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Arbi Nazarian, Ph'D'

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Arbi Nazarian, Ph.D. Department of Pharmaceutical Sciences. Western University of Health Sciences ... Charles Drew University. Dr. Theodore Friedman. Funds ... – PowerPoint PPT presentation

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Title: Arbi Nazarian, Ph'D'


1
The Effects of Acetaminophen on the Rewarding
Properties of Hydrocodone in Rats
  • Arbi Nazarian, Ph.D.
  • Department of Pharmaceutical Sciences
  • Western University of Health Sciences
  • Pomona, CA

2
Prescription Opioid Analgesics
  • The Good
  • Prescription opioid analgesics (e.g. Vicodin,
    Oxycontin, Percodan) have been used for many
    years for the treatment of moderate to severe
    pain.
  • Quite a few of these analgesics are cocktail
    formulations of 2 compounds an opioid agonist
    (narcotic) , such as hydrocodone, oxycodone or
    tramadol a non-narcotic analgesic, such as
    acetaminophen, ibuprofen or aspirin.
  • Vicodin Hydrocodone Acetaminophen
  • Percodan Oxycodone Aspirin
  • Initial intent for the use of cocktail
    formulations Reduce amount of narcotic, to
    reduce risk of side effects, yet reach good
    analgesic efficacy.

3
Prescription Opioid Analgesics
  • The Bad
  • Use of Opioid analgesics can leads to complex
    side effects
  • Respiratory Depression
  • Constipation
  • Analgesic Tolerance
  • Physiological Dependence
  • Psychological Dependence/Addiction

4
Prescription Opioid Analgesics
  • The Ugly
  • Non-medical, illicit use of opioid analgesics is
    on the rise.
  • In 2006, 5.2 million
  • people in the U.S. used
  • analgesics in a
  • non-medical context.
  • (NSDHU, 2007)

SAMHSA 2002
5
Prescription Opioid Analgesics
  • Most prevalent in adolescents and young adults.
    (MTF, 2007)

6
Cocktail formulation most commonly used in
nonmedical context
SAMHSA, 2002
7
Why so much nonmedical use?
  • Ease of access.
  • Is that it?
  • Can some cocktail formulations possess greater
    rewarding effects than the opioid agonist alone?

8
Could Hydrocodone Acetaminophen have greater
rewarding properties as compared to Hydrocodone,
alone?
  • Experimental Approach
  • Measure the rewarding effects of hydrocodone.
  • Measure the rewarding effects of acetaminophen
  • Measure the rewarding effects of hydrocodone
    acetaminophen.
  • All experiments conducted in rats.

9
How to measure drug reward in a rat?
  • Conditioned place preference (CPP)
  • Rats injected with drug or saline in a distinct
    compartment over 4 conditioning, days.
  • Place preference
  • measured on post-
  • conditioning test day
  • in a drug free state.
  • CPP amount of time
  • spent on the drug-
  • paired side vs. saline-
  • paired side.

10
Results- Hydrocodone produced CPP in rats
11
Results- Acetaminophen did not produce CPP in rats
12
Results- Acetaminophen enhanced hydrocodone CPP
13
Results- Acetaminophen did not enhance
hydrocodone-induced locomotor activity
Acute Locomotor Activity (Day 1)
Conditioned Locomotor Activity (Test Day)
14
Summary
  • Rats developed a CPP to hydrocodone (5.0 mg/kg).
  • Rats did not develop a CPP to acetaminophen
  • Rats developed a CPP to a combination of
    acetaminophen and a non-CPP producing dose of
    hydrocodone.
  • Acetaminophen did not enhance the locomotor
    activating effects of hydrocodone

15
Work in Progress
  • Studying other doses of acetaminophen.
  • Investigating potential mechanisms.

16
Many Thanks
  • Western University
  • Deepthi Are
  • Meagan Parker
  • Yelba Carrillo
  • Erika Estrada
  • Consultant
  • Dr. Kabir Lutfy
  • Charles Drew University
  • Dr. Theodore Friedman
  • Funds Provided by
  • Western University College of Pharmacy
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