4.1 Types of Toxidromes

Fast and furious toxidromes

sympathomimetic and anticholinergic

Toxidrome downers

sedative-hypnotic and opioids

Sympathomimetic Toxidrome Vital Signs

Increased BP, Pulse, RR, Temp

Dilated pupils, wet skin

none to increased peristalsis

tremors, seizures, diaphoresis

Anticholinergic Toxidrome Vital Signs

Increased pulse, temp

variable BP and RR

dilated pupils, dry skin, decreased peristalsis

dry mucous, flush, urinary retention

Cholinergic Toxidrome Vital Signs

no change in RR, Temp

variable BP, Pulse

small pupils, wet skin, increased peristalsis

salivation, lacrimation, urination, diarrhea, bronchorrhea, faaciculations, paralysis

Opiate Toxidrome Vital Signs

Decreased BP, Pulse, RR, Temp

small pupils, decreased peristalsis, no chnage in skin

hypoflexia

Sedative/Hypnotic Toxidrome Vital Signs

Decreased BP, Pulse, RR, Temp

variable pupils. wet skin, decreased peristalsis

hypoflexia, ataxia

Withdrawal Vital Signs

Increased BP, Pulse

no change or increased RR, Temp

dilated pupils, wet skin, increased peristalsis

tremors, seizures, diaphoresis

Skin Characteristics of Different Toxidromes (Diaphoretic vs Dry)

Diaphoretic: sympathomimetics, serotonin toxcity, ethanol and sedative hypnotic withdrawal

Dry: antichlingeric toxicity

Eye Characteristics of Toxidromes (Mydratic, response, nystagmus)

Sympathomimetics: mydratic and briskly reponsive to light

Anticholinergics: mydriatic and poorly repsonsibe to light

Phencyclidine & Ketamine: vertical and rotatory nystagmus

Bowel Sound Characteristcs of Toxidromes

Active: sympathomimetics, serotonin toxcity, ethanol and sedative hypnotic withdrawal

Quiet or absent: anticholingeric

Bladder Characteristics of Toxidromes

Urinary Retention: anticholinergics, ketamine, phenycyclidine

Increased Urination: cholingergic

What toxidrome has spontaneous and inducible clonus that is more prounounced in the legs than in the arms?

serotonin toxicity

Causes of Sympathomimetic Toxidrome

• Upregulation and activation of the sympathetic system (direct or indirect effect on catecholamines; alpha and beta-adrenergic receptors)

• Exaggerated physiological response (fight or flight response)

Signs/Symptoms of Sympathomimetic Toxidrome

• Vitals: Tachycardia, hypertensive, hyperventilation, hyperthermia

• Mental Status: Agitated, Aggressive, Alert/Orientated

• Eyes: Mydriasis

• GI: Increased bowel sounds

• Urinary: Normal

• Skin: Diaphoretic (sweating)

• Mucus membranes: Normal

• Neuro: Increased muscular activity, CNS excitation, seizures, tremor

Common Agents that can cause Symapthomimetic Toxidrome

Amphetamines, cocaine, PCP, MAO-inhibitors, pseudoephedrine, phenylephrine, withdrawal from sedatives can trigger response

serotonin and norepinephrine reuptake inhibitors (SNRI) (mixed, serotonin syndrome presents simiarly to sympathomimetic)

Treatment/Antidote for Sympathomimetic Toxidrome

• Control agitation, potential seizures (Benzodiazepines)

• Control temperature (cooling)

• Anti-hypertensive

Causes of Anticholinergic Toxidrome

• Block parasympathetic system will result in unopposed sympathetic tone

• “Antimuscarinic” — excessive blockade of ACh at the muscarinic receptors

Signs/Symptoms of Anticholinergic Toxidrome

• Vitals: Tachycardia, hypertensive (mild), hyperthermia (mild), widen QRS

• Mental Status: Disoriented, delirium, hallucinations

• Eyes: Mydriasis

• GI: No bowel sounds, constipation

• Urinary: Retention

• Skin: Dry, flushed

• Mucus membranes: Dry

• Neuro: Mild increase muscular activity, seizures, garbled speech

Anticholinergic Toxidrome Mneumonic

• ‘Hot as hell’ — High temperature

• ‘Blind as a bat’ - Mydriasis

• ‘Dry as a bone’ - Dry skin, no secretions, cannot urinate (huge bladder)

• ‘Red as beat’ — Flushed skin

• ‘Mad as a hatter” — Confusion, agitation, delirium, seizures

Common Agents that cause Anticholinergic Toxidrome

• Blockade of ACh at muscarinic receptors — peripheral and central (salivary glands, GI tract, sweat glands, eyes)

• Multiple drugs and toxins found in nature: Atropine, antiemetics, scopolamine, antihistamines (ie., diphenhydramine, chlorpheniramine) , herbal supplements, antipsychotics, TCA’s

Treatment.Antidote for Anticholinergic Toxidrome

• Control delirium/agitation (Foley catheter, Benzodiazepines)

• Physostigmine — reversible acetylcholinesterase inhibitor (not always)

Adverse Effects of Physostigmine

Cholinergic Toxicity (Consult Medical Toxicologist)

• Bradycardia, Bronchospasm, Seizures

• Short duration of action

• Special access drug

Causes of Cholinergic Toxidrome

• Results from excessive levels of acetylcholine

• Inhibit acetylcholinesterases — increase acetylcholine

• Both central and peripheral nicotinic and muscarinic receptors (rest and digest response)

Signs/Symptoms of Cholinergic Toxidrome

Vary based on balance of nicotinic and muscarinic effects

• Vitals: Bradycardia, normal to low BP, hypothermia (mild), bronchospasm

• Mental Status: Agitation, confusion

• Eyes: Mitotic (miosis)

• GI: Diarrhea

• Urinary: Urination

• Skin: Profusely diaphoretic

• Mucus membranes: Copious excretions (bronchorrhea)

Nicotinic Receptor Mnemonic

Days of the Week

• Mydriasis

• Tachycardia

• Weakness

• tHypertension

• Fasciculations

• Seizures

Common Agents that cause Cholinergic Toxidrome

Organophosphates, insecticides, some mushrooms, chemical warfare agents (sarin nerve gas), nicotine, physostigmine, pilocarpine

SLUDGE + Killer B's Mnemonic for Cholinergic Toxidrome

Salivation, Lacrimation, Urination, Diarrhea, Gl upset, Emesis (Sludge)

Bradycardia, bronchospasm, bronchorrhea (Atropine — a lot)

DUMBELS Mnemonic for Cholinergic Toxidrome

Diarrhea, Urination, Miosis, Bronchospasm, Emesis, Lacrimation, Salivation

Treatment/Antidote for Cholinergic Toxidrome

Atropine — muscarinic receptors

Pralidoxime (2-PAM) — nicotinic receptors

Causes of Sedative/Hypnotic Toxidrome

CNS depression leading to a decreased consciousness, modulate activity of GABA neurotransmitter complex

Increased frequency Cl- channel opening → Hyperpolarization → Inhibit AP → VSMC, medulla oblongata, CNS, thalamus, hypothalamus, limbic system - Vasodilation, decrease cerebral blood flow, decrease respiration, amnesia, decrease anxiety

Signs/Symptoms of Sedative/Hypnotic Toxidrome

• Vitals: Decrease HR, Decreased BP, hypothermia, loss of airway protective reflexes, respiratory rate depression

• Mental Status: Sleepy, somnolence, sedation

• Eyes: No change

• Gl: No bowel sounds

• Urinary: Retention

• Skin: Dry, flushed

• Mucus membranes: Dry

• Neuro: Some ataxia, hypoflexia

Common agents that cause Sedative/Hypnotic Toxidrome

Benzodiazepines, barbiturates, ethanol, chloral hydrate

Treament/Antidote for Sedative/Hypnotic Toxidrome

Flumazenil but caution/risky — chronic users so trigger withdrawal and often co-ingestion (antipsychotics, TCA, EtOH) increases the risk of seizures or cardiac arrhythmias

Causes of Opioid Toxidrome

• Binding to opiate receptors (mu, Kappa, delta)

• Organs primarily affected — CNS, ocular, GI and respiratory

Signs/Symptoms of Opioid Toxidrome

• Vitals: Bradycardia, respiratory depression, hypotension, decreased pulse, hypothermia

• Mental Status: Drowsiness, loss of consciousness, coma

• Eyes: Mitotic/small

• Gl: Decreased motility

• Skin: Normal, blue lips or nails

Common Drugs causing Opioid Toxidrome

opioids — codeine, morphine, heroin, hydrocodone, fentanyl

Opioid Treament

naloxone

Causes of SEROTONERGIC TOXIDROME (Serotonin Toxicity)

• Results from excess serotonin activity in CNS

• Mainly involved 5-HT,, and 5-HT>», (central and peripheral) (i) Cognitive, (ii) autonomic and (iii) neuromuscular effects

• Effect thermoregulation, behavior and regulation of neuronal networks in brain and spinal cord

General Mechanisms of Serotonergic Toxidrome

• Enhanced 5-HT synthesis

• Prevent vesicle uptake of 5-HT

• Increase cytoplasmic concentrations of 5-HT

• Displace 5-HT from vesicles or inhibit MAO

• Activate or antagonize 5-HT receptors

• Inhibit 5-HT reuptake

Mental Status Changes of Serotonergic Toxidrome

Agitation, confusion, delirium, anxiety Severe cases: Seizures or coma

Autonomic dysfunction of Serotonergic Toxidrome

Hyperthermia, tachycardia, hypertension Sweating, diarrhea Dilated pupils (mydriasis)

Neuromuscular hyperactivity of Serotonergic Toxidrome

Tremors, myoclonus (involuntary muscle jerks), Hyperreflexia, especially in the lower limbs, Clonus (spontaneous, inducible, or ocular), Muscle rigidity

Signs/Symptoms of Serotonergic Toxidrome

• Vitals: Tachycardia, hyperthermia, hypertension

• Mental Status: Agitation, anxiety, confusion, seizures

• Eyes: Mydriasis

• GI: Increased bowel sounds

• Skin: Diaphoresis

• Neuromusc: muscle rigidity, hyperreflexia, tremors, shivering, myoclonus

Common drugs/toxicants causing Serotonergic Toxidrome

• Many drugs, often associated with psychiatric medications.

• Antidepressants (SSRIs , SNRIs, TCAs, MAOIs )

• Lithium, Tramadol, MDMA

Treatment/Antidote for Serotonergic Toxidrome

• Cyproheptadine (1st generation histamine-1 blocker with non-specific serotonin (5HT) antagonism

• Discontinue offending medications, supportive care, intubation/ventilation, benzodiazepines

Alcohol Withdrawal Characteristics

develop ~6-24hr after last drink

• Autonomic excitation (tremors, agitation, sweating, THR, TBP, ttemp)

• Neuro-excitation (hyperflexia, nightmares, hallucinations, generalized seizures)

• Delirium tremens (DTs) (severe form lethal, altered mental state, sympathetic overdrive)

Sedative-hypnotic withdrawal Characteristics

develop ~2-10d after abruptly stopping

• Similar to EtOH withdrawal

• Agitation, insomnia, inattention, palpitations, hallucinations, spasticity, photophobia

Opioid withdrawal Characteristics

depends upon on drug, ie., onset <6h heroin or >2days methadone

• Not usually life-threatening

• Anxiety, restlessness, insomnia, craving, lacrimation, rhinorrhea, salivation, anorexia, abdominal cramps, diarrhea, mydriasis, piloerection, flushing, joint/muscle aches, THR, TBP

Drug Induced Hyperthermia Causes

• Serotonin syndrome

• Neuroleptic malignant syndrome

• Sympathomimetics

• Anticholinergics

• Heat production overcomes heat dissipation/loss

• Core temperature reaches 40 - 40.5°C

Outcomes of Untreated Drug Induced Hyperthermia

• May lead to cerebral edema, myocardial dysfunction, disseminated intravascular coagulopathy

• Increased intestinal permeability (ie., to endotoxins - sepsis)

Management of Drug Induced Hyperthermia

• ABCs

• Accurate core temperature measure

• Sedation

• Active cooling (<39°C within 20-30min) ice water bath