Rosen & Barkin's 5-Minute Emergency Medicine Consult (456 page)

• Primarily for depression
  
• Selegiline, a selective monoamine oxidase B inhibitor, is sometimes used to treat Parkinson disease, and also comes in a transdermal preparation.
  
• Monoamine oxidase inhibitor (MAOI) pharmacologic actions:
  
  • Disruption of equilibrium between endogenous monoamine synthesis and degradation, resulting in:
    
    • Increased neural norepinephrine levels
      
    • Downregulation of several receptor types
      
  • Inhibition of irreversible (noncompetitive) enzyme
    
  • Inhibition of other B
    ₆
    -containing enzymes
    
• MAO: Principal inactivator of neural bioactive amines:
  
  • MAO A:
    
    • Present in the gut and liver
      
    • Protects against dietary bioactive amines
      
  • MAO B:
    
    • Present in neuron terminals and platelets
      
    • Sympathomimetic amines: Types of bioactive amines
      

• MAOI overdose:
  
  • Toxicopharmacology poorly understood
    
  • MAO inhibitors: Amphetamine-like in structure:
    
    • Early: Indirect sympathomimetic effect
      
    • Late: Sympatholytic response (hypotension)
      
• MAOI hypertensive crisis syndrome:
  
  • Results from impaired norepinephrine degradation and large norepinephrine release precipitated by an indirect- or mixed-acting sympathomimetic agent
    
  • Common precipitants: Tyramine, cocaine, amphetamines
    
• Serotonin syndrome (SS):
  
  • Commonly results from exposure to combinations of agents that affect serotonin metabolism or action
    
  • Increases serotonin synthesis: Tryptophan
    
  • Increase serotonin release:
    
    • Indirect- and mixed-acting sympathomimetic agents and dopamine receptor agonists
      
  • Decrease serotonin reuptake:
    
    • Selective serotonin reuptake inhibitors
      
    • Tricyclic antidepressants
      
    • Newer antidepressants: Trazodone, nefazodone, venlafaxine
      
    • Phenylpiperidine opioids: Meperidine, dextromethorphan, tramadol, methadone, propoxyphene
      
  • Direct serotonin receptor agonists:
    
    • Buspirone, sumatriptan, lysergic acid diethylamide
      
  • Decrease serotonin breakdown:
    
    • MAOIs
      
  • Increases nonspecific serotonin activity:
    
    • Lithium
      

DIAGNOSIS

• MAOI overdose:
  
  • Delayed onset (6–12 hr)
    
  • Initial hypertension with headache
    
  • Hyperadrenergic activity:
    
    • Tachycardia
      
    • Hypertension
      
    • Mydriasis
      
    • Agitation
      
  • Neuromuscular excitation:
    
    • Nystagmus
      
    • Hyperreflexia
      
    • Tremor
      
    • Myoclonus
      
    • Rigidity
      
    • Seizures
      
  • Hyperthermia
    
  • Associated complications:
    
    • Rhabdomyolysis
      
    • Renal failure
      
    • Disseminated intravascular coagulation (DIC)
      
    • Acute respiratory distress syndrome (ARDS)
      
• MAOI hypertensive crisis syndrome (MAOI interaction with drug or food):
  
  • Hypertension
    
  • Tachycardia or bradycardia
    
  • Hyperthermia
    
  • Headache, usually occipital
    
  • Altered mental status
    
  • Intracranial hemorrhage
    
  • Seizures
    
• SS:
  
  • Increased neuromuscular activity
    
  • Increased deep tendon reflexes:
    
    • Lower extremity may be greater than upper
      
  • Tremor
    
  • Myoclonus
    
  • Rigidity (when severe)
    
  • Autonomic nervous system hyperactivity:
    
    • Hyperthermia
      
  • CNS:
    
    • Agitation
      
    • Hallucinations
      
    • Delirium
      
    • Coma
      
  • Diarrhea
    
  • SS vs. neuroleptic malignant syndrome (NMS):
    
    • Both present along a spectrum of severity (mild to severe)
      
    • Onset: Hours (SS) vs. days (NMS)
      
    • Gastrointestinal symptoms: May be present (SS) vs. absent (NMS)
      
    • Only drug/medication history may differentiate in many cases
      

• Time of ingestion
  
• Bottle available
  
• Intentional or accidental
  
• Coingestions
  

• Neuromuscular hyperactivity:
  
  • Myoclonus
    
  • Rigidity
    
  • Tremors
    
  • Hyperreflexia
    
• Autonomic hyperactivity:
  
  • Tachycardia or bradycardia
    
  • Fever
    
  • Diaphoresis
    
• Altered mental status:
  
  • Agitation, confusion, or excitement
    

• History of ingested substances
  
• Rectal temperature monitoring as indicated
  
• Blood pressure/cardiac monitoring
  

• Urinalysis:
  
  • Blood
    
  • Myoglobin
    
• Electrolytes, BUN/creatinine, glucose:
  
  • Hypoglycemia may contribute to altered mental status.
    
  • Acidosis may accompany severe toxicity.
    
  • Rhabdomyolysis may cause renal failure.
    
  • Hyperkalemia—life-threatening consequence of acute renal failure
    
• Coagulation profile to monitor for potential DIC:
  
  • INR, prothrombin time, partial thromboplastin time, platelets
    
• Creatinine kinase:
  
  • Markedly elevated in rhabdomyolysis
    
• Urine toxicology screen:
  
  • May be positive for amphetamines, given the structural similarities between some MAOIs and amphetamines
    
• Aspirin and acetaminophen levels if suicide attempt a possibility
  
• Arterial blood gas
  

• Chest radiograph:
  
  • ARDS
    
• Head CT if significant headache or altered mental status or focal neurologic signs:
  
  • Subarachnoid hemorrhage, intracerebral bleed
    

Lumbar puncture for:

• Suspected meningitis (headache, altered mental status, hyperpyrexia)
  
• Suspected subarachnoid hemorrhage and CT normal
  

• Hyperthermia:
  
  • Infection
    
  • Hyperthyroidism
    
  • Heat stroke
    
  • Anatomic thalamic dysfunction
    
  • NMS
    
  • Malignant hyperthermia
    
  • Malignant catatonia
    
  • Ethanol or drug withdrawal
    
  • Anticholinergic toxicity
    
  • Sympathomimetic overdose
    
  • Cocaine-associated delirium/rhabdomyolysis
    
  • Salicylate toxicity
    
  • Theophylline toxicity
    
  • Nicotine toxicity
    
• Hypertension:
  
  • Hypoglycemia
    
  • Carcinoid syndrome
    
  • Pheochromocytoma
    
  • Accelerated renovascular hypertension
    
  • Ethanol or drug withdrawal
    
  • Sympathomimetic toxicity
    

TREATMENT

• Patient may be uncooperative or violent.
  
• Secure IV access.
  
• Protect from self-induced trauma.
  

• Airway, breathing, and circulation (ABCs)
  
• IV access and fluid resuscitation if hypotensive
  
• Oxygen
  
• Cardiac monitor
  
• Naloxone, thiamine, D50W (or Accu-Chek) if altered mental status
  

• Gastrointestinal decontamination:
  
  • In potential life-threatening ingestions gastric lavage may be carefully considered if within
    1 hr
    of ingestion
    
  • Administer activated charcoal
    
• Hyperthermia:
  
  • Benzodiazepines if agitated
    
  • Active cooling if temperature >40°C:
    
    • Tepid water mist
      
    • Evaporate with fan
      
  • Paralysis:
    
    • Indicated if muscle rigidity and hyperactivity contributing to persistent hyperthermia
      
    • Nondepolarizing agent (e.g., vecuronium)
      
    • Avoid succinylcholine
      
    • Intubation; mechanical ventilation
      
  • Administer acetaminophen.
    
  • Apply cooling blankets.
    
• Severe, malignant hypertension:
  
  • Nitroprusside (for MAOI overdose)
    
  • Calcium-channel blocker or phentolamine (for MAOI + food interaction)
    
  • Use short-acting IV agent that can be rapidly “turned off.”
    
• Hypotension:
  
  • Initially bolus with isotonic crystalloid solution
    
  • If no response, administer norepinephrine.
    
  • Dopamine may be ineffective
    
• Dysrhythmias (premorbid sign in MAOI overdose):
  
  • Treatment based on dysrhythmia
    
• Seizures:
  
  • Benzodiazepines
    
  • Barbiturates if benzodiazepines unsuccessful
    
  • Pyridoxine for refractory seizures
    
• Rigidity:
  
  • Benzodiazepines
    
  • Paralysis with vecuronium, endotracheal intubation, and mechanical ventilation
    
• ARDS:
  
  • Oxygen
    
  • Intubation and positive end-expiratory pressure as indicated
    
• DIC:
  
  • Fresh-frozen plasma
    
  • Platelets
    
  • Whole-blood transfusions
    
• Rhabdomyolysis:
  
  • IV isotonic crystalloid solution
    
  • Maintain hydration to ensure adequate urine output
    
• Specific treatment for SS:
  
  • Mainstay: Supportive care, discontinuation of offending agents
    
  • Nonselective serotonin antagonist:
    
    • Cyproheptadine