“Narcotic Analgesics”
(Opiates or Opioids)

u Natural source = Papaver somniferum

l raw opium, contains:

l *morphine (“prototype” of a narcotic)(extracted in 1803; named after Greek god of dreams)

l *codeine (1/10-1/12 as potent as morphine)

Beware of the term “narcotics” as used by law enforcement/drug enforcement agencies- it is not the same as the pharmacological category

Chemically Altered Naturals
or Semi-synthetic Opiates

u *heroin (2-3 x as potent as morphine)

u *oxycodone (Percodan, Oxycontin (a timed-release form lasting 12 hrs)

u hydromorphone (Dilaudid) (6-10 x)

Codeine

u Most widely used medical narcotic because of its lower potential for abuse (but still can induce dependency)

Totally Synthetic Narcotics

u *methadone (Dolophine) =

u *mepiridine (Demerol) (1/10-1/5)

u *propoxyphene (Darvon) (1/15)

u *LAAM

u pentazocine (Talwin)

u *fentanyl (Sublimaze) (100x)

u *A variety of street analogs of fentanyl and mepiridine (“designer drugs”)

Narcotics may be administered by any route but intensity of effect varies (I.V & smoking most intense)

Main effects

u Euphoria

u Sedation

u Constipation, nausea

u Analgesia

u Pupil constriction

u Eliminates cough

u Slows respiration

Medical Uses for Opiates

u Our strongest analgesics

u Antitussive (anti-cough)

u Treat diarrhea

u Detoxification of narcotic addicts

Endogenous Morphine-Like Substances & Opiate Receptors”

u Our bodies produce their own pain relieving, euphoria producing substances (endorphins, enkephalins, dynorphins) which act on specific receptors (opioid receptors, several varieties).

u Narcotic analgesics work because they can also activate these receptors, especially the mu variety of receptors

u Substances which fully activate the receptors = “pure agonists”, substances that weakly activate receptors = “partial agonists”

Location of Opioid Receptors

Reward Pathway

Antagonists

u Some drugs fit receptors but have little or no action (“narcotic antagonists”) but do prevent other opioids from activating the receptors.

u Substances which fully block receptors = “pure antagonists”

u There are also weak (partial) antagonists and substances that have mixed agonist/antagonist effects.

Opiate Use in the US

u unregulated before 1900’s

u 1800’s -sold by Sears, drug stores, mail order and by traveling salesmen selling patent medicines

u most common users were middle class women; even children were given opiates to sooth teething etc.

u hypodermic invented in 1856 - opiates were widely used during the Civil War to relieve pain as well as diarrhea

History (continued)

u 1898 Bayer Labs introduced heroin as a non-addicting substitute for codeine

u (in 1957 similar claims made for Darvon)

u by 1900 ~250,000-750,000 Americans using opiates (a higher proportion of population than today’s ~300,000-500,000)

u after Harrison Act of 1914 demographics of use changed (use of black market drugs by urban males)

Medical Narcotic Analgesics

u Narcotic analgesics are not debilitating or toxic themselves (no organ damage).

u Those using narcotics for chronic pain do not suffer adverse effects on their health.

u Doctors often under-prescribe pain relievers for those in serious pain.

Heroin Abuse Risks

u Street drug risks:

l unknown dose; risk of toxic impurities

l don’t know what it is cut or mixed with

u Route of administration risks

l dirty needles transmit disease

l inflamed, infected, collapsed veins

l risk of injecting dirty drug

u Muffled body warning system

u Tolerance decreases safety margin

u Cost promotes illegal activities

Example of the Harm Reduction Approach: Needle Exchange

Narcotic Withdrawal

u Dysphoria and intense craving for relief

u Insomnia, irritability, restless

u Sniffles, shits, vomits

u Muscle spasms (“kicking the habit”)

u Agony, cramps, bone & muscle pain

u Yawns, shivers,stimulates hypothalamus

u Not life-threatening except in very rare cases

Pharmacologically assisted gradual withdrawal

u Milder symptoms if withdrawal is gradual

u Substitute a legal, oral narcotic (methadone or Demerol) & decrease dose over days

u In mild addictions non-narcotics may be sufficient (clonidine, a benzodiazepine to ease symptoms)

Rapid Detox

u Under general anesthesia addict given sufficient antagonist (like naloxone) to block all opiate receptors and withdraw the user within hours

u Clonidine is given to prevent hypertension

u (Normally narcotic antagonist would cause an extreme withdrawal)

Post-Detox Use of Narcotic Antagonist

u With antagonist in the system, if recovering addicts slips up and uses they will not experience the pleasurable narcotic effects

u Naltrexone (ReVia) provides a “crutch” for motivated individual.

Another Use for Antagonists

u Naloxone (Narcan) can immediately reverse a narcotic overdose, or the effects of narcotics on a baby born to a mother who is using

u Has a shorter time course than the drugs it is blocking so may need to be readministered

Methadone Maintenance

u Provide a safe, cheap source of narcotics to avoid health problems and many of the social problems; maintain daily contact

u Many maintenance programs require regular counseling as well and urine checks

u Methadone is effective orally and only needs to be taken once a day

u If user seems stable they may be given a few days worth of methadone

u LAAM only needs to be taken 3 times/week; buprenorphine is another option

u Some users drop out- miss rush & the culture

Methadone Maintenance

Non-Pharmacological Approaches

u Therapeutic community (live-in facility typically manned by former users)(Synanon, Daytop Village, Phoenix House, Gateway House)

u Outpatient counseling

u Self-help groups like Narcotics Anonymous

u Key: keeping person in treatment

u Some spontaneous “maturing out”