delirium or coma) and “lead pipe” muscular rigidity
Occurs 3-9 days after initiating therapy or after adding a second agent
Often these patients are under 40 years of age and more often males
NMS complications
Continues for 5-10 days
84% of cases - Haloperidol, depot fluphenazine, or chlorpromazine use
Death is secondary to rhabdomyolysis, renal failure, cardiovascular collapse, respiratory failure, arrhythmias, or thromboembolism
NMS treatment
D/C offending agent
Rapid external cooling
Benzodiazepines
Dantrolene - Initial dose of 2.5 mg/kg to a maximum of 10 mg/kg IVP; Maintenance dose is 2.5 mg/kg Q6H until resolved
Bromocriptine has also been utilized - 2.5 mg BID initially, increasing to 5 mg TID; Doses as high as 60 mg/day have been used
serotonin syndrome
Toxic hyperserotonergic state - Excessive stimulation of the post-synaptic receptors in the CNS
Triad of symptoms: Altered mental status, Autonomic instability, Neuromuscular abnormalities
Development of serotonin syndrome is rapid - Within six hours of an increase in the precipitating medication
serotonin syndrome: pharmacology
Direct agonists: Buspirone, Lithium, Lysergic acid diethylamide (LSD), Sumatriptan
Increased release of serotonin: Amphetamines, Cocaine, Mirtazapine, MDMA (“ecstasy”)
Inhibitors of serotonin metabolism: Monoamine oxidase inhibitors, Linezolid
Reduced uptake of serotonin:
-Selective serotonin reuptake inhibitors (SSRIs) - Citalopram, fluoxetine, sertraline,
paroxetine
-Tricyclic antidepressants (TCAs) - Amitriptyline, imipramine, nortriptyline
-Serotonin norepinephrine reuptake inhibitors (SNRIs) - Duloxetine, Venlafaxine
-Trazodone
-Dextromethorphan
treating serotonin syndrome
D/C offending agent
Benzodiazepines
Aggressive cooling
Cyproheptadine (Periactin®)
-1st generation histamine receptor blocking agent
-Non-specific 5-HT1A and 5-HT2A receptor blocking effects - 4 mg PO Q1H; Maximum dose: 16 mg
serotonin syndrome vs NMS
SS: lasts under 24 hours, lower limbs more affected
NMS: higher fever, lasts over 24 hours, diffuse lead pipe rigidity
digoxin in clinical practice
Indicated for the treatment of atrial fibrillation (AF) and heart failure (HF)
Monitored with serum concentrations due to narrow therapeutic index
-Goal range usually 0.8 to 2 ng/mL - May be 0.5 to 1 ng/mL in HF
-Must be drawn at least 6 hours after previous dose
digoxin tox s/sxs
Non Cardiac: Nausea/vomiting, Abdominal pain, Anorexia, Confusion, Vision changes
Cardiac: Bradycardia, 2nd or 3rd degree heart block, Arrhythmias, Hyperkalemia( 5 to 6.4 mEq/L ~ 35% mortality, > 6.4 mEq/L ~ 90% mortality)
digoxin toxicity general management
Discontinue digoxin
ABC management
Obtain serum digoxin concentration, BMP
Monitor vital signs and ECG changes (arrhythmias, bradycardia)
Administer activated charcoal (if presentation within two hours of ingestion)
Consider administration of Digibind®
Hemodialysis is not* effective
digoxin antidote
Mechanism of action: Binds free digoxin and tissue bound digoxin released during equilibrium state
Indications: Ventricular arrhythmias, bradycardia/2nd or 3rd degree heart block not responsive to atropine, Hyperkalemia (K > 5.5 mEq/L) with signs/symptoms of toxicity, Serum digoxin concentrations > 10-15 ng/mL drawn at least 6 hours after time of ingestion, Ingestion > 10 mg in adults, > 4 mg in children
dosing: Each vial binds approximately 0.5 mg* of digoxin
-Based on acute ingestion of known amount - Total body load (TBL) = mg digoxin ingested x 0.8; TBL/0.5 mg = # Digibind ® vials to administer
-Based on serum digoxin concentrations in adults
— # Digibind ® vials = digoxin concentration (ng/mL) x patient’s weight (kg) / 100
digoxin toxicology tidbits
Toxicity can occur with acute ingestion and chronic therapy
Must correlate signs/symptoms with serum concentration - Time of ingestion? Time of concentration?
Serum digoxin concentrations are clinically useless after Digibind® administration
CCBs and BBs in clinical practice
CCBs: Angina, Hypertension, Arrhythmias (e.g., AF), HF
BBs: Angina, Hypertension, Arrhythmias, HF, Myocardial infarction, Migraine headaches, Tremor, Portal hypertension
CCB and BB toxicity s/sxs
CCBs: Hyperglycemia, Metabolic acidosis, Pulmonary edema, Ileus (SR)
BBs: Hypoglycemia, Bronchospasm
both: Hypotension, Bradycardia, Arrhythmias, Cardiogenic shock, CNS depression
CCB and BB general management
ABC management
Monitor vital signs and ECG changes (arrhythmias, bradycardia)
Administer activated charcoal (if presentation within two hours of ingestion)
Potential antidotes: Atropine, Calcium, Vasopressor therapy, Glucagon, High dose insulin therapy
CCBs and BBs : atropine
Mechanism of action: Blocks parasympathetic activity to increase heart rate
Dosing: 0.5 to 1 mg IV push - Maximum dose: 3 mg
CCBs and BBs : calcium
Mechanism of action: Enters open voltage sensitive calcium channels to promote calcium release from sarcoplasmic reticulum resulting in myocardial contractility, More effective in CCB overdoses vs BB overdoses
Dosing: Calcium chloride: 5 to 10 mL of 10% solution; Calcium gluconate: 10 to 20 mL of 10% solution
-Note: Calcium chloride has three times more elemental calcium than calcium gluconate
CCBs and BBs : vasopressor therapy
May require higher doses to overcome receptor blockade
Medication selection depends on clinical presentation
-α stimulates effects on blood pressure
-β stimulates effects on heart rate
Review patient’s ingestion history and monitor vital signs to select appropriate agent
CCBs and BBs : glucagon
Mechanism of action: Bypasses beta receptors and acts directly on Gs to stimulate conversion of ATP to cAMP
Dosing: 3 to 10 mg IV bolus (adults); 50 to 150 mcg/kg IV bolus (children)
-Initiate infusion at same dose as effective bolus dose (in mg/hr) - Patient responds to 5 mg IV bolus, start infusion at 5 mg/hr
CCBs and BBs : high dose insulin therapy
Mechanism of action: Facilitates myocardial utilization of carbohydrates
Dosing: Insulin drip at 0.5 to 1 unit/kg/hr IV; Dextrose at 0.5 gm/kg/hr IV
-Titrate to systolic blood pressure > 90 to 100 mm Hg or effect every 30 to 60 minutes (improved contractility, decreased symptoms)
Monitoring: Improved contractility within 15 to 60 minutes; Goal glucose: 100 to 250 mg/dL; Serum electrolytes every 1 to 2 hours (glucose, potassium)
CCBs and BBS: toxicology tidbits
Atropine - Not likely to be effective in either CCB or BB overdoses
Calcium - More likely to be effective with CCB overdoses vs BB overdoses; Chloride has three times more elemental calcium vs. gluconate, but extravasation more likely with chloride formulation
Vasopressor therapy - Should utilize higher doses to overcome beta receptor blockade
Glucagon - May need to pre-medicate with ondansetron (Zofran®) and add PRN regimen due to nausea/vomiting with glucagon
High dose insulin therapy - Communicate with health care providers to address patient safety
Iron toxicology tidbits
Toxicity can occur at 10 to 60 mg/kg of elemental iron
Prenatal vitamins contain approximately 65 mg of elemental iron
Children’s vitamins contain approximately 10 to 18 mg of elemental iron
Concern is absorption of iron into tissue - Can still experience toxicity with normal serum iron concentrations
Human body has no natural mechanism to handle iron overload
-Excretion: Male = 1 mg daily; Female = 2 mg daily
Iron phases of toxicity
1) 0.5 to 2 hours post ingestion - GI upset, abdominal pain, hematemesis, hematochezia
2) 6 to 24 hours post ingestion - Latent phase resembling recovery; continue to monitor
3) 2 to 24 hours post phase 1 - Shock stage (acidosis, hypotension, hypovolemia, poor cardiac output)
4) 48 to 96 hours post ingestion - Hepatoxicity
5) Days to weeks post ingestion - GI scarring, obstructions, strictures
iron tox - general management
ABC management Monitor vital signs Fluid hydration Serum iron concentration 4 hours post ingestion Activated charcoal is not effective KUB (kidneys, ureter, and bladder) scan Whole bowel irrigation Consider administration of deferoxamine for chelation
iron antidote
Deferoxamine (Desferal®)
Mechanism of action: Chelates iron and enhances renal elimination
Indications: Metabolic acidosis or other signs of shock, Clinical deterioration despite IV fluid administration, Presence of iron tablets on KUB Serum iron concentration > 500 mcg/mL
dosing: Start at 15 mg/kg/hour - May increase to 45 mg/kg/hour for patients with severe poisoning; Decrease rate if patient experiences hypotension - Usually continued for 12 to 24 hours; May titrate down based on resolution of symptoms and/or absence of vin rose urine
toxic alcohol examples
Ethylene glycol - Antifreeze, brake fluid, and industry solvents
Methanol - Windshield washer fluid, paint remover, copier fluid, some antifreeze, and some engine fuels
Isopropyl alcohol - Rubbing alcohol, paint remover, cements, cleaners
toxic alcohols - clinical presentation
anion gap and osmolar gap (know equations!!!)
interpretation of results for alcohol tox
Anion gap PLUS osmolar gap -Methanol toxicity -Ethylene glycol toxicity -Alcoholic ketoacidosis Osmolar gap WITHOUT anion gap -Isopropyl alcohol (acetone) toxicity
ethylene glycol PKs
Rapidly absorbed from the GI tract
Rapidly distributed throughout the body
t ½ = 2.5-4.5 hrs In the presence of normal renal function; 20% excreted unchanged in the urine
Alcohol dehydrogenase in the liver is the first rate-limiting step in the breakdown
ethylene glycol phases of toxicity
1) 30 minutes to 12 hours post ingestion - CNS effects, nausea/vomiting, inebriation, lethargy/coma (within 4-8 hours), seizures
2) 12-24 hours post ingestion - Metabolic effects, cardiac compromise, anion gap acidosis***
3) 2 to 3 days post ingestion - Renal effects (calcium oxalate crystals), ATN within 12-48 hours
ethylene glycol toxicology tidbits
Presence of osmolar gap?
Ethylene glycol, methanol and ethanol serum concentrations
Wood’s lamp evaluation of urine
methanol: PKs
t1/2 = 14-30 hrs, peak levels in 20-90 min
Oral ingestion, inhalation, or dermal absorption
Metabolized by alcohol dehydrogenase to formaldehyde then to formic acid - Reaction is slow, so delay in toxic metabolite formation
methanol phases of toxicity
1) Headache, dizziness, ataxia, confusion
2) During formic acid accumulation, Pronounced visual symptoms, Anion gap
ethylene glycol and methanol: general management
Non-Pharmacologic - Gastric lavage and aspiration if presents in less than one hour; Charcoal is NOT effective; Hemodialysis if: EG concentration greater than 100 mg/dL, Methanol concentration greater than 45 mg/dL, Refractory acidosis, Renal Failure, Symptomatic
Pharmacologic:
-Ethanol and fomepizole - Inhibition of alcohol dehydrogenase limits metabolism of ethylene glycol)
-Adjunctive therapy - Shunt metabolism toward nontoxic metabolites (Thiamine (EG), Pyridoxine (EG), Magnesium (EG), Folate (Methanol) )
-sodium bicarb: Large amounts may be necessary to maintain normal pH; Helps in conversion of formic acid to carbon dioxide and water
Correct hypocalcemia and hypoglycemia
ethanol therapy
Greater affinity for alcohol dehydrogenase
0.6 gm/kg IV bolus then 110 mg/kg/hr - If HD started, increase dose to 250-350 mg/kg/hr
Optimal blood ethanol concentration of 100-150 mg/dL
Side effects: phlebitis, altered mental status, hypoglycemia
fomepizole
to treat ethanol glycol and methanol tox
Dose
-15 mg/kg IV load followed by 10 mg/kg Q12H x 4 doses
-Need to increase to 15 mg/kg IV Q12H if continued
-Administer Q4H during
hemodialysis
Advantages: No CNS depression, ICU stay not required
Disadvantage - Cost?
isopropyl alcohol PKs
50-80% metabolized by alcohol dehydrogenase to acetone
t1/2 of isopropyl = 3 hrs; acetone = 10-20 hrs
Acetone eliminated via kidneys and lungs
Lethal dose greater than 400 mg/dL
Potency is double-strength ethanol
Peak levels 30 min after ingestion
isopropyl alcohol toxic effects
Prolonged CNS depression
Nystagmus or miosis
Ketonemia
Hemorrhagic gastritis
Elevated osmolar gap
Increased serum isopropanol concentrations
Bradycardia/hypotension at high concentrations
isopropyl alcohol treatment
Gastric lavage
Hydration
Correct electrolyte abnormalities
Hemodialysis - Lethal doses, Coma, Refractory shock
