Synthetic cathinone toxicity

Background

Chemical structure of cathinone[1]
  • Cathinone is naturally occurring β-ketone analog of amphetamine found in the leaves of the “khat” plant (Catha edulis) consumed recreationally in Arabian peninsula and northeast Africa
  • Methcathinone first synthesized in 1928
  • Sharp increase in exposures around 2007-2011 due to products sold as “bath salts” and labelled “not for human consumption”
  • Common synthetic versions found today include mephedrone, methylone, MDPV, and many others
  • Bupropion is only cathinone derivative used medically in the US and Europe

Mechanism of Action

  • Thought to be similar to MOA of amphetamines and MDMA (increase of NE, dopamine and serotonin concentrations in synapses)
    • Inhibition of monoamine uptake transporters
    • Release of neurotransmitters from intracellular stores
  • Beta-ketone group decreases ability to penetrate BBB

Sympathomimetics

Clinical Features

Man chewing khat (Yemen).
  • Presents similar to other sympathomimetics
  • Patient experiences euphoria, increased energy, agitation, psychosis, hallucinations
  • Case reports suggest tachycardia tends to be more severe than hypertension (HR >150 and SBP<150)
  • Can lead to psychosis, agitated delirium, seizures, hyperthermia, rhabdo, cardiovascular collapse, renal failure, hepatic dysfunction, DIC and death
    • Retrospective review showed OR of 3.09 and 7.98 for rhabdomyolysis and severe rhabdomyolysis compared to other sympathomimetics

Differential Diagnosis

Differential Diagnosis

Toxidrome Chart

Finding Cholinergic Anticholinergic Sympathomimetic Sympatholytic^ Sedative/Hypnotic
Example Organophosphates TCAs Cocaine Clonidine ETOH
Temp Nl Nl / ↑ Nl / ↑ Nl / ↓ Nl / ↓
RR Variable Nl / ↓ Variable Nl / ↓ Nl / ↓
HR Variable ↑ (sig) Nl / ↓ Nl / ↓
BP Nl / ↓ Nl / ↓
LOC Nl / Lethargic Nl, agitated, psychotic, comatose Nl, agitated, psychotic Nl, Lethargic, or Comatose Nl, Lethargic, or Comatose
Pupils Variable Mydriatic Mydriatic Nl / Miotic
Motor Fasciculations, Flacid Paralysis  Nl Nl / Agitated Nl
Skin Sweating (sig) Hot, dry Sweating Dry
Lungs Bronchospasm / rhinorrhea Nl Nl Nl
Bowel Sounds Hyperactive (SLUDGE) ↓ / Absent Nl / ↓ Nl / ↓
^Consider Sympatholytic when looking at Sedative OD or someone who doesn't respond to Narcan
Withdrawal from substances have the opposite effect

Altered mental status and fever

Treatment

  • Consider GI decon with Activated Charcoal if patient presents <2 hours after ingestion and remains cooperative

Sedation

  • Decreases the risk of hyperthermia, rhabdo, traumatic injuries
  • Benzos are agents of choice especially increase seizure threshold[2]
    • Repeat boluses every 5-15 minutes as needed to halt seizures and provide adequate sedation
    • Goal: QRS duration < 110 msec

Cholinesterase inhibition

  • Indicated for severe agitation or delirium (esp if unresponsive to benzos)
  • Contraindicated in QRS>100 or Na blockade signs (R' in aVR) and in narrow angle glaucoma
  • Relatively contraindicated in asthma or ileus
  • Physostigmine - strongly consider poison control consult before giving
    • Crosses blood brain barrier, can be used to help make dx
    • Dosing: 0.5mg-1mg IV over 5min (repeat dosing up to 2mg in first hour)[3]
    • Onset of action: 5-10min
    • If partial response, repeat x3
    • If 3 or more administrations are needed over a 6-hour period, start IV infusion (bolus 1-2 mg followed by 1 mg/hour)
    • Stop infusion every 12 hours to determine resolution of the toxidrome
    • Side effects: bradycardia, dysrhythmias, cholinergic excess[4]
    • Always have atropine at the bedside for bradycardia or cholinergic excess</ref>[5]
    • Contraindicated in TCA toxicity (associated with cardiac arrest) and in the presence of bradycardia or AV block

Other therapies

  • Sodium bicarbonate for conduction abnormalities (QRS prolongation)
    • 2 mEq/kg bolus (typically 2-3 amps of bicarb)
    • Begin continuous NaCO3 infusion at 250mL/hr if bolus effective
    • Solution preparation = 1L D5W mixed with 3 ampules NaHCO3

Evaluation

Workup

  • EKG, CBC, CMP, PT/INR, CK, APAP, ASA, ethanol

Diagnosis

  • Urine drug screen does not detect synthetic cathinones; must use GCMS

Management

Disposition

  • If persistently altered, admission for observation
  • Otherwise if workup unremarkable and patient alert and oriented, discharge

References

  1. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8(1):33-42. doi:10.1007/s13181-011-0193-z
  2. Baumann MH, Partilla JS, Lehner KR. Psychoactive "bath salts": not so soothing. Eur J Pharmacol. 2013 Jan 5;698(1-3):1-5. doi: 10.1016/j.ejphar.2012.11.020. Epub 2012 Nov 23. PMID: 23178799; PMCID: PMC3537229.
  3. O’Connor AD, Padilla-Jones A, Gerkin RD, Levine M. Prevalence of rhabdomyolysis in sympathomimetic toxicity: a comparison of stimulants. J Med Toxicol 2015 Jun;11(2):195-200.
    1. National Center for Biotechnology Information. PubChem Compound Summary for CID 62258, Cathinone. https://pubchem.ncbi.nlm.nih.gov/compound/Cathinone. Accessed Nov. 26, 2020.
    2. Burns MJ, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000:35(4):374-381.
    3. Rosenbaum C and Bird SB. Timing and frequency for physostigmine redosing for antimuscarininc toxicity. J Med Toxicol. 2010;6:386-92.
    4. Pentel P and Peterson CD. Aystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980 Nov;9(11):588-90.
    5. Nguyen TT, et al. Adverse events from physostigmine: an observational study. Am J Emerg Med. 2018;36:141-2.