Overdose/Toxicities

Categories:

General Side Effects
- Alpha-1 Antagonism (Norepinephrine)
  - Significant orthostatic hypotension/tachycardia
  - MC: Risperidone/Paliperidone, Clozapine, Thioridazine, Trazodone
- Dopamine receptor antagonist
  - Metoclopramide
    - For nausea and vomiting, may have EPS
- Histamine Antagonism (Histamine)
  - Sedation, appetite stimulation, weight gain
  - MC: Quetiapine (most sedating), Olanzapine (weight), Clozapine (weight), Thioridazine
- Muscarinic Antagonism (Acetylcholine)
  - Anticholinergic – Delirium, fever, tachycardia, flushing, dry mucus membranes, constipation, Confusion and hallucinations
  - MC: Olanzapine, Clozapine, Thioridazine, Chlorpromazine
- Side Effect Monitoring
  - EKG
    - Amitriptyline/TCAs
  - CBC
    - Clozapine (Agranulocytosis) weekly but not carbamazepine
  - Plasma levels
    - Lithium, valproate
  - Falls
    - TCAs and Benzos
  - Glucose
    - Clozapine after 6 months
  - Dextromethorphan (cough syrup)
    - Dissociative symptoms and hallucinations
    - Add Quetiapine to treat Pseudobulbar Affect

Sudden, sustained contraction of neck, mouth, tongue and eye muscles |
Benztropine
Diphenhydramine | | Akathisia** (Days to weeks)** |
Subjective inner restlessness, inability to sit still, wanting to walk off
Dose dependent |
Benzodiazepine (Lorazepam)
Low-Dose BB (Propranolol)
Benztropine | | Parkinsonism** (Weeks to months)** |
Gradual-onset tremor, rigidity and bradykinesia |
Benztropine≥
Amantadine
Trihexyphenidyl | | Tardive dyskinesia** (4 months)** |
Gradual onset after prolonged therapy (≥6m): dyskinesia of mouth, face, trunk, extremities |
Valbenazine
Deutetrabenazine
Switch to Clozapine or Quetiapine |
Acetaminophen Overdose
- Gastroenteritis (non-specific) within hours, hepatoxicity within 1-2 days
  - Leading cause of hepatic failure in US
- Treatment
  - Activated Charcoal and N-Acetylcysteine
  - Liver Transplant
Alcohol Intoxication
- Slurred speech, incoordination, unsteady gait, attention/memory impairment, stupor, nystagmus
Alcohol/Methanol Overdose
- Anion Gap Metabolic Acidosis
- Fomepizole
  - Inhibits alcohol dehydrogenase
Alcohol Ketoacidosis
- Slurred speech, unsteady gait, altered mentation
- High Osmolar gap
- Increased anion gap
- Metabolic acidosis due to ketosis
Alcohol Withdrawal
- Symptoms
  - Tachycardia, diaphoresis, anxiety, hallucinations, Seizures
    - Macrocytic anemia
  - Mild (6-24h) – anxiety, insomnia, tremors, diaphoresis, palpitations, GI upset, intact orientation
  - Seizures (12-48h) – single or multiple generalized tonic, clonic
  - Alcoholic hallucinosis (12-24h) – visual, auditory, or tactile; intact orientation
  - Delirium Tremens (48-96h) – unstable vitals, hallucinations, confusion
- Withdrawal Prophylaxis
  - Chlordiazepoxide, Diazepam (medium-acting)
- Treatment
  - IV Lorazepam ≥ Chlordiazepoxide
    - Especially in Liver disease
  - IVF, Thiamine, Folate
    - Thiamine prior to glucose
Anticholinergic Poisoning
- Treatment
  - Physostigmine (cholinesterase inhibitors)
Arsenic Poisoning
- Mechanism
  - Binds to sulfhydryl groups
  - Disrupts cellular respiration and gluconeogenesis
- Sources
  - Pesticides, insecticides
  - Contaminated water, often from wells
  - Pressure-treated wood
  - Miners, smelters
- Clinical
  - Acute: Garlic breath, vomiting, watery diarrhea, QTc prolongation
    - Dehydration secondary to vomiting and diarrhea
    - Seizure, delirium, coma, torsades de pointes
    - Acute tubular necrosis
    - Painful paresthesia, ascending weakness
  - Chronic: Pigmentation, hyperkeratosis, stocking-glove neuropathy
    - Cancer: Skin, bladder, kidney, and/or lung
  - Mees Lines (Leukonychia striata) on the nails (hypo/hyperpigmented)
- Diagnosis: Elevated urine Arsenic Levels
- Treatment
  - IM Dimercaprol (British anti-Lewisite)
  - DMSA (meso-2,3-dimercaptosuccinic acid, Succimer)
Barbiturate Overdose
- Phenobarbital
- Weak Acids
- Treatment
  - Secure airway
  - Enhance elimination with Sodium Bicarbonate
    - Alkalinization of the urine
Benzodiazepine Overdose
- Only Benzos = CNS depression with normal vitals
  - Altered LOC, ataxia, slurred speech
- Benzos + Alcohol = CNS depression with abnormal vitals
  - Alcohol will cause bradycardia, hypotension, respiratory depression, hyporeflexia
- Treatment
  - RR Normal (12-20)
    - Supportive Treatment
  - Emesis, Lavage, Charcoal
  - 1 Time Acute Overdose
    - Flumazenil
      - Avoid Flumazenil if chronic benzo user
      - Partial agonist, may precipitate withdrawal/seizures
      - Fixes CNS depression, less effective for respiratory
      - SE: Re-sedation, hypotension, hypertension, seizures in long term users, arrhythmias, angina
Beta Blocker Overdose
- Bradycardia, AV block, and diffuse wheezing in a CAD patient
- Drowsiness, fatigue, depression, Bradycardia, Torsade de points, worsening HF, hypertriglyceridemia, bronchoconstriction, ED, Weight gain
- Treatment
  - Hypotension: IV Glucagon
  - Atropine, IV fluids
Carbon Monoxide Poisoning
- Treatment
  - 100% O2
  - Hyperbaric Oxygen if CO is ≥25-40%
    - Lower if pregnant
Cocaine Toxicity
- Inhibits norepinephrine reuptake into the sympathetic neuron (potentiating sympathomimetic actions)
  - Alpha and beta receptor stimulation results in coronary vasoconstriction and increased HR, Systemic BP, and Myocardial O2 demand
  - Enhances thrombus formation by promoting platelet activation and aggregation
- Age <30 w/o FH, severe or malignant hypertension, resistant hypertension, sudden rise in BP
- Sympathetic hyperactivity
- Symptoms
  - Personality/mood changes, sleep loss, weight loss, financial difficulties
  - Chest pain, epistaxis, rhinitis, headaches
    - Cocaine-related Chest Pain (CRCP)
      - Can occur due to non-cardiac causes (hemorrhagic alveolitis, pneumothorax)
  - Hypertension, tachycardia, dilated pupils, psychomotor agitation, tremors
- Complications
  - Seizures, Acute MI, Aortic Dissection, Intracranial hemorrhage
- Diagnosis: Urine Drug Screen
- Treatment of NSTEMI/Chest Pain:
  - Benzodiazepines for BP and Anxiety and O2 (lorazepam, diazepam)
    - Reduce sympathetic outflow (alleviate tachycardia, hypertension)
    - +/- Phentolamine if above doesn’t work
  - Aspirin
  - Nitroglycerin and CCBs for pain
  - Beta blockers are contraindicated
    - Would worsen coronary vasoconstriction (unopposed alpha-adrenergic stimulation)
  - No fibrinolytics
  - +/- Immediate Cardiac Catheterization
Cyanide Accumulation and Cyanide Toxicity
- Cyanide is a potent inhibitor of cytochrome oxidase-a3 in the mitochondrial ETC
  - Inhibits cellular respiration
- RF: Smoke inhalation (Mc toxicity in house fires)
  - Up to 90% of pts in house fires, only 35% have CO poisoning
  - Sodium Nitroprusside for hypertensive emergency
    - Prolonged use can lead to toxicity
    - More common in patients with renal insufficiency, signs of CHF
    - Onset is ~14-24 hours
- Symptoms
  - Skin: Flushing before cyanosis
  - CNS: HA, AMS, seizures, coma, confusion, agitation
  - CV: Arrhythmias
  - Resp: Tachypnea followed by respiratory depression, Pulmonary edema
    - BP instability
  - GI: Pain, nausea, vomiting
    - “Almond like” odor to the breath
  - Renal: Metabolic acidosis (lactic acidosis), Renal failure
    - Bright red venous blood (elevated ventral venous oxyhemoglobin saturation
- Treatment
  - Decontamination
    - Dermal
      - Remove clothing
    - Ingestion
      - Activated charcoal
    - Antidotes
      - 1) Hydroxocobalamin
        
        Removes cyanide from mitochondrial respiratory system
      - 2) Sodium Thiosulphate
        
        Slower onset, can’t be given with #1 or through the same catheter
      - 3) Sodium Nitrite
        
        Only if ingested
        
        Can’t be used in house fire victims due to synergistic effect with CO
  - Respiratory
    - No mouth-to-mouth resuscitation
    - Use supplemental O2/intubation
Digitalis Toxicity
- Blocks na/k ATPase in myocardial cells
  - Leading to influx of calcium, increased contractility, increased SV
  - Prolongs refractory period reducing ventricular rate
- Features
  - Characteristic ST depression with concave-up morphology “hockey stick”
  - AKI w/hyperkalemia and increased creatinine
  - Pain, nausea, vomiting
  - Confusion
  - Yellow halos around light, scotomas, blindness
Ethylene Glycol Ingestion
- Symptoms
  - Flank Pain, hematuria, oliguria, cranial nerve palsies, tetany
- Labs
  - High Osmolar gap
  - Increased anion gap
  - Metabolic acidosis
  - Calcium oxalate crystals in the urine
- Treatment
  - Fomepizole or Ethanol
Heparin
- Treatment
  - Protamine
Isopropyl Alcohol Ingestion
- CNS depression, deconjugate gaze, absent ciliary reflex
- High Osmolar gap
- No Increased Anion Gap
- No Metabolic acidosis
- Treatment
  - Supportive Care
Malignant Hypertension (Hypertensive Crisis)
- Binds to RYR1R causing CA2+ release.
  - MAOI + tyramine or stimulant
    - Prevents breakdown of tyramine in gut
    - Enhances peripheral NE effects increasing BP
- Symptoms
  - Headache following a meal (tyramine)
  - Hypertension, sweating, HA, vomiting
  - Sympathomimetic effect (hypertension)
- Labs
  - Increased BUN
- Complications: Stroke, intracranial bleeding, death, rhabdomyolysis
- Treatment
  - Stop agent
  - IV phentolamine
  - Dantrolene
  - Nifedipine can be helpful
- Thyroxine (T4) is treated with IV thyroxine for myxedema
  - Coma required more
Methanol Ingestion
- Visual Blurring, central scotomata, afferent pupillary defect, altered mentation, epigastric pain, hyperemic optic disc
- High Osmolar gap
- Increased anion gap
- Metabolic acidosis
- Treatment
  - Fomepizole (inhibits the alcohol dehydrogenase that converts methanol to formaldehyde)
  - Ethanol
Methemoglobinemia
- Formed by the oxidation of ferrous to ferric iron in hemoglobin
- Left shirt in the O2 curve because ferric iron cannot bind oxygen and this o2 binds tighter to ferrous iron in hemoglobin
- Functional anemia
- Causes: Dapsone, nitrates, topical/local anesthetics
- Treatment
  - Methylene Blue
Neuroleptic Malignant Syndrome (NMS)
- Antagonism of Dopamine (D2) receptors in the nigrostriatal pathway
  - Can occur with every class of antipsychotics
- Symptoms
  - Slow onset, clouding of consciousness (over 1-3 days w/delirium being the 1st symptom)
  - Fever ≥104F, confusion, delirium or catatonia
  - Muscle rigidity (Lead-pipe), General muscle rigidity
  - Autonomic instability (Tachypnea, hypertension, tachycardia, dysrhythmia)
  - Abnormal vitals, sweating, mydriasis
- Labs
  - Increased CPK, LFTs, WBCs
  - Myoglobin in urine
- Treatment
  - Stop antipsychotics or restart dopamine agents
  - Antipsychotic meds
  - May have increases Creatine Kinase and WBCs
  - IV fluids, supportive care; ICU
  - Benzodiazepines
  - Dantrolene (skeletal muscle relaxant) or bromocriptine (dopamine agonist), amantadine (dopamine agonist) if refractory
Opioids
- Treatment
  - Buprenorphine
    - Partial mu agonist, kappa antagonist
    - Treats withdrawal and chronic pain
    - Combined with naloxone (blocks receptor)
  - Naltrexone
    - Treats dependence, not withdrawal
  - Methadone
    - Treats withdrawl
Organophosphate Toxicity
- Excessive salivation, miosis, lacrimation, diarrhea, emesis, urination, bronchospasm
- Bradycardia, heart block, prolonged QTc
- Treatment
  - Pralidoxime
    - Reverses muscle paralysis (nicotinic effects)
  - Atropine
Phencyclidine (PCP) Overdose
- NMDA and Ach Antagonism
  - Particularly in the hippocampus and limbic system
- Dopamine, norepinephrine, and serotonin receptor activation
- Sigma receptor complex activation causing psychotic and anticholinergic effects
- Lasts <8 hours
- PCP withdrawal
  - Depression
- Ketamine is shorter acting
- Vertical or horizontal nystagmus, ataxia, violent behavior, hyperthermia, disorientation, delusions, muscle rigidity
- Treatment
  - Psychomotor Agitation: Parenteral Benzodiazepines (lorazepam, diazepam) ≥ Haloperidol unless seizure disorder is present
    - B52 – Haloperidol, diphenhydramine, and benzodiazepine
Phenytoin Toxicity
- Vertical Nystagmus
  - Cerebellar-vestibular system affected
  - Sedation, hypotension, arrhythmias, GI disturbances
  - Gingival hyperplasia and hirsutism if long-term use
- 2nd line anticonvulsant (after lorazepam) in treating status epilepticus
- Decreases repetitive firing of neuronal action potentials by slowing the rate of recovery of voltage gated sodium channels from inactivation
- SE: SJS
Salicylate Poisoning
- Treatment
  - Gastric Lavage, Activated charcoal, alkalinization of the urine, diuresis, dialysis
Serotonin Discontinuation Syndrome
- RF: SSRIs with short half-life and no active metabolites
  - MC with short half-life SSRIs (paroxetine ≥ venlafaxine)
- Onset within 3 days of discontinuation, resolution within 1-2 weeks
  - Fatigue, insomnia, myalgias from abrupt discontinuation in 20%
  - Headaches, anxiety, agitation
  - “Weird” sensations along arms and legs, “electric-shock-like” sensations in head/neck, “rushing” sensations in the head
  - Vertigo, tremor, ataxia
- Treatment
  - Restart drug and taper gradually over several weeks (6-8 weeks)
  - If persistent, switch to Fluoxetine
Serotonin Syndrome (SS)
- General
  - Over stimulation of 5-HT receptors in the central grey nuclei and the medulla
    - MC with stopping sertraline and fluvoxamine
    - Fluoxetine has a long half-life, must be quit 5 weeks prior to MAOI, but doesn’t need to be tapered
      - Tramadol (Ultram)
      - Serotonergic analgesic + SSRIs
- Symptoms
  - Activity (hyperactivity, hyperreflexia, hypertonia, tremor, seizure)
    - Myoclonus, Lower extremity rigidity, tremor
  - Autonomic (hyperthermia, diaphoresis, diarrhea, mydriasis)
    - Flushing, Tachycardia, hypertension
  - Agitation (Need AMS)
    - Anxiety, confusion, hypomania, coma
  - Headaches, N/V/D, dizziness and fatigue when suddenly stopping
- Exam
  - Hyperreflexia and myoclonus
  - Diaphoresis, hypertension, tachycardia
  - Fever/Hyperthermia, cardiovascular collapse
- Labs
  - No CPK or liver enzyme changes
- Treatment
  - Discontinue serotonergic meds, supportive, benzodiazepines, cyproheptadine
  - Cyclobenzaprine
  - Cyproheptadine (H1 receptor antagonist)
    - Weakly cholinergic hypotension
Steroids
- Glucocorticoids/Prednisone (Asthma/Lupus)
- Delusions/hallucinations. Alert and cognitively intact
- Anxiety, depression, psychosis, mania rarely
- Usually occur during the first week but may occur at any time
Tardive Dyskinesia
- 98% get worse with acute cessation of antipsychotic
  - D2 receptor upregulation and super sensitivity
  - Chronic blockade of dopamine receptors causes this
- Treatment
  - Switch from risperidone to clozapine (atypical antipsychotic)
  - VMAT2 Inhibitors
    - Blocks presynaptic dopamine release
      - May cause depletion of dopamine in synaptic cleft causing depression
    - Deutetrabenazine (Austedo)
      - TD and Huntington’s
    - Valbenazine (Ingrezza)
    - Reserpine
TCA (Tricarboxylic Acid) Overdose
- Features
  - Antihistamine Effects
    - Drowsiness, delirium, coma, seizures, respiratory depression
  - Anticholinergic Effects
    - Dry mouth, blurred vision, mydriasis, urinary retention
    - Flushing, hyperthermia
  - Hypotension, sinus tachycardia, prolonged PR/QRS/QT, Arrythmias
    - QRS ≥ 100ms is MC EKG abnormality
  - 1500mg for ≥4 hours = death
- Treatment
  - O2 and intubation, EKG monitoring
  - IV fluids
  - Activated charcoal if within 2 hours of ingestion (unless ileus present)
  - Seizures: Benzodiazepines
  - QRS ≥100: IV Sodium Bicarbonate
    - Therapy for QRS widening or ventricular arrythmia
    - QRS ≥ 100msec is associated with increased risk of arrhythmias and/or seizures
    - Cardioprotective and helps metabolic acidosis
Theophylline Toxicity
- Toxic form reduced clearance or decreased metabolism in the liver
- CNS Stimulation (headache, insomnia, seizures), GI (Nausea, vomiting), and cardiac toxicity (arrhythmia)
- Measure theophylline levels
tPA
- Treatment
  - Aminocaproic Acid
Warfarin
- Treatment
  - Vitamin K, FFP

Overdose/Toxicities

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