Toxicology Flashcards
1
Q
Assessing a Patient when suspicious for o/d
A
First Steps – ABCD3EF
- ABCs
- Intubation and mechanical ventilation as needed
- D3
- Disability assessment - neurologic exam/pupils/level of consciousness
- Empiric Drug therapy – oxygen, dextrose, naloxone (AMS)
- Initial Decontamination – ocular/dermal/GI decontamination
- E.F.
- E – ECG
- F – Fever/Temperature
2
Q
Toxicokinetics & Toxicodynamics
A
- Evaluate ADME
- Evaluate effects to body by toxic substances
- Toxic effects may be different from therapeutic action
- Slowed absorption
- Formation of poorly soluble concretions in GI tract (Bezoar)
- Slowed GI motility
- Toxin-induced hypo-perfusion
- Decreased protein binding
- Decreased elimination
- Saturation of biotransformation pathways
- Prolonged toxicity due to longer-acting metabolites
- End organ damage; Is the toxic substance renal/hepatic cleared
3
Q
GI Decontamination: Activated Charcoal (AC)
A
-
KEY: Decrease absorption and systemic exposure
- Effect occurs in the GI tract
- Toxin forms a complex with activated charcoal
- Indication
- Toxin known to be absorbed
- Within 1 hour of ingestion
-
After 1 hr. (Up to 4 hrs.) evaluate if:
- Prolonged gastric emptying
- Toxin properties
- Bezoar formulation
4
Q
AC Dosing
A
- Optimal dose based on minimum dose needed to completely absorb toxin – Ideal ratio of charcoal: toxin is ratio of 10:1
-
Flat Dosing
- Adolescents/Adults 50-100 grams (Will absorb 5-10 grams of toxin)
- Children 0.5-1 gram/kg
- When calculation of 10:1 ratio exceeds flat dosing, consider gastric emptying or MDAC
- Gritty texture, sticky and cakes
- Ideal to mix with water/juice
5
Q
AC Contraindications and AC Adverse Effects
A
- Clinically meaningful amount of toxin not absorbed
- Absent airway protective reflexes or not intubated
- GI perforation likely (caustic ingestions)
- Increased risk and severity of aspiration (hydrocarbons with high aspiration potential)
- Endoscopy anticipated (caustics)
AE:
- GI effects
- Constipation, nausea, fullness
- Vomiting ~20%
- Some studies show no difference compared to control group
- Greater when administered with sorbitol or via NG tube
- Greater after rapid ingestion of larger doses
- Pulmonary Aspiratory
- Misplaced tubed - aspiration of gastric contents and instillation into lungs
- Lower incidence in intubated patient
6
Q
Multi-Dose Activated Charcoal (MDAC)
A
Sequential doses of AC; Same contraindications/adverse effects
KEY:
- Prevent ongoing absorption if toxin persists in GI tract
- Enhance elimination in post-absorptive phase – interrupt enterohepatic recirculation of medications
-
Dosing regimens are individualized
- 0.5 grams/kg or 25-50 grams Q4-6 hours up to 12-24 hours
-
Benefits
- Life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, salicylates or theophylline
- Enterohepatic or enteroenteric recirculation and adsorbed by AC
- Toxin persists in GI tract
7
Q
Gastric Lavage
A
- KEY: Remove toxic potential before absorption
- Not indicated in all situations – evaluate risks & benefits
- Utilized with potentially life threatening amount
- Especially if within 60 minutes of ingestion
- Place orogastric tube
- Wash out gastric contents through repetitive instillation and withdrawal of fluid
Lavage Not Indicated
- Limited toxicity at almost any dose of toxin
- Well adsorbed by activated charcoal
- Amount ingested not expected to exceed adsorptive capacity
- Significant spontaneous emesis has occurred
- Patient presents many hours post-ingestion with minimal signs/symptoms of poisoning
- Highly efficient antidote available
Lavage Contraindications
- Respiratory
- No airway protective reflexes
- Not intubated
- High aspiration potential in absence of intubation
- GI
- Patient at risk of hemorrhage or GI perforation
- Toxin
- Alkaline caustic agent
- Foreign body
- Too large to fit into lavage tube
Lavage Adverse Effects
- Injury to esophagus and stomach
- Electrolyte imbalances
- Significant decreases in calcium and magnesium
- Severe hypernatremia
- Respiratory failure
- Aspiration pneumonitis
8
Q
Whole-Bowel Irrigation (WBI)
A
Purging GI tract to achieve gut clearance and prevent further absorption
- Oral or NG administration of PEG solution
- 1-2 Liters/hour
- Continue until rectal discharge clear
- Indications
- Toxic ingestion of SR tablets and metals
- Ingestion of illicit drug packets (drug smuggler)
- Toxin has slow absorptive phase
- Not absorbed by activated charcoal
- Other methods are not safe or beneficial
Irrigation Contraindications:
- Inadequate airway protection
- GI tract not intact
- Significant GI bleed
- Obstruction
- Uncontrolled vomiting
- Signs of leakage from cocaine packets (surgical removal)
- Do not administer with activated charcoal
- Administered AC after irrigation
9
Q
Syrup of Ipecac
A
- Not Recommended
- Was utilized to induced vomiting
- Contraindicated with caustics and corrosives
- Contraindicated if no gag, lethargy, comatose, seizing
- Has not shown to be of benefit
10
Q
Enhanced Elimination
A
- Diuresis
- If toxins eliminated primarily by kidneys
- Monitor fluids and electrolytes
- Urine alkalization for weak acids
- Sodium bicarbonate bolus followed by continuous infusion
- 1.5 - 2x maintenancerate
- Complications - Alkalemia, Hypokalemia
11
Q
Hemodialysis
A
- Especially if symptoms persist or worsening clinical status
- Corrects fluid/electrolyte imbalance
- Enhances removal of some toxic metabolites
- Molecular weight, water solubility, protein binding, distribution
- Large Vd – hemodialysis may be ineffective
-
If dialyzable
- Effective: Salicylates, ethanol, phenobarbital, lithium, VPA, phenytoin
- Ineffective: Amphetamines, antidepressants, antipsychotic agents • CCB, digoxin
12
Q
Supportive Therapy in OD
A
- Agitation
- Short acting benzodiazepines
- Antipsychotic agent (haloperidol or olanzapine)
- Delirium
- Agitation with abnormal vital signs: benzodiazepines
- Normal vital signs: haloperidol
- Seizures: short acting IV benzodiazepines
- Hyperthermia: external cooling; control agitation
- Hypotension: fluid bolus, inotropic agents
- Bradycardia: atropine
- Manage cardiovascular complications
- Rhabdomyolysis – Adequate hydration to maintain urine output
- Hemodialysis may be required
13
Q
Antidotes
A
- Acetaminophen - N-acetylcysteine
- Benzos - Flumazenil
- B-Adrenergic antagonists (B-blockers) - Glucagon
- CCBs - Calcium, High-dose insulin euglycemia, IV lipid
- Coumadin - Vit K
- Cyanide - Hydroxocobalamin, sodium nitrate and sodium thiosulfate
- Digoxin - Digoxin immune Fab
- Ethylene glycol - fomepizole, ethanol
- Iron - deferoxamine
- Isoniazid - pyridoxine
- Lead - British anti-Lewisite
- Organophosphorus insecticides and nerve agents - atropine, octreotide
- Tricyclic antidepressants - Sodium bicarb, IV lipid
14
Q
Acetaminophen Metabolism
A
- ~95% hepatic conjugation to inactive metabolites eliminated in urine
- Glucuronidation and Sulfation
- ~5% oxidized to reactive toxic intermediates
- CYP2E1 and CPY3A4
- Forms end product NAPQI (N-acetyl- p-benzoquinoneimine)
- Glutathione (GSH) quickly combines with NAPQI via GSH Conjugation
- Complex converted to nontoxic conjugate eliminated in urine
15
Q
Tylenol: Assessing Risk of Toxicity
A
Acute vs. Chronic
- 7.5 g or 150 mg/kg – lowest acute dose capable of causing toxicity
- 12 grams or 200 mg/kg – will cause hepatotoxicity
PK
- Time to peak may be delayed by food and co-ingestion of opioids or anticholinergics
- ER formulations has a delayed absorption; ~4 hours
- Assess laboratory findings - LFTs, PT/INR, glucose, SCr
- Assess signs and symptoms; Patient history
- How much (how many, what strength); How long ago;
- Assess APAP serum level compared to time of ingestion
16
Q
Rumack-Matthew nomogram
A
- Define earliest possible ingestion time
- Patients with levels below treatment line do not require further evaluation or treatment
- Early levels before 4 hours only rule out APAP ingestion
- Repeat if level is detectable
- “Nomogram Crossing”
- Occurs more commonly with extended release
- IV Acetaminophen -New lower line at 50 mcg/mL ??
17
Q
APAP OD: Special Situations
A
IF ingestion time is > 24 hours
- Assess APAP level and AST concentration; if AST high, then treat
Chronic Overdose
- Assess AST/ALT levels; APAP level
- Assess risk factors
- S/S;
- Chronic INH ingestion; malnutrition, anorexia
- Risk of increased NAPQI formation or decreased GSH stores
- Drug Interactions (APAP is metabolized to NAPQI by CYP2E1)
- Inducer will increase risk of hepatotoxicity
18
Q
APAP OD: Management
A
- Gastrointestinal decontamination
- Generally not recommendation due to very rapid GI absorption
- Supportive care
- Control N/V
- Manage hepatic injury
- Hypoglycemia
- Coagulopathy
- Manage renal injury
- Administer Antidote N-acetylcysteine
- Nearly 100% effective if started within 6-8 hours post ingestion
- Before glutathione stores are depleted to ~30% of normal
- NAC1 augments sulfation
- NAC2 is a GSH precursor
- NAC3 is a GSH substitute
- NAC4 improves multi-organ function during hepatic failure and may limit extent of hepatocyte injurt
- Nearly 100% effective if started within 6-8 hours post ingestion
19
Q
NAC Routes of Administration
A
- Equally efficacious IV or PO
- Consider rate of adverse events
- Mild reactions overall
- n/v 20% PO; 7%IV
- Anaphylactic reactions ~14-18% IV
- Cost - Drug versus Hospital stay
-
IV preferred if:
- Fulminant hepatic failure
- Inability to tolerate PO (AMS)
- APAP poisoning in pregnancy??
20
Q
NAC Dosing
A
Oral (Mucomyst):
- 140 mg/kg loading dose
- 70mg/kg q4 x 17 doses
- Total 1330 mg/kg in 72 hours
- Diluted and mix with juice or soda 3:1 ratio
Intravenous (Acetadote):
- 150 mg/kg (max 15 grams) infused over 1 hour
- 50 mg/kg (max 5 grams) infused over 4 hours
- 100 mg/kg (max 10 grams) infused over 16 hours
- Total 300 mg/kg in 21 hours
21
Q
Salicylate OD
A
Salicylate pharmacokinetics
- Available in a variety of OTC products
- Rapidly absorbed from stomach
- T1⁄2 for aspirin and salicylate metabolite
- Antiplatelet doses ~2-3 hours
- Anti-inflammatory doses ~12 hours
- • Hepatic transformation and Renal elimination
- Protein binding ~90% (decreased in overdose)
Altered PK in overdose
- Decrease in protein binding due to saturated binding sites
- Longer half-life
- Elimination pathways become saturated = increase in tissue/brain concentrations
22
Q
Salicylate OD Clinical Manifestations
A
Clinical Manifestations
-
Early s/s:
- GI irritation/N/V
- Direct central respiratory stimulation leads to hyperventilation and respiratory alkalosis
- Develops into mixed acid-base disturbance with respiratory alkalosis plus metabolic acidosis — Severe if respiratory acidosis develops
- Neurological most visible and concerning
- Confusion, lethargy, cerebral edema, coma
- Difference in CSF and serum glucose; CSF decreased by 33%
23
Q
Salicylate Analysis
A
- Determining Serum Levels via Trinder assay
- Watch your units - US mg/dL (mg/L and mcg/mL)
- Therapeutic level 10-30 mg/dL
- Toxic levels > 30 mg/dL
- Correlation between levels and toxicity variable and dependent on pH and could be misleading
- Acidemia = more salicylate has crossed into CSF/tissues
24
Q
Salicylate OD Management
A
- GI Decontamination
- AC reduces absorption ~50-80%, sooner better
- 10:1 ration of AC to ingested salicylates
- In massive ingestion, multiple doses (MDAC) to achieve desired ratio – efficacy debatable
- Fluids
- Need only to correct for fluid and electrolyte disturbances
- BUT no forced diuresis
- Increasing diuresis may lead to hyperventilation, vomiting, hyper-metabolic state
- Enhance Elimination with Serum and Urine Alkalinization
- Sodium Bicarbonate IV
- IV Bolus, followed by continuous infusion
- 132 mEq/L D5W at 1.5 – 2x maintenance rate
- Goal: maintain urine pH at 7.5-8
- Monitor
- Hypokalemia and hypocalcemia
- Supportive care
- Hemodialysis is an option
25
Salicylate OD: When should HD be considered..
* Kidney failure
* Acute Respiratory Distress Syndrome
* Persistent CNS disturbances
* Progressive deterioration in vital signs
* Severe acid–base or electrolyte imbalance despite treatment
* Hepatic compromise with coagulopathy
* Salicylate concentration (acute) \>90 mg/dL
* Chronic poisoning in those with concerning symptoms regardless of salicylate concentrations
26
NSAID OD
**NSAIDs**
* Highly protein bound
* Plasma t1⁄2 range from 1-2 hours to 50-60 hours
* Undergo hepatic metabolism w/ renal excretion of metabolites
**Overdose symptoms seen within 4 hours**
* Initial – mild and mainly GI (N/V/pain) and CNS (*drowsiness, headache, tinnitus, diplopia, dizziness*)
* Moderate/Severe – coma, seizures, CNS depression, metabolic acidosis, rhabdomyolysis, dysrhythmias, hypotension, electrolyte abnormalities, AKI; severe leads to multi-organ failure
**Management:**
* Supportive Care
* Children with \> 400 mg/kg are high risk of toxicity
* GI Decontamination
* Activated Charcoal should be considered first
* Massive OD - Gastric lavage followed by AC
* SR Formulations – Multiple doses of AC
* IV fluids, airway management, EKG
* Hypotension, electrolyte disturbances, conduction disturbances, unresponsive patients
* Dialysis for acid-base correction
27
Anticholinergic Agents OD
* Large number of medications possess anticholinergic properties
* Inhibit Acetylcholine (ACh) at muscarinic receptors producing the classic anticholinergic syndrome:
* “Red as a beet” – flushed skin
* “Hot as a hare” – hyperthermia
* “Dry as a bone” – dry mucous membranes
* “Blind as a bat” – blurry vision
* “Mad as a hatter” – confusion, delirium
**Management**
* Supportive care
* Agitation – Benzodiazepines; Antipsychotics
**Antidote for Anticholinergic effects – _Physostigmine_**
* Note: Do not use in TCA overdose due to exacerbation of cardiotoxicity
* Primarily used in medications that have anti-muscarinic properties (scopolamine, benztropine)
* **MOA** – Inhibits destruction of ACh by acetylcholinesterase
28
CALCIUM CHANNEL BLOCKERS and Β-BLOCKERS overdose
*Hypotension and Bradycardia*
**Management**
* GI Decontamination
* Especially if SR formulation
* Contraindications?
* Symptomatic or asymptomatic?
**Activated Charcoal**
* MDAC – efficacy in continuously absorbing SR formulation
**Supportive Care**
* EKG monitoring and continuous cardiac monitoring
* Intubation if necessary
* Focus on maintaining/improving cardiac output and peripheral vascular tone
29
Ca-Channel Blockers and Beta-Blocker overdose management
Step#1
* **Fluid boluses**
* Caution with aggressive fluid resuscitation
* **Atropine**
* Treatment of symptomatic bradycardia
* Improves heart rate and cardiac output
* Risks versus benefits??
* Decreases GI motility
* **Calcium**
* Increases extracellular calcium
* Improves blood pressure
* Caution with extravasation
* **Glucagon**
* Functions as “pure” β1 agonist with no peripheral vasodilatory effects
* Increases heart rate, contractility, and blood pressure
* ***Drug of choice for β-blocker overdose***
* Dosing - IV bolus, followed by continuous infusion
Step #2
* If non-responsive to Step 1 – move onto step 2
* Hyperinsulinemia-euglycemia therapy
* 20% IVFE
30
Insulin-Euglycemia Therapy/High-dose insulin euglycemia (HIE)
* Myocardial tissue becomes carbohydrate dependent for metabolic needs
* **Myocardium becomes insulin resistant**
* Improved contractility
* Calcium mediated insulin secretion from β-islet cells in pancreas inhibited by CCB
* Insulin bolus (w/dextrose unless glucose \> 300 mg/dL)
* Followed by Insulin infusion
* Monitor glucose q30 minutes x 4 hours
* What else should be monitored?
31
Lipid Emulsion 20%
* Activates ion channels including calcium
* Enhances intracellular metabolism
* Acts as lipid sink to sequester lipid soluble drugs
* Lowers free serum concentrations
* \*\*Highly lipophilic drugs benefit more
* Especially effective for CCB and propranolol
32
Antipsychotics
* Mild intoxication
* Sedation, hypotension, miosis
* Severe intoxication
* Agitation & delirium, seizures, cardiac arrhythmias, respiratory arrest, and coma
* Dystonias and pseudoparkinsonism may occur
* Treatment: supportive
* Gastric lavage, activated charcoal
* Hypotension; Seizures
* CV: Sodium bicarbonate
33
Neuroleptic Malignant Syndrome
* Life Threatening Emergency
* Cardinal symptoms
* T \>38 (100.4), altered level of consciousness, rigidity, autonomic dysfunction (tachycardia, labile BP, diaphoresis, tachypnea, or urinary/fecal incontinence)
* Risk factors: dehydration, physical exhaustion, organic mental disease
* Treatment: supportive care, dantrolene
* *Time to presentation – NMS develops more gradually compared to Serotonin Syndrome which has a rapid onset*
34
TCA OD
* Class 1A antiarrhythmic agents – lethal arrhythmias
* Treatment:
* **Sodium bicarbonate to displace TCA from cardiac Na++ channels**
* Torsade's – Magnesium Sulfate IV
* Must correct acidosis and hypoxia; hypotension
* CNS toxicity - Seizures
35
Carbon Monoxide (CO)
* Mechanism of toxicity:
* Binds to hemoglobin leading to carboxyhemoglobin (COHb)
* COHb CANNOT transport oxygen leads to decrease in oxygen delivery to cells
* Initially - Headache, dizziness, nausea, confusion
* Later -- Tachycardia, tachypnea, myocardia ischemia
* *Clinical Pearl: Many cases of CO toxicity arise in the winter time and are misdiagnosed as influenza due to atypical initial signs and symptoms \*\*Evaluate COHb level*
* *Normal Level (non-smoker): 0 – 5 %; (smoker): 6 – 10%*
**Management**
* 100% Oxygen!
* Administration of O2 will antagonize COHb
* Decreases half-life of CO from ~220 min at room air to ~80 min
* Hyperbaric oxygen (Hyperbaric Chamber)
* Treatment of choice in significant CO exposures
* Administration of 100% O2 under increased pressure
* Decreases the half-life of CO to ~ 40 min
• In NY - Hyperbaric Oxygen (HBO) Program at NewYork-Presbyterian Hospital
36
Chelating Agents
**Edetate calcium disodium (Calcium EDTA)**
* Indication: Lead poisoning
**Dimercaprol**
* Indication: Severe lead, arsenic, and mercury toxicity
**Succimer (Chemet®)**
* Indication: Lead, mercury, and arsenic exposures
37
Drug abuse: Dopamine’s Role in Reinforcement
* Prime target of addictive drugs: Dopaminergic Mesolimbic Tract
* Function: Arousal, memory, stimulus processing, motivational behavior
* Central role in Reward Processing -- increase the level of dopamine reinforcement and risk of psychosis
* Prime target of non-addictive drugs: Cortical and Thalamic circuits
* *Examples: LSD, PCP and ketamine*
* Substances that alter perception without feelings of reward/euphoria (feeding detached from reality)
* Can cause anxiety, memory loss, impaired motor function
38
Amphetamines “Club Drug”
* Smoked, injected, or swallowed
* Methylene-dioxymethamphetamine (MDMA) – Ecstasy; 3,4 Methylenedioxyamphetamine(MDA, love drug), Methamphetamine (speed, uppers); Cathinone (Methcathinone, MDPV, Mephedrone) - Bath Salts
* Lipophilic
* Hepatic versus renal
* Dependent on compound
* CYP1A2, CYP2D6\*, and CYP3A4
* Extensive renal elimination
**PK**
* Induction of catecholamine release
* Spills dopamine, norepinephrine, serotonin into synapse
* Stimulates α-adrenergic receptors, β-adrenergic receptors, dopamine, and serotonin
* Serotonin – primarily responsible for hallucinogenic and illusion properties
* Norepinephrine – primarily responsible for vasoconstriction and increased cardiac activity
* **Chronic administration** alters catecholamine transporter functions, depletes catecholamine and produces irreversible destructions of neurons
39
Inhalants
* **Nitrates, ketones, hydrocarbons**
* * “sniffed”: inhale from open container
* “huffed”: inhale cloth soaked with inhalant
* “bagged”: inhale bag filled with inhalant
* Highly lipophilic, stimulate GABAA
* **Initially**.. Euphoria, hallucinations (visual and auditory) • Headaches, dizziness
* **Toxicity**
* Slurred speech, confusion, tremor, weakness
* Seizures, coma, respiratory depression
* Dysrhythmias (poor prognosis)
* Hepatotoxicity, renal toxicity with electrolyte abnormalities
* Acute cardiotoxicity “sudden sniffing death”
* Inhalant “sensitizes the myocardium”
* Long term toxicity: white matter lesions seen in CNS
* Treatment of overdose -- Supportive therapy
40
Cannabinoids
Cannabinoids
* Exogenous cannabinoids
* Δ9-tetrahydrocannabinol (THC) -- Principle psychoactive
* Central and Peripheral Cannabinoid receptors (CB1 and CB2)
* Inhibit adenylyl cyclase and stimulate potassium channel conductance
* Affect acetylcholine, noradrenaline, dopamine
* *CB1 – affects regulation of cognition, memory, motor activities, nociception, N/V*
**Chronic exposure leads to dependence**
* Withdrawal - Mild and short
* Restlessness, irritability, insomnia, nausea
* Supportive therapy
* ***Cannabinoid Hyperemesis Syndrome***
* Abdominal discomfort, nausea, hyperemesis • Refractory to opioids and anti-emetics
* Hallmark of Syndrome:
* Immediate relief of symptoms with hot showers/baths • Leads to compulsive hot showers/baths
41
Nicotine
* Mimics effects of acetylcholine release
* Binds to nicotinic receptor (nAChR)
* Located in the brain, spinal cord, autonomic ganglia, adrenal medulla, neuromuscular junctions
* nAChR expressed on Dopamine neuron – dopamine released
* Clinical effects are dose-dependent
* Treatment of addiction
* Short-acting medication “relievers” (nicotine nasal spray, inhaler)
* Long-acting medication “controllers”
* Varenicline (Chantix)
* Partial nicotine receptor agonist
* Suicidal ideation is very concerning
* SE: N/V/C, vivid dreams, headache, insomnia
* Bupropion (under brand name Zyban)
* Lowers seizure threshold\*\* caution if history of seizures
**Nicotine Replacement Therapy (NRT)**
* **Patch**
* Apply to clean, dry, relatively hairless part; change locations daily • AE: Skin irritation, erythema, burning, insomnia
* **Gum/Lozenge can be added to patch**
* Do not eat or drink (except water) 15 min before or while using
* AE: Nausea or heartburn if swallowed
* **Gum Directions**
* Chew until peppery taste (~15 chews), park gum between cheek & gum; when taste diminishes, resume chewing until peppery taste again, then park gum in different area of mouth
* **Lozenge Directions**
* Rotate throughout mouth until dissolved; Do not chew or swallow
42
Binge Drinking
* Original Definition - 5 drinks in 2 hours (based on men)
* National Institute on Alcohol Abuse and Alcoholism (NIAAA) defined binge drinking as pattern of drinking that brings person’s blood alcohol concentration (BAC) to ≥ 0.08%
* Youth likely to reach higher BAC with 5 drinks in 2-hours
* Girls 9-17 yo & Boys 9-13 yo ≥3 drinks
* Boys 14-15 yo ≥4 drinks
* Boys 16-17 yo ≥5 drinks
43
Alcohol BAC Levels
* BAC of 50 to 150 mg/dL – Intoxication
* Consequence of alcohol entering bloodstream faster than it can be metabolized by liver
* Initial euphoria followed by incoordination, imbalance, ataxia, sleepiness, loss of social inhibitions, depression, and hostility
* BAC \> 150 mg/dL – More depressant symptoms
* Lethargy, bradycardia, hypotension, and respiratory depression
* BAC \> 450 mg/dL – Alcohol poisoning
* Stupor, coma, and death by respiratory depression with respiratory acidosis and hypotension
* Seizures - More common to occur in children with hypoglycemia
**Management**
* Supportive Care
* Benzodiazepine +/- haloperidol
* Intubation
* GI decontamination
* Recent ingestion, delayed absorption, concomitant ingestions
* Hypoglycemia
* Evaluate need for therapy (inpatient or outpatient)
44
Benzodiazepine Reversal
* Enhance GABAA receptor activity
* Dependence is common; addiction is rare
* Withdrawal (symptoms taper within 1-2 weeks)
* Occurs within days of discontinuation (depends on T1/2)
* Irritability, insomnia, phono- or photo-phobia, seizures
* Reversal of benzodiazepines: Flumazenil
* Shorter t1⁄2 compared to BZD – requires multiple doses
* Caution w/inducing abstinence/withdrawal syndrome
