Toxicology - Opioid,Benzodiazepine,Antidepressant,Toxic Alcohols Overdose Flashcards
Opioids Toxidrome and Clinical Presentation
Toxidrome:
Opioid
Clinical Presentation:
-Decreased mental status
-Pinpoint pupils
-Decreased bowel sounds
-Depressed respiration
Opioid Management and Antidote
Administer antidote (Naloxone)
Protect airway
Naloxone doses and routes of administration
IV, IM, IN
Non-opioid dependent: IV 0.4mg
Opioid dependent patient (heroin, oxycodone, etc. daily): IV 0.04mg and titrate to effect
Bystanders: IN 4mg (Narcan®)
Continuous Infusion: 1⁄2 initial effective bolus dose and 2/3 of effective dose per hour
Goal: Maintain respirations
Side effects: runny nose, flash pulmonary edema, [acute precipitated withdrawal]
Naloxone Induced Pulmonary Edema
Proposed mechanism: Adrenergic response, catecholamine surge
-Tachycardia, tachypnea, hypertension
Shift in blood volume into the pulmonary vasculature
-Pulmonary vasoconstriction, pulmonary hypertension, fluid leakage into lungs
Treatment: Nitroglycerin, diuretics, positive pressure ventilation
Prevention? Smaller initial doses of naloxone
Loperamide
Imodium - OTC anti-diarrheal. Inhibits intestinal peristalsis through μ-opioid receptor agonism
Toxidrome: Opioid
Clinical presentation: Opioid overdose, severe cardiac arrhythmias
Blood brain barrier: P-glycoprotein. Co-administration of PGP inhibitor enhances effects
Doses:
Therapeutic: 2 – 4mg PRN (max: 16mg/day)
Recreational: 30mg – 200mg (+)
Loperamide Management
Respiratory Depression: Naloxone
Cardiac disturbances:
-IV Magnesium
-Sodium Bicarbonate
-Intravenous Isoproterenol
-Transcutaneous Pacing
CPR and ACLS
Benzodiazepine Overdose
Facilitate GABA binding
Toxidrome: Sedative-Hypnotic
CNS depression
Drowsiness
Stable vital signs
-Mildly depressed respiratory drive
Treatment: Monitoring, supportive care
High therapeutic index
Lethality rare, would be from respiratory depression (like opioids)
Benzodiazepine Withdrawal
Symptoms:
́ Severe sleep disturbance
́ Irritability
́ Increased tension and anxiety
́ Panic attacks
́ Sweating
́ Difficulty in concentration
́ Dry retching and nausea
́ Palpitations
́ Headache
́ Psychotic reaction
́ Seizures
́ Death
Precipitated withdrawal is a concern in these patients! Lethal even more than opioid comparison
Benzodiazepine Antidote
Flumazenil
Dose: 0.2 mg IV over 15 seconds
Peds: 0.01mg/kg IV
Competitive antagonist at benzodiazepine receptor site
Onset: 1-2 minutes
Variable duration, redoing may be required
Use or not use? Benzo protectant effect, relatively non lethal component of toxicity. Precipitated withdrawal and potentially lethal seizures possible
Flumazenil does not completely or consistently reverse benzodiazepine-induced respiratory depression and may require using other supportive measures (e.g. Bag-valve mask ventilation, endotracheal intubation, etc.)
Polysubstance Overdose
Elimination (ex. activated charcoal)
Administer antidote (ex. N-Acetylcysteine)
Supportive Care (ex. Benzodizepines)
Safest Times to Use Flumazenil
-
Procedural Sedation
- Known PMH
- Iatrogenic benzodiazepine sedation -
Unintentional, pediatric exposure
- Relative confidence on non-benzodiazepine dependent child
- Minimizes extensive work up
Other proposed uses (None routinely recommended):
Hepatic encephalopathy
Z-drug overdose (e.g. Zolpidem)
Ethanol intoxication
Top 2 Antidepressant Classes/Agents for Overdose
Probably not a question for exam purposes
1. Bupropion
2. TCA
Tricyclic Antidepressant Agents (Reminder slide)
Amitriptyline
Nortriptyline
Doxepin
Imipramine
Desipramine
Tricyclic Antidepressant Toxicity - Toxidrome and Effects
Toxidrome: Anticholinergic
Catechol reuptake inhibitor and Alpha adrenergic blocker = Hypotension
GABA antagonist = seizures
Sodium channel blocker = dysrhythmias
Tricyclic Antidepressant Toxicity - Clinical Effects
Increased BP (initially) -> Decreased BP
Increased HR
Increased temperature
Normal to decreased HR
Rapid decline in mental status
EKG Interpretation- TCA Toxicity
Sensitivity 100%, specificity 98%
Terminal 40 msec rightward axis deviation in frontal plane (R wave in aVR)
QRS widening and increasing R wave amplitude
-higher/wider = higher risk of seizures
TCA Toxicity Treatment/Antidote
Sodium Channel Blockade is lethal component
Sodium alone may be effective (Hypertonic Sodium)
Alkalinization alone may be effective (Hyperventilation)
Sodium + Alkalinization
Hypertonic sodium bicarbonate
-Provides sodium for sodium channel blockade
-Alkalinization reduces TCA binding to its receptor in myocardium
Dose: 1-2 mEq/kg boluses
150 mEq in 1 L D5W at twice maintenance rate (~150-200 ml/hour)
Endpoints: QRS narrowing and Blood pH not >7.55
TCA Toxicity Other Treatments
Treat Anticholinergic effects: No treatment, tachycardia may be protective (because BP may lower, this preserves cardiac output)
Dysrhythmias: Magnesium, Lidocaine
Hypotension: Norepinephrine, Epinephrine, Vasopressin, Phenylephrine also Methylene Blue, Lipid Emulsion, High Dose Insulin
Seizures: Benzodiazepines, Barbiturates
Not Phenytoin (is a sodium channel blocker) - Increase frequency and duration of VT in TCA poisoned dogs
Not Flumazenil - Possible uncontrolled seizures and decreased ability to treat seizure
Physostigmine
Anticholinergic Toxidrome treatment
Case reports of asystole following administration in TCA overdoses
Bottom line: Do not use in TCA overdose!!
Bupropion (Wellbutrin, Zyban)
Toxidrome: Sympathomimetic
Unclear toxicology
-Delayed seizures in overdose setting (up to 24 hours s/p ingestion)
-Seizure risk doses >/ 600mg/day (hence MDD < 450mg/day)
-Wide complex dysrhythmias (widened QRS) - normally means sodium channel blockade, but not in this case because Not responsive to sodium bicarbonate
Decontamination
• Orogastric Lavage ; Activated Charcoal ; Whole bowel irrigation
Treatment: Supportive Care (seizure? hypertensive? —> Benzodiazepine), lipid emulsion, ECMO
Cases of
•Sympathomimetic crisis
•Cardiogenic shock
•Status epilepticus
•Lazarus effect (come back from dead)
•Death
SSRIs
Serotonergic features
-Altered mental status, tachycardia, myoclonus, tremors, diarrhea, seizures
Treatment: Supportive Care, Monitoring
(Es)Citalopram most likely to cause seizures
-ECG abnormalities may be delayed up to 24 hours
-May also widen QTc and QRS
Serotonin Syndrome
Causes:
-Polypharmacy
-Drug interaction
-Overdose of multiple serotonergic agents
-Most specific to 5HT2A and possibly 5HT1A
Clinical effects:
Spontaneous clonus, agitation, diaphoresis, hyperthermia, tremor, hyperreflexia, diarrhea, mental status changes, incoordination
Treatment:
- Supportive care: decreasing core temperature
- Antidote – Cyproheptadine 12mg PO followed by 4-8mg PO Q6H maintenance
-Is an antihistamine, antiserotonergic agent with anticholinergic burden potential
-Use is kind of controversial
- Other: **Benzodiazepines (mainstay therapy), propranolol
Anion Gap Calculation and Normal Range
Anion Gap = Na+ - (Cl- + HCO3-)
Normal gap ~ 4 - 12 (up to 16 if including K+)
MUDPILERS Acronym - What do these contribute to?
Increased Anion Gap Metabolic Acidosis
[which acid is contributing]
M - Methanol [Formic Acid]
U – Uremia [Urea]
D – DKA,SKA,AKA [Ketoacids]
P – Phenformin (metformin), Paraldehyde [Lactate]
I – Isoniazid, INH [Lactate]
L – Lactate, CO, CN, MetHb [Lactate]
E – Ethylene Glycol [Glycolic Acid]
R - Rhabdomyolysis
S – Salicylates [Ketoacids / Lactate]
