Synthetic cathinone toxicity
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Background
- 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
- Cocaine
- Amphetamines
- Synthetic cathinones (khat)
- Ketamine
- Ecstasy (MDMA)
- Synthetic cannabinoids
- Bath salts
Clinical Features
- 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
- Sympathomimetic toxicity
- Red, dry skin and absent bowel sounds favors anticholinergic toxicity
- Encephalitis
- Head trauma
- ETOH/sedative withdrawal
- Neuroleptic Malignant Syndrome (NMS)
- Acute psychotic disorder
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
- Infectious
- Sepsis
- Meningitis
- Encephalitis
- Cerebral malaria
- Brain abscess
- Other
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
- In general, care is supportive
- IVF for dehydration/rhabdo/AKI
- Benzodiazepines for agitation
Disposition
- If persistently altered, admission for observation
- Otherwise if workup unremarkable and patient alert and oriented, discharge
References
- 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
- 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.
- 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.
- ↑ National Center for Biotechnology Information. PubChem Compound Summary for CID 62258, Cathinone. https://pubchem.ncbi.nlm.nih.gov/compound/Cathinone. Accessed Nov. 26, 2020.
- ↑ Burns MJ, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000:35(4):374-381.
- ↑ Rosenbaum C and Bird SB. Timing and frequency for physostigmine redosing for antimuscarininc toxicity. J Med Toxicol. 2010;6:386-92.
- ↑ Pentel P and Peterson CD. Aystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980 Nov;9(11):588-90.
- ↑ Nguyen TT, et al. Adverse events from physostigmine: an observational study. Am J Emerg Med. 2018;36:141-2.