Objectives. True/False 12/22/2015. Flakka Abuse: An Emerging Domestic Threat. Flakka use will trigger a positive result on a toxicology screen

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1 Flakka Abuse: An Emerging Domestic Threat Ravin Seewah, Pharm.D. PGY-I Pharmacy Resident Broward Health Medical Center Objectives Differentiate between Flakka intoxication and other drugs that present with a similar toxidrome Discuss the effects of elevated neurotransmitters List the potential complications associated with the use of Flakka Understand the role in therapy for medications used to manage Flakka intoxication Identify monitoring parameters when managing patients with Flakka intoxication True/False Flakka use will trigger a positive result on a toxicology screen 1

2 True/False Flakka is inexpensive compared to other drugs and is one reason why its abuse has skyrocketed True/False Flakka can only be smoked In the Media Police arrested a Fort Lauderdale man high on Flakka earlier this month after he allegedly ran down a major street wearing only sneakers. The man, 35, told officers he was being pursued by people who had stolen his clothes, and was trying to get hit by a car so they would stop chasing him. Broward Boulevard Streaker High on Flakka [Video file]. (2015, April 6). Retrieved from broward-boulevard-flakka-streaker story.html 2

3 In the Media In a separate incident in early April, Fort Lauderdale officers arrested a man trying to kick in the door at police headquarters, exhibiting nearly superhuman strength. This man believed several cars were chasing him and ran to the police department for help. When he couldn t break the door down, he began attacking the building s hurricane-resistant glass with big rocks. Man Fueled By Flakka Tries To Kick In Door At Police Headquarters. (2015, March 11). Retrieved from Flakka Flakka, also known as Gravel, is the latest version of bath salts containing a dangerous synthetic chemical compound identified as Alpha-PVP Alpha-pyrrolidinopentiophenone Class Synthetic Cathinone Name Origination The name Flakka comes from the Hispanic word that translates into a beautiful, elegant woman who charms all she meets The word flaca in Spanish also translates to skinny woman Prosser J, Nelson L. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8:

4 Cathinones Cathinones are chemicals derived from the Khat plant (Catha Edulis) grown in the Middle East and Somalia, where the leaves are frequently chewed for their stimulant effects. Prosser J, Nelson L. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8: Synthetic Cathinones Synthetic cathinones are related to the parent compound cathinone Cathinone is chemically similar to ephedrine, cathine, methcathinone, and other amphetamines Synthetic cathinones are stronger versions of the compound found in fresh Khat. Alpha-PVP is a compound that structurally resembles MDPV (methylenedioxypyrovalerone), a psychoactive stimulant often abused for recreational purposes. MDPV is a norepinephrine-dopamine reuptake inhibitor. MDPV was developed in the 1960s but gained popularity around 2004 on the streets as a designer drug. Prosser J, Nelson L. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8: Mechanism of Action Alpha-PVP contains a pyrrolidine ring, a 5- sided nitrogen containing component that enables the molecule to effectively block the reuptake of dopamine, norepinephrine and serotonin transporter. Prosser J, Nelson L. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8:

5 Structure Relation Amphetamine Cathinone Methamphetamine Alpha-PVP Prosser J, Nelson L. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8: Effects of Elevated Dopamine Benefits: Enhanced concentration Increased energy Mood elevation Engagement in risky behaviors Hallucinations Insomnia Adverse Effects: Anxiety Agitation Paranoia Hyperactivity Movement disorders Loss of self control Hallucinations Seizures Gregg RA, Rawls SM. Behavioral pharmacology of designer cathinones: a review of the preclinical literature. Life sciences. 2014;97(1): Effects of Elevated Norepinephrine Benefits: Increased attention Increased concentration Adverse Effects: Hypertension Tachycardia Palpitations Diaphoresis GI disturbances Anxiety Gregg RA, Rawls SM. Behavioral pharmacology of designer cathinones: a review of the preclinical literature. Life sciences. 2014;97(1):

6 Effects of Elevated Serotonin Benefits: Increased release of oxytocin and vasopressin Elevated empathy Sexual arousal Adverse Effects: Thermal dysregulation GI disturbances Seizures Loss of muscle coordination Muscle rigidity Gregg RA, Rawls SM. Behavioral pharmacology of designer cathinones: a review of the preclinical literature. Life sciences. 2014;97(1): Appearance Flakka is a crystalline substance resembling rock candy It takes the form of a white or pink, foulsmelling crystal Administration Injected Poured into capsules and ingested Smoked in an e-cigarette or joint 6

7 Detection Alpha-PVP may be quantified in blood, plasma or urine by liquid chromatographymass spectrometry to confirm a diagnosis of poisoning Blood or plasma alpha-pvp concentrations are expected to be in a range of: ug/l: in persons using the drug recreationally > 100 ug/l: in intoxicated patients > 300 ug/l: in victims of acute overdose,, ProMarusich J.A., Antonazzo K.R., Baumann M.H., et al. Pharmacology of novel synthetic stimulants structurally related to the bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology. 2014;87: Excited Delirium Medical Emergency! Someone experiencing excited delirium often exhibit signs of: Bizarre and/or aggressive behavior Severe hallucinations Extreme paranoia Disorientation and panicking Speech disturbances Insensitivity to pain Superhuman strength Elevated body temperature Diaphoresis M. Vilke, M. DeBard, C. Hall, et al. Excited delirium syndrome (ExDS): defining based on a review of the literature. J Emerg Med. 2012;43(5):

8 Rhabdomyolysis Complications This can lead to kidney failure and result in a user needing dialysis Hyperthermia QTc Prolongation Arrhythmias Seizures Death M. Vilke, M. DeBard, C. Hall, et al. Excited delirium syndrome (ExDS): defining based on a review of the literature. J Emerg Med. 2012;43(5): ER Management Prepare an appropriate team to receive the patient Ensure a safe environment Avoid unnecessary stimulation (bright lights, loud noise, crowds) Physically restraining patients should be AVOIDED Observe & monitor patient vigilantly Consult psychiatry Admit if necessary Physical exam Labs Work-Up CBC, CMP, CK levels Urine Drug Screen EKG Troponin (if MI is suspected) 8

9 General Approach Management Manage psychomotor agitation Benzodiazepines, Antipsychotics, Sedatives Airway management May need to intubate patient Seizure prophylaxis Benzodiazepines Fluid resuscitation Manage hypertension Generally controlled with the benzodiazepines used for agitation Manage hyperthermia Management A combination of physical control and chemical sedation are often necessary initially to manage severely agitated patients Treatment of Agitation and Adrenergic Symptoms Benzodiazepine + Sedative Treatment of Agitation and Psychosis Antipsychotic + Benzodiazepine + Sedative Treatment Benzodiazepines Avoid long-acting benzodiazepines Recommend Lorazepam (Ativan) 2 mg IM/IV every 60 minutes as needed for agitation Max dose: 10 mg daily Less offensive to the liver Diazepam (Valium) 5-10 mg IM every 60 minutes as needed for agitation Max dose: 60 mg daily Sedatives Recommend Diphenhydramine (Benadryl) mg IM/IV every 4 hours as needed Max dose: 400 mg daily 9

10 Antipsychotics Avoid Treatment Haloperidol (Haldol): Lowers seizure threshold, increases risk of dystonias, EPS, may increase CK Ziprasidone (Geodon): May prolong the QTc interval Recommend Olanzapine (Zyprexa) 10 mg IM one time for agitation and psychosis May repeat 10 mg IM one time after 2 hours May repeat 10 mg IM once after 6 hours (6 hours from initial dose, 4 hours from dose 2) Max dose: 30 mg daily Chlorpromazine (Thorazine) 25 mg IM May repeat dose in 1-4 hours Max dose: 400 mg every 4-6 hr Emergency Care: The Big Four Zyprexa (Olanzapine) Atypical antipsychotic Approved for the treatment of schizophrenia and bipolar disorder Choose One Chlorpromazine (Thorazine) 1 st generation antipsychotic Approved for the treatment of schizophrenia and bipolar disorder Ativan (Lorazepam) Benzodiazepine Short-acting central nervous system depressant Used for sedation and agitation Benadryl (Diphenhydramine) Antihistamine Used for sedation Zyprexa [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015 Thorazine [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2013 Benadryl [package insert]. Franklin Lakes, NJ: BD Rx Inc; 2015 Ativan [package insert]. Bridgewater, NJ: Biovail Pharmaceuticals Inc; 2015 Hyperthermia When the body temperatures are above 104 F, it is considered life-threatening At 106 F, brain death begins At 113 F, death is nearly certain Aggressively cool the patient with ice packs and cold normal saline IVs 10

11 Supportive Care Fluid Resuscitation Hypovolemia is frequently associated with agitated delirium IV isotonic crystalloids should be given to patients with signs of volume depletion NaCl 0.9% ml/kg IV Monitor Renal function Fluid input and output Maintain a urine output of at least 3 ml/kg/hr Monitoring Electrocardiogram (EKG) Vital Signs -Hypotension -Respiratory depression -Hyperthermia Mental Status -CNS depression Disposition Transition to oral therapy should be made when patient is cooperative Patients should be observed until they are no longer symptomatic and rhabdomyolysis has been ruled out Refer patients to outpatient detoxification centers Hospital admission is needed for patients with persistent psychosis or other concerning clinical findings Signs of cardiac ischemia Unstable vital signs Actively seizing 11

12 Patient Case A 35 year old Caucasian male is brought in to the Broward Health Medical Center Emergency Department by Emergency Medical Services after being found rolling on the ground in downtown Ft. Lauderdale with what appears to be an acutely psychotic state. He is shirtless, covered in dirt and presents agitated, thrashing violently and screaming threats at the medical staff. He has been physically restrained to the bed and continues to struggle against restraints. His vital signs are T F, HR 125, RR 25, BP 130/84, O 2 sat 94% on room air. His pupils are dilated, his skin is warm and he is diaphoretic. The patient insists that he be let go, remaining preoccupied with the FBI trying to apprehend him. Urine toxicology screen, EKG, electrolytes and comprehensive metabolic panel have been ordered. What is the next best step in management? A. Administer haloperidol as the psychotic patient is at risk to harm himself and others B. Administer benzodiazepines to decrease his risk for sudden death or seizures C. Allow the patient to sign out AMA D. Administer beta blockers as his heart rate is elevated and may be having an arrhythmia or MI E. Administer bicarbonate to decrease his risk for long QT interval Public Concerns Flakka is one of a number of cathinone-based drugs that are produced in China and sold online to small-time drug gangs in the U.S. A single dose of Flakka is about a tenth of one gram and costs just $4-5. The main issue with this whole category is that the user just does not know what they re taking or the strength of what they re taking. The U.S. National Institute on Drug Abuse has warned that smoking Flakka can send the drug very quickly into the bloodstream, making it particularly easy to overdose. Domestic Threat According to Broward County Sheriff s office, Alpha-PVP use jumped from 0 to 190 cases in In the first three months of 2015, police have already seen 275 cases. The numbers pushed synthetic drug reports in Broward County to account for 34% of all narcotic cases, surpassing cocaine for the first time in two decades. 12

13 Legal Status Schedule I drug in the United States As of October 2015, Alpha-PVP is a controlled substance in China 13

14 Questions 14