1. Opiates
Lesson 17

2. Opiates Alkaloids from opium poppy Opium extract 0.5% codiene
20% morphine
alter structure  heroin
Opioids: synthetic analogs (texts)
Major effects: Analgesia & Euphoria ~

3. Opiate Family Large family of drugs neuropeptides
morphine is prototype
Difference is potency
compare to morphine = 1 ~

4. Relative Potency Opiate Potency Morphine 1 Methadone 1
Propoxyphene (Darvon)
Codeine
Meperidine (Demerol)
Oxycodone (Oxycontin, Percodan)
Heroin
Fentanyl ~

5. Pharmacokinetics Route: sc, im, iv p.o. not as effective
ion trapping
1st pass metabolism
Significant brain levels: min
immediate euphoria?
Conditioned effects ~

6. Pharmacokinetics Half-life: about 3 hrs Duration of effects: 4-5 hrs
then withdrawal begins
Heroin: crosses BBB more easily
diacetylmorphine
biotransformed into morphine
Codiene:
10% transformed to morphine ~

7. Opiate Effects Analgesia Euphoria Respiratory Depression Narcosis
drowsiness ~

8. Opiate Effects Antitussive Constipation Impotence & reduced libido
inhibits coughing
Constipation
Impotence & reduced libido
Reduced aggression & social interaction
opioid role in social bonds
Alters food intake, BT, etc. ~

9. Opioid Receptors Areas Mapped (1970s) Pain Pathways:
Periaqueductal Gray (PAG),
Dorsal Horn Spinal Cord
Also:
Hypothalamus
G. I. Tract,
Limbic System (VTA, Nucleus Accumbens)
Medulla ~

10. Opioid Receptors 2d messenger systems Open K+ channels
hyperpolarization
Close Ca++ channels
decreased NT release
Inhibits adenylyl cyclase
 cAMP ~

11. Opioid Receptors: Subtypes
m (mu)
m1 –  supraspinal & spinal analgesia
m2 –  respiration,  HR, euphoria
d (delta)
Modulates m analgesia, positive RFT
k (kappa)
spinal analgesia, pain perception
sedation, dysphoria, hallucinations
gut motility, body temperature ~

12. Endorphins Peptide Family: Hormones, Neuromodulators & NTs
b -Endorphin
Met- & Leu-Enkephalin
Dynorphin ~

13. Euphoria & Reward Ventral Tegmental Area (VTA) opioid neurons
dopamine neurons
GABA neurons?
hypothesized
GABA inhibits DA neurons
Opioids inhibit GABA neurons ~

14. Nucleus
Accumbens
VTA
Opioid -
GABA - DA

15. Other Opioid-Mediated Behaviors
Social Bond Formation
Various abnormal behaviors
Schizophrenia
Infantile Autism
Self-Mutilation ~

16. Opiate Problems High Dependence Liability
Positive & Negative Reinforcer
Withdrawal Symptoms
Tolerance & Cross Tolerance
Different rates for various effects
Euphoria: fast
Respiratory depression: slow ~

17. Opiate Dependence: Treatment
2007 National Survey on Drug Use and Health: heroin use / oxycodone
past year: 366, 000 / 1.4 million
past month 153,000 / 369,000
Methadone Treatment
taken p.o.
half-life about 36 hrs
 euphoria & blocks withdrawal
develop methadone dependence ~

18. Opiate Dependence: Treatment
LAAM: L-alpha-acetylmethadol
(Orlaam)
half-life 2-6 days
slightly more treatment dropouts
not recommended for women of child-bearing age
*Buprenorphine (Subutex)
 craving
*Buprenorphine + naloxone (Suboxone)
 craving & rewarding effects ~