Day # 88: Toxidromes

We are continuing our current theme of emergency psychiatry. Today we will discuss toxidromes which will include an introduction and an overview of common toxidromes.

Today's Content Level: Beginner, Intermediate

INTRODUCTION

•A toxidrome is defined as a clinical syndrome associated with dangerous levels of drug acting on neurotransmitter systems. 1

•Common clinical scenarios include evaluation/treatment of overdose (intentional or accidental), iatrogenic drug toxicity, or included in the workup for altered mental status / delirium.

•As this curriculum is specifically designed for mental health practitioners, we will not go into as much detail as we do in other posts. We will not be the primary doctors treating toxidromes since these are medical emergencies that require treatment in the emergency department, medical floors, or intensive care units. However, it is still very important that we are able to know enough about these clinical syndromes so that we can appropriately recognize and escalate these cases when we see them in our clinics or psychiatric wards.

General principles

• If suspected toxicity, prioritize acute stabilization and escalate care (ED, rapid response, urgent medicine consult, etc.). Utilize resources to include poison control, medical toxicology consultation, and PubChem database.

• Obtain focused history: medications/toxins ingested (time of ingestion, amount, if they vomitted); intent of ingestion and prior ingestions/attempts; current list of medication/supplements; pre-existing organ vulnerabilities; list of current symptoms and progression of symptoms; any interventions that have been performed.

• Perform physical exam: focus on vital signs (elevated or depressed), level of arousal (agitated or drowsy), pupil size, nystagmus, wet or dry mucous membranes, peripheral pulses, heart rhythm, lungs (rate, depth, wheezing, crackles), bowel sounds, skin (temperature, color), muscular tone, reflexes, clonus, abnormal movements, and screen for hallucinations.

• Studies: common studies include EKG, finger stick glucose, CMP, CBC, lactate, coags, troponin, CPK, ABG or VBG, urine pregnancy, tox screen, drug levels, +/- imaging (CXR for aspiration/edema), CT head to rule out intracranial pathology).

• Next steps: again, the priority is acute stabilization and escalation of care. Treatment consists of supportive care which includes cardiorespiratory support and elimination if possible (ex: activated charcoal). Give the antidote if available (see below). Often dextrose, oxygen, naloxone, and thiamine are given in undifferentiated altered mental status due to low risk and life saving potential.

COMMON TOXIDROMES

Sympathomimetic

• Sympathomimetic drugs = compounds which act to stimulate the sympathetic nervous system. Also known as adrenergic drugs.

• Causes: stimulants which include cocaine, amphetamines (including bath salts, MDMA, ephedrine), hallucinogens (PCP, ketamine), beta-2 agonists, over the counter decongestants, caffeine, and some weight loss supplements (ex: yohimbine).

• Signs/Symptoms: symptoms are straightforward to remember as the sympathetic (fight or flight) nervous system is activated. Patients may be agitated, paranoid, or hallucinating. Increased risk for seizure or coma. Psychomotor agitation (tremor, hyperreflexia). Complications include cardiac (MI, arrhythmias) hypertensive emergency (with end-organ damage), vascular trauma (arterial dissection, and intracranial hemorrhage). Cocaine is associated with rhabdomyolysis.

• ↑activity/rigidity, ↑HR/BP, ↑Temp, ↑Pupil Size, ↑RR, ↑Bowel Sounds, ↑Sweat.

• Treatment: primarily supportive care including rapid control of blood pressure (remember to avoid beta blockers in cocaine intoxication), IV fluids, +/- external cooling. Benzodiazepines can be used for treatment of agitation and seizures (in refractory cases barbiturates, propofol, and dexmedetomidifine have been used).

Anticholinergic

• Anticholinergic drugs = compounds that block the action of acetylcholine.

• Causes: "pure" anticholinergics include scopolamine, benztropine, trihexyphenidyl, oxybutynin, and plant-based (Jimson weed, angel's trumpet). A number of other medications have anticholinergic properties including antihistamines, atypical and low-potency antipsychotics, tricyclic antidepressants (TCAs), and cyclobenzaprine.

• Signs/Symptoms: symptoms can be remembered by the popular mnemonic -> “blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.” This refers to pupillary dilation and impaired lens accommodation, agitated delirium (can include hallucinations, stereotypic picking behaviors, dysarthric mumbling), flushing, hyperthermia, dry mucosa and skin, gastrointestinal and bladder paralysis, and tachycardia/hypertension. 2 Keep in mind that mixed toxidromes are common if due to antihistamines, antipsychotics, or TCAs.

• ↑activity/rigidity, ↑HR/BP, ↑Temp, ↑Pupil Size, ~ RR, ↓Bowel Sounds, ↓Sweat.

• Treatment: supportive care including activated charcoal (within 1-2 hours of ingestion), IV fluids, and external cooling. Benzodiazepines can be used for treatment of agitation and seizures. Physostigmine (reversible cholinesterase inhibitor) can be given in severe cases with expert guidance.

Cholinergic

• Cholinergic drugs = compounds that mimic/enhance the action of acetylcholine.

• Causes: examples include organophosphate and carbamate pesticides in accidental exposures or suicide attempts, and overdose on anti-cholinesterase inhibitors (ex: donepezil, rivastigmine, galantamine), muscarinic agonists (ex: muscarine, pilocarpine), or nicotinic agonists (ex: nicotine, varenicline).

• Signs/Symptoms: symptoms can be remembered by the popular mnemonic-> DUMBELLS (Diarrhea/diaphoresis; Urinary frequency; Miosis; Bronchospasm; Emesis; Lethargy; Lacrimation; Salivation). You can also simply conceptualize it as the opposite of anticholinergic toxicity described above. Nicotinic side effects can also lead to cramping, fasciculations, and can precipitate arrhythmias, seizures, and respiratory failure. Complications include life-threatening arrhythmias, respiratory compromise, electrolyte imbalances (GI losses), and delayed-onset polyneuropathy.

• ↓activity/rigidity, ↑↓HR/BP, ~Temp, ↓Pupil Size, ↑↓RR, ↑Bowel Sounds, ↑Sweat.

• Treatment: supportive care includes IV fluids (volume resuscitation), cardiorespiratory support, and decontamination in cases of pesticide exposure. Benzodiazepines can be used for treatment of agitation and seizures. Atropine (inhibits muscarinic acetylcholine receptors) and pralidoxime can also be given.

Serotonin Syndrome

• Discussed in detail on day # 33

• ↑activity/rigidity, ↑HR/BP, ↑Temp, ↑Pupil Size, ↑RR, ↑Bowel Sounds, ↑Sweat.

Neuroleptic Malignant Syndrome

• Discussed in detail on day # 14

• ↑activity/rigidity, ↑HR/BP, ↑Temp, ~Pupil Size, ↑RR, ~Bowel Sounds, ↑Sweat.

Opioid

• Opioid = any chemical (natural, synthetic, or semi-synthetic) that interacts with opioid receptors (mu, delta, kappa). Involved in pain and sedation.

• Causes: some opioids are legally prescribed for the treatment of pain (ex: oxycodone, hydrocodone, morphine, fentanyl, tramadol, methadone), but also includes the illegal drug heroin.

• Signs/Symptoms: opioids slow everything down, so you see drowsiness and attentional impairment, respiratory depression with shallow/slow breathing, decreased autonomics (bradycardia, hypotension, hypothermia), small constricted pupils, nausea/vomiting, constipation, and slurred speech. Complications include seizures, rhabdomyolysis, compartment syndrome (immobility), pulmonary edema, and hypoxic encephalopathy. Opioid intoxication can progress to coma and death. Keep in mind some opioids (tramadol, meperidine) can produced mixed serotonergic toxidrome.

• ↓activity/rigidity, ↓HR/BP, ↓Temp, ↓Pupil Size, ↓RR, ↓Bowel Sounds, ↓Sweat.

• Treatment: includes administration of naloxone (opioid antagonist) and supportive airway management and blood pressure support. Naloxone may require repeated or continuous dosing to restore RR to lower end of normal and maintain stability.

Sedative-Hypnotic

• Sedative-hypnotic = class of drugs that cause a dose-dependent depression of CNS function. They are used as sedatives, anxiolytics, muscle relaxants, anesthetics, and anticonvulsants.

• Causes: alcohol, benzodiazepines (BDZ), nonbenzodiazepines (Z drugs), barbiturates, muscle relaxants (ex: cyclobenzaprine, baclofen, methocarbamol), and gamma-hydroxybutyrate.

• Signs/Symptoms: many similarities to opioid intoxication including drowsiness, slurred speech, respiratory depression (more typically of barbiturate or BDZ + alcohol). Other symptoms include ataxia, nystagmus (often normal pupil size), hyporeflexia, and hypotonia. Can progress to coma and persistent delirium can occur. Co-ingestion of multiple sedatives can lead to life-threatening respiratory depression.

• ↓activity/rigidity, ↓HR/BP, ↓Temp, ~Pupil Size, ↓RR, ↓Bowel Sounds, ↓Sweat.

• Treatment: supportive care includes cardiorespiratory support, prevention of aspiration, and monitor for withdrawal. Flumazenil (benzodiazepine antagonist) can be given in severe cases with expert guidance, however it can precipitate seizure or arrhythmia in co-ingestions or in patients with epilepsy. Flumazenil is ineffective for barbiturate toxicity.

CONCLUSION

Nice work. In our next post we will have a review quiz which will cover topics in emergency psychiatry. After that we will be finished with this theme and move on to discuss OCD and other impulse control disorders.

Resources for today's post include Pocket Psychiatry and the articles referenced in the post.

Bullet Psych is an Amazon Associate and we receive a small commission if you use our links.