Toxidromes

"Toxic Syndromes"

Pulse, respiratory rate, and temperature were incorporated into the bedside chart “vital signs”

play an important role beyond assessing and monitoring the overall status of a patient
• provide valuable physiologic clues to the toxicologic etiology
• severity of an illness
• Valuable parameter to assess and monitor a patient’s response to treatment

needed for comparison at later time
• Treatment and mixed ingestions

• Opioid ingestion --> Naloxone given

• $\uparrow$drug metabolism
• No EKG changes $\rightarrow$ unless due to underlying abnormality
• i.e. Hyperkalemia; cocaine ingestion

• $\downarrow$ drug metabolism
• EKG changes $\rightarrow$ Osborn waves

Depressed or agitated (mental status)
Eyes $\rightarrow$ may be only findings; miosis (constricted), mydriasis (dilated)

• Sympathomimetic
• Opioid
• Cholinergic
• Anticholinergic
• Sedative/ hypnotic

• Serotonin Syndrome
• Neuroleptic Malignant Syndrome

Excessive SYMPATHETIC stimulation involving:
• Epinephrine, norepinephrine, dopamine
• Enhance release of excitatory catecholamines
• Serotonin and NE reuptake inhibitors (SNRI)
• Block presynaptic reuptake of catecholamines
• Lengthen activation of postsynaptic terminal

• CV: Tachycardia, arrhythmias, hypertension +/‐ ICH
• CNS: Confusion with agitation, seizures
• RENAL: rhabdomyolysis, renal failure can result
• Diaphoresis, dilated pupils
• Anticholinergic pupils are non- reactive

Supportive care
•Monitor airway, diagnose ICH, rhabdo
• IVF for insensible loses and volume repletion
• Benzos, benzos, benzos, benzos!!
• BP management, if severe

•Primarily bind to the mu, kappa or delta opioid receptor
•Opioid act as agonists to these receptors

• Sedation, coma, miosis, respiratory depression, CNS depression
• Peripheral vasodilation,
Orthostatic hypotension, Flushing (histamine), Bronchospasm, Pulmonary edema, Seizures (meperidine,propoxyphene), EKG changes (meperidine, propoxyphene)

• Competitive opioid ($\mu$ receptor) antagonist : naloxone
• 0.4mg IVP or 2mg intranasal
• Goal of return of spontaneous respirations sufficient to ventilate the patient appropriately
• May have to redose as opiates may act longer than antagonist
• There are other longer acting opioid antagonists such as nalmefene and naltrexone but these are not often used

• Different agents have different mechanisms
• Many interfere in the GABA system
• GABA-A receptor
• BZD are positive allosteric modulators

• CNS depression, lethargy, somnolence, decreased responsive to stimuli
• Pure BZD OD—”normal vital signs”, coma when BZD are the only drug ingested
• In combination with opioids or other drugs
• Respiratory depression
• Bradycardia, hypotension

• Supportive care
• Be wary of the benzo “antidote”: flumazenil
• Antagonist at the benzo receptor (GABA-A)
• RARELY INDICATED
• If seizures develop either because of benzo withdrawal, a coingestant or metabolic
derangements, have to use 2nd line agents, barbiturates, for seizure control

• By definition, these agent ANTAGONIZE the effects of endogenous Acetylcholine
• Ach receptors are either nicotinic or muscarinic
The “anti‐cholinergic” drugs just block the muscarinic receptors

CNS muscarinic blockade:
•Confusion, Agitation
•Myoclonus, Tremor
•Picking movements
•Abnormal speech
•Hallucinations
•Coma

Peripheral muscarinic effects:
•Mydriasis, Anhidrosis
•Tachycardia, Urinary retention
•Ileus

Supportive care
▪ IVF to replace insensible losses from agitation, hyperthermia
• Benzos to stop agitation

Physostigmine (controversial)
• Induces cholinergic effects
• Short acting
• May help with uncontrollable delirium
• Do not use if ingestion not known

• Block acetylcholinesterase from working
• End up with excess of acetylcholine in synapses
• Leads to excess stimulation of the muscarinic and nicotinic systems
• Parasympathetic response
• Rest and digest

Muscarinic
• D ‐ Diarrhea
• U ‐ Urination
• M ‐ Miosis
• BBB – Bradycardia,
• Bronchorrhea, Bronchospasm
• E ‐ Emesis
• L ‐ Lacrimation
• S ‐ Salivation

Nicotinic
• M‐ Mydriasis
• T ‐ Tachycardia
• W ‐ Weakness
• (t) H ‐ Hypertension

Antagonize Muscarinic Symptoms: Atropine
Stop aging of enzyme blockade
Pralidoxime (aka 2‐PAM)
Prevent and terminate seizures
• Diazepam
Supportive care