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Opioids/Opiates
Narcotics: (Opioids)
These drugs are referred to as
the opioid (or opiate) narcotics
because of their association
with opium
Opioids
Compounds with opiate-like
actions, including, but not
confined to opiates (e.g.,
synthetic, endogenous
opioids)
Opiates
 alkaloids
found in the
opium poppy
(Papaver
somniferum)
 [Gk. opion =
“poppy juice”]
Types of opioids
1. Naturallyoccurring
opium
 sap from
opium poppy

Two major active
alkaloids
morphine
 codeine

What are narcotics?

The term narcotic
currently refers to
naturally
occurring
substances
derived from the
opium poppy and
their synthetic
substitutes.
What are narcotics?


For the most part, the
opioid narcotics
possess abuse potential,
but they also have
important clinical value
(analgesic, antitussive).
The term narcotic has
been used to label many
substances, from opium
to marijuana to cocaine.
Morphine


Morpheus (god of Dreams)
-son of Hypnos
~ 10% of opium
by weight
N
CH 3
H
HO
O
Morphine
OH
Pharmacological effects



Morphine is a particularly potent pain
reliever and often is used as the analgesic
standard by which other narcotics are
compared.
With continual use, tolerance develops to
the analgesic effects of morphine and other
narcotics.
Physicians frequently underprescribe
narcotics, because of fear of causing
narcotic addiction.
Codeine


methylmorphine
~ 0.5% of
opium
Semi-synthetics
Semi-synthetics
Heroin




diacetylmorphine
addition of two acetyl groups to morphine
~ 10x more potent than morphine
pharmacological effect usually thought to be
identical to morphine
 in brain: heroin > morphine
(new data suggest morphine and heroin
may have different actions; 1999)
Semi-synthetic analgesics



Hydromorphone (Dilaudid®)
Hydrocodone (Hycodan®)
Oxycodone (Percodan®)
Synthetics
Phenylpiperidines
 Fentanyl “china white”
 Meperidine (Demerol®)
(MPPP)
Methadone & Congeners
 Methadone (Dolophine®)
 Propoxyphene
(Darvon®)
Benzomorphans
 Pentazocine (Talwin®)
N
CH 3
C
O
CH 2
CH 3
O
Pethidine
(Meperidine)
H 3C
N
H
C
(CH 3)2
CH 2
O
Methadone
CH 3
Analgesic potency
Analgesic
Mild to moderate pain
potency
codeine, propoxyphene (Darvon®)
Moderately severe pain
meperdine (Demerol®)
Severe pain
heroin, hydromorphone (Dilaudid®)
Endogenous opioids


Enkephalins, endorphins and dynorphins
Morphine & codeine?
History of use - opium
Since recorded
history
Ingredient in all
sorts of medicinal
preparations
History of use - morphine
“Soldiers disease”
History of use
Ads for heroin
Analgesia
Heroin vs. Morphine

difference pharmacokinetic?

recent evidence for different receptors
- MOR-1 knockouts
Reinforcing effects
Reinforcing effects

All classical opioid drugs of abuse have a preference
for µ sites (e.g., morphine, heroin, methadone,
fentanyl etc.)
  may contribute, but little known

 compounds are not self-administered
 psychomimetic and aversive in humans
The history of narcotics
The history of narcotics







A 6,000-year-old Sumerian tablet
The Egyptians
The Greeks
Arab traders
China and opium trade
The Opium War of 1839
American opium use
Abuse, tolerance, dependence,
and withdrawal

All the opioid narcotic agents that activate opioid
receptors have abuse potential and classified as a
schedule drugs.

An estimated 2.5 million people in the U.S abuse
heroin or other narcotics.

Tolerance begins with the first dose of a narcotic,
but does not become clinically evident until 2 to 3
weeks of frequent use.
Abuse of opioid narcotics




Tolerance occurs most rapidly with high doses
given in short intervals.
Doses can be increased as much as 35 times in
order to regain the narcotic effect.
Physical dependence invariably accompanies
severe tolerance.
Psychological dependence can also develop
with continual narcotic use.
Heroin Abuse




Heroin is classified as a Schedule I drug.
Heroin is the most widely abused illegal
drug
in European and Far Eastern
countries.
Heroin was illicitly used more than any
other drug of abuse in the U.S. (except for
marijuana) until 15 years ago, when it was
replaced by what drug?
Cocaine
Heroin combinations





Pure heroin is a white powder
Heroin is usually “cut” (diluted) with
lactose
When heroin 1st enters the U.S., it may be
95% pure, by the time it is sold, it is 3 to 5%
pure
Heroin has a bitter taste and often cut with
quinine
Heroin and fentanyl (Tango and Cash or
Goodfellas)
Heroin jeopardy
A. Approximately 3,000 to 4,000 deaths
Q. How many deaths occur annually in the
United States from heroin overoses?
A. 500,000 to 750,000
Q. What is the estimated number of heroin addicts in
the United States
A. These locations serve as gathering places for
addicts
Q. What are “shooting galleries”?
Stages of dependence



When narcotics such as heroin are first
used by people not experiencing pain, the
drugs can cause unpleasant, dysphoric
sensations.
Euphoria gradually overcomes the aversive
effects.
The positive feelings increase with narcotic
use, leading to psychological dependence.
Stages of dependence
 After
psychological dependence,
physical dependence occurs with
frequent daily use, which
reinforces ant narcotic abuse.
 If the user stops taking the drug
after physical dependence has
occurred severe withdrawal
symptoms result.
Methods of administration





Sniffing the powder (insufflating)
Injecting it into a muscle (intramuscular)
Smoked
Mainlining (intravenous injection)
Heroin addicts and AIDS
40 to 50% of IV heroin users have been
exposed to the AIDS virus
Withdrawal symptoms
After the effects of the heroin wear off,
the addicts has only a few hours in
which to find the next dose before
severe withdrawal symptoms begin.
 A single “shot” of heroin lasts 4 to 6
hours
 Withdrawal symptoms - runny nose,
tears, minor stomach cramps, loss of
appetite, vomiting, diarrhea, abdominal
cramps, chills, fever, aching bones,
muscles spasms

Other narcotics









Morphine
Methadone
Fentanyl
Hydromorphone
Meperidine
MPTP
Codeine
Pentazocine
Propoxyphene
Narcotic-related drugs
Dextromethorphan
Clonidine
Naloxane
Major effects
Analgesia

Relief of pain in absence of impairment in
other sensory modalities
Euphoria - Pleasure

Produce sense of well being, reduce
anxiety, positive feelings
Other effects
Nausea & vomiting
 Respiratory depression
 Miosis
 Gastrointestinal effects
 Cough Suppression
 Motor effects

Sensitization
 Psychomotor
stimulant effects
 Rewarding effects
(conditioned place preference)
Analgesia
Spinal actions


Dorsal horn
of spinal cord
primary pain
afferents
Dorsal
horn
Ventral
horn
4.2
Analgesia
Spinal actions

inhibit incoming pain signals
Projection
neuron
Opioid receptor
Sensory
neuron
+
Spinal
cord
12.8