flakka

1. FLAKKA
By: Hind Talib
Supervised by : Dr. Ammar
Ali

2. INTRODUCTION
 Alpha-pyrrolidinovalerophenone (α-PVP) is a sympathomimetic drug .
 It was developed by Boehringer Ingelheim as a central nervous system
stimulant and pressor agent in the1960.
 It can be easily manufactured and purchased through the Internet or in
retail shops and is usually sold as ‘‘bath salts’’. Flakka is Second
Generation Bath Salts.
 It is popular among youth and homeless , now it mixed in batches of
cocaine, molly, heroin, crystal meth, etc .
 Flakka is a very addictive substance created in laboratories in order to
produce euphoric symptoms in people trying to obtain a cheap, quick high.

4. PREVALENCE AND USE
• Alpha -PVP is considered as a popular recreational drug in Japan(12)
and it is also abused in Denmark, Finland, Iceland, Norway and
Sweden, as well as in the USA and Australia.
• the packages of the commercial products have the indication ‘‘not for
human consumption’’ or ‘‘for research use only’’ .

5. ROUTES OF ADMINISTRATION

6. SYNTHESIS OF ALPHA -PVP
i. α-halogenation (e.g. using bromine) of the 1-phenylpentan-1-one (valerophenone)
precursor (a) and formation of the 2-bromo-1-phenylpentan-1-one (b).
ii. Reaction with pyrrolidine gives α-PVP (c) that can then be converted into a range of
salts.

7. PHARMACOLOGY
• Alpha-PVP increases the release of dopamine from dopaminergic
neurons within the mesolimbic cortex via dopamine transporters and
also inhibits its reuptake.
• It is also inhibits the reuptake of norepinephrine and, to a lesser extent,
serotonin.
• The drug produced robust and long-lasting (240–290 min) stimulation of
locomotor activity.

8. DESIRED EFFECT FROM FLAKKA
ABUSE
• euphoria, alertness, talkativeness, sexual arousal, focused mind, and an
overall positive feeling.
• body temperature has been observed to decrease.

9. TOXICITY
• Flakka is highly addictive, both physically and psychologically.

10. ALPHA –PVP METABOLISM
• Hydroxylation of the side chain followed by dehydrogenation to the
corresponding ketone.
• Hydroxylation of the 2-position of the pyrrolidine ring followed by
dehydrogenation to the corresponding lactam.
• Degradation of the pyrrolidine ring to the corresponding primary amine.
• Hydroxylation of the phenyl ring, most probably in the4-position.
• Ring opening of the pyrrolidine ring to the corresponding carboxylic acid.

12. INTOXICATIONS AND FATALITIES
• Alpha -PVP has been detected in six fatal cases reported in Ohio. The
decedents were four females and two males. In the first four cases,
Blood and urine samples were found positive for alpha -PVP analyzed
by GC–MS and LC–MS after proper sample pretreatments. The
presence of other drugs of abuse was also confirmed.

13. FLAKKA TRIGGERING BIZARRE
BEHAVIOR
• Because of “Excessive dopaminergic activity it can produce acute
choreoathetosis and acute Gilles de la Tourette syndrome.
• Because alpha -PVP also blocks the re-uptake of norepinephrine, it
produces sympathomimetic manifestations .

14. TREATMENT
• Supportive care, no antidote available .
• Significant hyperthermia may require passive or active cooling.
• Safely sedating and calming agitated patient :
• -Higher dose IV lorazepam (2mg) or Diazepam (10mg) .
• -Ketamine when benzodiazepines fail .
• mechanical ventilation
• Aggressive IV fluid repletion (Normal Saline) at least 1-2 Liters.
• Dialysis commonly employed for severe rhabdomyolysis cases that fail
to improve with IV fluid.