Toxidromes

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Anticholinergic Syndrome

  • Physiology:Inhibition of muscarinic cholinergic neurotransmission (blocking acetylcholine from binding receptors) gives these drugs their effect. Receptors are found on smooth muscle in the GI tract, bronchi, heart, salivary and sweat glands, the cilliary body of the eye,
  • Drugs: antihistamines, sleep aids, tricyclic antidepressants, cold preparations, atropine, cyclopentalate (eye drops)
  • Plants: deadly nightshade (belladonna), jimson weed
  • Clinical Features:
    • “Red as beet’ – vasodilation
    • “Dry as a bone” – inhibition of sweat glands, dry axilla and groin, dry mouth.Dry mouth causing muffled voice.
    • “Hot as a hare” – lack of sweating and increased stimulation cause hyperthermia
    • “Blind as a bat” – blurry vision due to inability to constrict pupil and accommodate. Pupils get bigger when aroused and unopposed sympathetic stimulation present.
    • “Mad as hatter” – central muscarinic blockade causing delirium, hallucinations, psychosis, seizures. Picking at skin common.
    • “Full as a flask” – urinary retention due to detrusor muscle and urethral sphincter inability to relax.
  • Differential diagnoses not to forget:
    • Infection: meningitis, sepsis
    • Salicylate overdose
    • Withdrawal: benzodiazepines or alcohol
  • Treatment:
    • Decontamination (usually ingested not dermal, but just in case)
    • Supportive care: IV fluids, cooling, sedation, intubation
    • Seizures give benzodiazepines
    • Arrhythmias or long QT – consider sodium bicarb (consider TCA ingestion)
    • Physostigmine – inhibits acetylcholinesterase reversibly. 0.5 to 2 mg IV, 0.02 mg/kg IV for peds (max 0.5mg). Push slowly over 5 min. Repeat q 20-30 min. – Used if patient agitated and delirious, hold if otherwise. Relatively contraindicated in TCA overdose based on minimal evidence and cases of asystole.

Cholinergic Crisis

  • Physiology:Inhibition of acetylcholinesterase (AChE ) causes increased levels of acetylcholine. Symptoms arise from areas where receptors are found:  smooth muscle in the GI tract, bronchi, heart, salivary and sweat glands, the ciliary body of the eye. Primary effect is on the red blood cell AChE.
  • Drugs: Pesticides resulting in field workers exposed (dermal, inhalation) to sprayed chemicals.
    • Organophosphates – (diazinon, dursban, fenthion, malathion, parathion) causes inhibition of AChE enzyme the eventually become irreversible
    • Carbamates – (aldicarb, methomyl) cause transient inhibition of AChE enzyme.
    • Donepezil – used in Alzheimer’s therapy
  • Clinical Features: Sludge & Killer B’s (muscarinic effects)
    • Salivation
    • Lacrimation (crying-key feature)
    • Urination
    • Defecation (diarrhea)
    • GI cramping (distress)
    • Emesis
    • Bronchorrhea
    • Bronchospasm
    • Bradycardia
    • Pinpoint pupils (nicotinic)
    • Muscle weakness / fasciculations. (nicotinic)
    • Paralysis (nicotinic)
    • CNS depression / Coma / Seizure (nicotinic)
  • Treatment:
    • Decontamination
    • Supportive care: IV fluids, intubation (avoid succinylcholine because AChE metabolized)
    • Seizures- give benzodiazepines
    • Atropine – Binds muscarinic receptors, temporarily blocking them.
      • 2-5 mg IV, 0.05 mg/kg IV peds.
      • Double dose q3-5min until secretions and bronchospasm improving.
      • Infusion may be necessary depending on amount of exposure.
    • Pralidoxime (2PAM) – Reactivates AChE but has a transient inhibition effect on the enzyme so should be given in conjunction with atropine.
      • Bolus IV over 30 min- 30 mg/kg adult, 25-50 mg/kg peds
      • Infusion – 8 mg/kg/hr adult, 10-20 mg/kg/hr peds

Sympathomimetic 

  • Physiology: Sympathetic nervous stimulation by increasing circulating levels of cathecolamins (epinephrine, norepinephrine, and dopamine). This can be accomplished through multiple mechanisms: directly activating catecholamine receptors,  blocking breakdown, or blocking reuptake, or increasing release of catecholamines. These chemicals are neurotransmitters AND hormones.
  • Drugs:
    • Amphetamines
    • Bath Salts
    • Cocaine
    • Ecstasy (MDMA)
    • Ketamine
    • Synthetic Cannabinoids
  • Clinical Features:
    • Hyperthermia
    • Tachycardia
    • Hypertension
    • Agitation / Psychosis
    • Seizures
    • Dilated Pupils (but will react to light)
    • Diaphoresis, secondary to hyperthermia
  • Differential diagnoses not to forget:
    • Menningitis
    • Sepsis
    • Encephalitis
    • NMS
    • Serotonin Syndrome
    • Malignant Hyperthermia
    • Anticholinergic Toxicity
    • Heat Stroke
    • Pheochromocytoma
    • Thyroid Storm
    • Delirium Tremens
    • Rhambdomyolysis
  • Treatment:
    • Supportive care: IV fluids, cooling
    • Benzodiazepines for HTN, hyperthermia, and agitation
    • Nitroprusside or phentolamine for HTN.
    • Avoid succinylcholine as potential for hyper-K
    • Avoid antipyretics
    • Avoid pure beta-blockers

Opioid

  • Physiology: stimulation of three receptors provides CNS depression and analgesia: mu (MOP), kappa (KOP) and sigma (DOP)
  • Drugs:
    • Natural opiate derivatives: codeine, heroin, hydrocodone,, morphine, oxycodone
    • Synthetic: buprenorphone, dextromethorphan, fentanyl, methadone, meperidine
  • Clinical Features:
    • Bradypnea (key finding)
    • Bradycardia
    • Hypotension
    • CNS depression, coma
    • Pinpoint pupils
    • Seizures in mixed ingestion (tramadol)
    • QT prolongation (methadone)
    • Bowel obstruction
    • Non-cardiogenic pulmonary edema (heroin)
  • Differential diagnoses not to forget:
    • Hypoglycemia
    • Post-ictal
    • CVA (brainstem hemorrhage)
    • Clonidine overdose
    • Tylenol overdose (frequent co-ingestion)
  • Treatment
    • Supportive measures
    • Narcan 0.4-2mg IV q 3 min up to 10mg. Use lower doses if opiate dependent 0.05mg IV
    • Narcan Infusion 2/3 of the required dose to wake up patient, per hr, mixed in 1L D5W

Sedative-Hypnotic

  • Physiology: CNS depressants, typically by increasing GABA neurotransmission.
  • Drugs:
    • Barbiturates
    • Benzodiazepines
    • Chloral Hydrate
    • Gamma hydroxybutyrate (GHB)
    • Ethanol
    • Ethylene Glycol
    • Isopropyl Alcohol
    • Methanol
    • General anesthetics
    • Cannabanoids
    • Muscle relaxants
  • Clinical Features:
    • Hypothermia
    • Bradypnea
    • Bradycardia
    • Hypotension
    • CNS depressions / lethargy / coma
  • Differential diagnoses not to forget:
    • Co-ingestions common – opiates, tylenol
    • Alcohols ingested may not be ethanol
  • Treatment:
    • Supportive measures
Image source: Sketchymedicine.com, Author: ali@sketchymedicine.com

Basic Physiology:

The autonomic nervous system is divided in to the parasympathetic and sympathetic systems. The parasympathetic nervous system is responsible for functions such as digestion, urination, defacation, salivation, lacrimation, respiratory secretions, and sexual arousal. Acetylcholine is its chief neurotransmitter, found centrally and peripherally. It acts at nicotinic receptors (nerve to nerve, nerve to skeletal muscle) and muscarinic receptors (nerve to organ, nerve to smooth muscle). The sympathetic nervous system is responsible for the flight-or-flight response. Overstimulation is seen due to effects of chatecolamines.

References:

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