Kavitha Srinivasan, M.D., Steven Lippmann, M.D.
                                          
Alpha pyrrolidinopentiophenone (a-PVP) commonly known as “flakka” or “gravel” is fast emerging as a new and dangerous drug of abuse. Initially gaining prominence in Florida, it is now frequently abused throughout our country. It belongs to the class of synthetic cathinones, commonly marketed as bath salts, plant food, or insect repellant and to avoid scrutiny marketed with packaging labels warning “not for human consumption”. In 2014, a-PVP was classified as a Schedule I drug.

Flakka is a crystalline powder which can be inhaled directly or vaporized in e-cigarettes, consumed orally, or injected after being mixed into a solution. A potent dopamine and norepinephrine transporter inhibitor, it acts as a psychostimulant and is highly addictive.

After consumption, somatic manifestations in people can include tachycardia, hypertension, palpitations, chest pain, diaphoresis, mydriasis, acute renal failure, acidosis, and occasionally seizures. Psychiatrically, agitation, confusion, and/or hallucinations may be observed inducing an excitable delirium or psychosis. There is also the potential for aggressive combativeness resulting in injury to self and/or others. Acute intoxication might result in hyperthermia, rhabdomyolysis, and a hyponatremia which can lead to cerebral edema with possible ictal events and/or death. Injection of a-PVP can result in necrotizing fasciitis and a compartment syndrome.

The diagnosis is clinical and the drug is not detectable by routine toxicology screening. Specific diagnostic tests like liquid chromatography-mass spectrometry can confirm the diagnosis, but such assays are not always available nor are results reported back fast enough to be useful in management of an emergency case. A prominent feature of cathinone intoxication is its prolonged duration of action. Consider cathinone intoxication clinically in patients with a history of substance abuse presenting with agitated delirium, hypertension, tachycardia, mydriasis, hyperthermia, and/or seizures.
 
There is no known specific antidote. Supportive care is the primary management. Important measures include airway protection and close somatic and mental status monitoring. Control of agitation with individualized benzodiazepine dose titration and apply physical restraints as needed. Correct electrolyte disturbances and hydrate. Blood pressure control might require antihypertensive medication with vasodilating agents, while avoiding beta blocker drugs, due to the risk of unopposed alpha adrenergic stimulation. Antipsychotic medicines may have a limited role in treatment, but require cautious prescribing in patients who are then already seizure prone due to cathinone toxicity.

Counsel all users about the dangers of repeated exposure. In all cases, people using flakka should always be offered and encouraged to undergo chemical dependence intervention therapy. Abstinence is the goal of treatment. Hopefully over time, more experience and research will advance understanding of this new public health concern.

Suggested Readings:
1.    “Flakka” (alpha-PVP). (2015, April 06). Retrieved February 11, 2016, from http://www.drugabuse.gov/emerging-trends/flakka-alpha-pvp
2.    Rules 2014, Notice of Intent: Temporary Placement of 10 Synthetic Cathinones into Schedule I. (2014, January 28). Retrieved February 11, 2016, from http://www.deadiversion.usdoj.gov/fed_regs/rules/2014/fr0128.htm
3.    Marusich J, Antonazzo K, Wiley J, et al. Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3, 4-methylenedioxypyrovalerone (MDPV)Neuropharmacology. 2014; 87: 206–213
4.    Paillet-Loilier M, Cesbron A, Le Boisselier R, et al. Emerging drugs of abuse: Current perspectives on substituted cathinones Substance Abuse Rehabilitation. 2014; 5: 37–52