Opiates & Opioid Narcotics

1. Opiates & Opioid Narcotics http://www.aurorawdc.com/ci/oxycontin.jpg http://www.pharmainfo.net/files/u4145/Morphine.jpg

2. Definitions • Opiates: drugs naturally found in opium (morphine and codeine) • Opioids: exogenous substances, natural or synthetic, with properties similar to opium • NARCOTICS: another term for opioids • This term was originally conceived to refer to substances that induce “narcosis” or sleep. • This term has been used more loosely in the legal profession to refer to all illicit drugs. • Technically, many of these drugs (e.g., cocaine, marijuana) are not narcotics according to the original definition of this term.

3. Early History of Opium • Papaver somniferum • Early Egyptian and Greek cultures • India and China • Opiate Dependence • 19th Century Writers and Opium • The Opium Wars • Started by outside incidents • Britain given the island of Hong Kong for winning

4. 19th Century Discoveries • Morphine isolated and named by Sertürner, 1806 • Codeine isolated in 1832 • Hypodermic syringe developed in 1853 by Alexander Wood • Heroin synthesized in 1874, marketed in 1898 by Bayer Laboratories http://www.pharmainfo.net/files/u4145/Morphine.jpg Photo from erowid.org

5. History of Opioid Use • Before the Harrison Act • Oral opium use common, patent medicines • ~ 1850, Chinese introduced opium smoking to U.S. • After 1850s, morphine administered by injection • 1898, heroin introduced • After the Harrison Act • Number of oral opium users declined • I.V. heroin injection became more common form of use among recreational users

6. History of Opioid Use • 20th Century Developments • Changing population of opioid users • 1960s • Vietnam and heroin use • 1970s-1980s • Current heroin use • Abuse of prescription opioids

7. Neuropharmacology of Opioids • Opioid Receptors • Mu, Kappa, Delta • Endogenous Opioids (Endorphins) • Enkephalins, Dynorphin, Beta-Endorphin • The activation of opioid receptors blocks the transmission of pain signals from the spinal cord and brain stem. • Opioid Antagonists • Naloxone • Naltrexone

8. Some Synthetic Opioids • methadone (Dolophine) • meperidine (Demerol) • oxycodone (Percodan) • oxymorphone (Numorphan) • hydrocodone (Vicodin, Lortab) • hydromorphone (Dilaudid) • propoxyphene (Darvon) • pentazocine (Talwin) • fentanyl (Sublimaze)

9. Medical Use of Opioids • Clinical Uses • Analgesics (pain relief) • Antidiarrheals (constipating effects) • Antitussives (cough suppressants) • Side Effects • Drowsiness • Respiratory depression • Nausea, vomiting, and constipation • Inability to urinate • Drop in blood pressure • Tolerance/Dependence • Physicians frequently under-prescribe narcotics, in fear of causing dependence.

10. Tolerance and Dependence with Opioids • Tolerance • begins with initial use, but not clinically evident until 2 to 3 weeks of frequent use. • occurs most rapidly with high doses given in short intervals. • Physical dependence • invariably accompanies severe tolerance • Psychological dependence • common with frequent narcotic use

11. Effects on Human Behavior • Subjective Effects (from anecdotal reports) • Opium was commonly used among 19th century literary figures and artists. • Effects depicted as euphoric, vivid dreamy, trance-like state. • Systematic Studies on Mood • Initial positive mood changes (anxiety reduction, euphoria), but continued use produces more negative mood states, social isolation, and aggression. • Subjective effects differ between experienced and naïve users. • Experience of pain influences subjective effects.

12. Effects on Human Behavior • Performance • In naïve subjects, opioids can slow performance on psychomotor tasks; cognitive performance is less impaired. • Tolerance develops to these effects in chronic users. • People can maintain good health and productive work for extended periods of opioid use. • Detrimental effects of opioids on performance are diminished when people are experiencing pain.

13. Behavioral Effects In Nonhuman Laboratory Studies • Unconditioned Behavior • Morphine has biphasic effects on spontaneous motor activity. • Low doses increase activity; higher doses decrease activity. • In rats, higher doses also produce stereotypy, which is distinct from the type of stereotypy produced by amphetamine. • e.g., wider range of behaviors, including social behaviors

14. Behavioral Effects In Nonhuman Laboratory Studies • Conditioned Behavior • Low doses of opioids increase response rates under schedules that produce low rates of responding (e.g., FI schedules) of positive reinforcement, but higher doses decrease rates. • Low doses increase avoidance responding; high doses slow avoidance responding without disrupting escape behavior (like the depressants). • Unlike depressants, opioids do NOT have antipunishment effects.

15. Self-Administration • Nonhuman animals readily acquire morphine and heroin self-administration. • Rates and patterns of self-administration are similar between humans and monkeys • Daily intake slowly increases over time and there are no periods of abstinence or voluntary withdrawal. • This is unlike patterns observed with cocaine self-administration, involving alternating cycles of intake and abstinence.

16. Drug Discrimination with Opioids • Most opioids are readily discriminated by nonhumans (rats and monkeys). • Stimulus generalization is observed between morphine and other mu agonists (e.g., heroin, methadone, codeine). • Partial generalization occurs between mu agonists and mixed agonists (e.g., cyclazocine). • Stimulus generalization generally not found between mu agonists and kappa agonists.

17. Health Risks • Abuse Potential • Subjective and reinforcing effects contribute to high abuse potential • MU agonists (e.g., morphine, heroin, fentanyl, hydrocodone, Oxycontin) tend to have a high abuse potential. • Mixed or partial agonists (e.g., butorphanol, nalbuphine) generally have low abuse potential. • I.V. Heroin Use and AIDS Risks • Over 50% of I.V. heroin users have been exposed to the AIDS virus

18. Opioid Dependence & Treatment • Withdrawal Symptoms (flu-like symptoms) • runny nose, tears, • minor stomach cramps, loss of appetite, vomiting, diarrhea, abdominal cramps, • chills, fever, aching bones, and muscle spasms • Narcotic Substitution Treatments • Methadone, levo-alpha acetylmethadol (LAAM), Buprenorphine • Maintaining dependence • Narcotic Antagonist Treatment • Naltrexone • Prevents user from experiencing high if opiates used • Compliance can be problematic.