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Alpha-PVP (aka “Flakka” or “Gravel”) Introduction: -Also referred to as Alpha-pyrrolidinovalerophenone, alpha-pyrrolidinopentiophenone, (RS)-1-phenyl-2-(1-pyrrolidinyl)-1-pentanone -Cathinone is a natural stimulant found in the khat plant -Synthetic cathinones, aka “Bath salts”, refer to a collective group of compounds that are highly potent stimulants and are similar to MDMA, cocaine, and methamphetamine -The most common compound found in bath salts is MDPV (3,4-methylenedioxypyrovalerone) -Alpha-PVP is not a “second generation bath salt”; it was actually first synthesized in the 1960’s -Alpha-PVP has been recently been linked to multiple reported deaths in Florida -Alpha-PVP was added to the controlled substance list in the USA in 2014 Structure: -Alpha-PVP typically comes in a crystal form -Formula: C15H21NO
Pharmacology/Pharmacokinetics:
-Alpha-PVP’s mechanism of action is believed to involve inhibition of the reuptake of norepinephrine, dopamine, and serotonin -Rat studies have showed that alpha-PVP is both an uptake blocker of norephinephrine/dopamine and stimulates dopamine release Absorption/Distribution/Metabolism/Excretion: Absorption -Can be taken orally, sublingually, injected, vaporized, or intranasal -Onset of desired effects (euphoria) in 5-30 minutes and lasts for 1-3 hours. However, the undesired side effects (including psychosis) can last days Distribution -Postmortem studies have found alpha-PVP uniformly distributed among multiple tissues (blood, brain, muscle, CSF, lung, kidney, and liver) Metabolism -Six phase I metabolites have been identified -Lactam is the major metabolite Excretion -A study of postmortem alpha-PVP levels showed the highest concentrations were found in urine and the lowest concentrations were found in the liver → suggesting the drug is excreted chiefly by the renal system Significant Drug/Drug Interactions: -Co-ingestion of alcohol, other stimulants, and other illicit drugs has been shown to enhance the effects of the drugs -A large proportion of the fatal cases of alpha-PVP have involved co-ingestions of multiples drugs and alcohol Toxicity/Mechanism of Toxicity: -LD50 has not been determined -The potency and efficacy of alpha-PVP and MDPV are very similar in rat studies -Rat studies showed increased locomotor signs with doses ranging from 1mg/kg to 30mg/kg -A few case reports of drug-related fatalities with serum alpha-PVP levels have been reported: 0.1mg/L, 0.29mg/L, 0.52mg/L, 0.901mg/L -All serum levels determined by liquid-mass-mass spectrometry method -There is a significant overlap between concentrations tolerated by individuals and those reported in drug-related fatalities → alpha-PVP concentration alone does not determine toxicity Clinical Toxicity/Presentation: -Increased dopamine causes euphoria, increased activity, and hyperstimulation -Increased norepinephrine increases heart rate and blood pressure -Increased serotonin can cause hallucinations, delirium, and paranoia -Severe agitated delirium and aggressive behavior have been reported -Life threatening severe toxicity: Serotonin syndrome, hyperthermia, hypotension, rhabdomyolysis, acute renal failure, liver failure, cardiac dysrhythmias, seizures -Chronic exposure: May lead to physical and psychological dependence with withdrawal symptoms Laboratories/Where it is made: -Mainly manufactured in China and India and then shipped to America by legal delivery companies -Unknown if manufactured in America currently Treatment/Management: -Treatment is symptomatic and supportive -Benzodiazepines for sedation/delirium/seizures/tachycardia/hypertension -IVF’s for dehydration frequently indicated -GI decontamination is not recommended. Single dose of activated charcoal may be considered for possible co-ingestion, but usually not clinically indicated. Hemodialysis is not effective for elimination. -Labs: Obtain electrolytes, renal function, hepatic enzymes, and CPK level -Serum drug levels are NOT clinically useful and NOT readily available -Obtain EKG and continuous cardiac monitoring -Frequent temperature monitoring and institute cooling measures as warranted (Hyperthermia is an indicator of severe toxicity) -Dispo: Minimal observation of 6-8 hours. If patient has persistent CNS stimulation, persistent tachycardia, seizures, or dysrhythmias →then warrants admission -Poison center should be consulted By: Dr. Patrick Jackson References:
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