Opioids/Opiates

Narcotics: (Opioids)

These drugs are referred to as These drugs are referred to as the opioid (or opiate) narcotics the opioid (or opiate) narcotics because of their association because of their association with opiumwith opium

OpioidsOpioids

Compounds with opiate-like Compounds with opiate-like actions, including, but not actions, including, but not confined to opiates (e.g., confined to opiates (e.g., synthetic, endogenous synthetic, endogenous

opioidsopioids))

Opiates Opiates

alkaloids alkaloids found in the found in the opium poppy opium poppy (Papaver (Papaver somniferum)somniferum)

[Gk. opion = [Gk. opion = “poppy juice”]“poppy juice”]

Types of opioidsTypes of opioids

1. Naturally-1. Naturally-occurring occurring opium opium sap fromsap from

opium poppyopium poppy

Two major activeTwo major activealkaloidsalkaloids morphinemorphine codeinecodeine

What are narcotics?

The term The term narcoticnarcotic currently refers to currently refers to naturally naturally occurring occurring substances substances derived from the derived from the opium poppy and opium poppy and their synthetic their synthetic substitutes.substitutes.

What are narcotics?

For the most part, the For the most part, the opioid narcotics opioid narcotics possess abuse potential, possess abuse potential, but they also have but they also have important clinical value important clinical value (analgesic, antitussive).(analgesic, antitussive).

The term The term narcoticnarcotic has has been used to label many been used to label many substances, from opium substances, from opium to marijuana to cocaine.to marijuana to cocaine.

MorphineMorphine

Morpheus (god of Dreams)Morpheus (god of Dreams)

-son of Hypnos-son of Hypnos ~ 10% of opium~ 10% of opium

by weightby weight

HO O OH

N CH3

H

Morphine

Pharmacological effects

Morphine is a particularly potent pain Morphine is a particularly potent pain reliever and often is used as the analgesic reliever and often is used as the analgesic standard by which other narcotics are standard by which other narcotics are compared.compared.

With continual use, tolerance develops to With continual use, tolerance develops to the analgesic effects of morphine and other the analgesic effects of morphine and other narcotics.narcotics.

Physicians frequently underprescribe Physicians frequently underprescribe narcotics, because of fear of causing narcotics, because of fear of causing narcotic addiction.narcotic addiction.

CodeineCodeine

methylmorphinemethylmorphine ~ 0.5% of~ 0.5% of

opiumopium

Semi-synthetics Semi-synthetics

Semi-syntheticsSemi-synthetics

HeroinHeroin diacetylmorphinediacetylmorphine addition of two acetyl groups to morphineaddition of two acetyl groups to morphine ~ 10x more potent than morphine~ 10x more potent than morphine pharmacological effect usually thought to be pharmacological effect usually thought to be

identical to morphineidentical to morphine in brain: heroin > morphinein brain: heroin > morphine

(new data suggest morphine and heroin(new data suggest morphine and heroinmay have different actions; 1999)may have different actions; 1999)

Semi-synthetic analgesicsSemi-synthetic analgesics

Hydromorphone (Dilaudid®)Hydromorphone (Dilaudid®) Hydrocodone (Hycodan®)Hydrocodone (Hycodan®) Oxycodone (Percodan®)Oxycodone (Percodan®)

SyntheticsSynthetics

PhenylpiperidinesPhenylpiperidines Fentanyl “china white”Fentanyl “china white” Meperidine (Demerol®)Meperidine (Demerol®)

(MPPP)(MPPP)Methadone & CongenersMethadone & Congeners

Methadone (Dolophine®)Methadone (Dolophine®) Propoxyphene Propoxyphene

(Darvon®)(Darvon®)Benzomorphans Benzomorphans

Pentazocine (Talwin®)Pentazocine (Talwin®)

N CH3

CH2C O

O

CH3

Pethidine (Meperidine)

NH

(CH3)2

Methadone

CH2C

O

CH3

H3C

Analgesic potencyAnalgesic potency

Analgesic potency

Mild to moderate pain

Moderately severe pain

Severe pain

codeine, propoxyphene (Darvon®)

meperdine (Demerol®)

heroin, hydromorphone (Dilaudid®)

Endogenous opioidsEndogenous opioids

Enkephalins, endorphins and dynorphinsEnkephalins, endorphins and dynorphins Morphine & codeine?Morphine & codeine?

History of use - opiumHistory of use - opium

Since recorded Since recorded historyhistory

Ingredient in allIngredient in all

sorts of medicinalsorts of medicinal

preparationspreparations

History of use - morphineHistory of use - morphine

“Soldiers disease”

History of useHistory of use

Ads for heroinAds for heroin

AnalgesiaAnalgesia

Heroin vs. MorphineHeroin vs. Morphine

difference pharmacokinetic?difference pharmacokinetic?

recent evidence for different receptorsrecent evidence for different receptors- MOR-1 knockouts- MOR-1 knockouts

Reinforcing effectsReinforcing effects

Reinforcing effectsReinforcing effects

All classical opioid drugs of abuse have a preference All classical opioid drugs of abuse have a preference for µ sites (e.g., morphine, heroin, methadone, for µ sites (e.g., morphine, heroin, methadone, fentanyl etc.)fentanyl etc.) may contribute, but little knownmay contribute, but little known

compounds are not self-administeredcompounds are not self-administered psychomimetic and aversive in humanspsychomimetic and aversive in humans

The history of narcotics

The history of narcotics

A 6,000-year-old Sumerian tabletA 6,000-year-old Sumerian tablet The EgyptiansThe Egyptians The GreeksThe Greeks Arab tradersArab traders China and opium tradeChina and opium trade The Opium War of 1839The Opium War of 1839 American opium useAmerican opium use

Abuse, tolerance, dependence, and withdrawal

All the opioid narcotic agents that activate opioid All the opioid narcotic agents that activate opioid

receptors have abuse potential and classified as a receptors have abuse potential and classified as a

schedule drugs.schedule drugs.

An estimated 2.5 million people in the U.S abuse An estimated 2.5 million people in the U.S abuse

heroin or other narcotics.heroin or other narcotics.

Tolerance begins with the first dose of a narcotic, Tolerance begins with the first dose of a narcotic,

but does not become clinically evident until 2 to 3 but does not become clinically evident until 2 to 3

weeks of frequent use.weeks of frequent use.

Abuse of opioid narcotics

Tolerance occurs most rapidly with high doses Tolerance occurs most rapidly with high doses given in short intervals.given in short intervals.

Doses can be increased as much as 35 times Doses can be increased as much as 35 times in order to regain the narcotic effect. in order to regain the narcotic effect.

Physical dependence invariably accompanies Physical dependence invariably accompanies severe tolerance.severe tolerance.

Psychological dependence can also develop Psychological dependence can also develop with continual narcotic use.with continual narcotic use.

Heroin Abuse

Heroin is classified as a Schedule I drug.Heroin is classified as a Schedule I drug. Heroin is the most widely abused illegal Heroin is the most widely abused illegal

drug drug in European and Far Eastern countries.in European and Far Eastern countries. Heroin was illicitly used more than any Heroin was illicitly used more than any

other drug of abuse in the U.S. (except for other drug of abuse in the U.S. (except for marijuana) until 15 years ago, when it was marijuana) until 15 years ago, when it was replaced by what drug?replaced by what drug?

Cocaine Cocaine

Heroin combinations

Pure heroin is a white powderPure heroin is a white powder Heroin is usually “cut” (diluted) with Heroin is usually “cut” (diluted) with

lactoselactose When heroin 1st enters the U.S., it may be When heroin 1st enters the U.S., it may be

95% pure, by the time it is sold, it is 3 to 95% pure, by the time it is sold, it is 3 to 5% pure5% pure

Heroin has a bitter taste and often cut with Heroin has a bitter taste and often cut with quininequinine

Heroin and fentanyl (Heroin and fentanyl (Tango and Cash Tango and Cash or or GoodfellasGoodfellas))

Heroin jeopardy

A. Approximately 3,000 to 4,000 deaths A. Approximately 3,000 to 4,000 deaths

Q. How many deaths occur annually in the Q. How many deaths occur annually in the United States from heroin overoses?United States from heroin overoses?

A. 500,000 to 750,000A. 500,000 to 750,000

Q. What is the estimated number of heroin addicts in Q. What is the estimated number of heroin addicts in the United Statesthe United States

A. These locations serve as gathering places for A. These locations serve as gathering places for addictsaddicts

Q. What are “shooting galleries”?Q. What are “shooting galleries”?

Stages of dependence

When narcotics such as heroin are first When narcotics such as heroin are first used by people not experiencing pain, the used by people not experiencing pain, the drugs can cause unpleasant, dysphoric drugs can cause unpleasant, dysphoric sensations.sensations.

Euphoria gradually overcomes the aversive Euphoria gradually overcomes the aversive effects.effects.

The positive feelings increase with narcotic The positive feelings increase with narcotic use, leading to psychological dependence.use, leading to psychological dependence.

Stages of dependence

After psychological dependence, After psychological dependence, physical dependence occurs with physical dependence occurs with frequent daily use, which reinforces frequent daily use, which reinforces ant narcotic abuse.ant narcotic abuse.

If the user stops taking the drug If the user stops taking the drug after physical dependence has after physical dependence has occurred severe withdrawal occurred severe withdrawal symptoms result.symptoms result.

Methods of administration

Sniffing the powder (insufflating)Sniffing the powder (insufflating) Injecting it into a muscle (intramuscular)Injecting it into a muscle (intramuscular) SmokedSmoked Mainlining (intravenous injection)Mainlining (intravenous injection)

Heroin addicts and AIDSHeroin addicts and AIDS 40 to 50% of IV heroin users have been 40 to 50% of IV heroin users have been

exposed to the AIDS virusexposed to the AIDS virus

Withdrawal symptoms

After the effects of the heroin wear off, After the effects of the heroin wear off, the addicts has only a few hours in the addicts has only a few hours in which to find the next dose before which to find the next dose before severe withdrawal symptoms begin.severe withdrawal symptoms begin.

A single “shot” of heroin lasts 4 to 6 A single “shot” of heroin lasts 4 to 6 hourshours

Withdrawal symptoms - runny nose, Withdrawal symptoms - runny nose, tears, minor stomach cramps, loss of tears, minor stomach cramps, loss of appetite, vomiting, diarrhea, abdominal appetite, vomiting, diarrhea, abdominal cramps, chills, fever, aching bones, cramps, chills, fever, aching bones, muscles spasmsmuscles spasms

Other narcotics

MorphineMorphine MethadoneMethadone FentanylFentanyl HydromorphoneHydromorphone MeperidineMeperidine MPTPMPTP CodeineCodeine PentazocinePentazocine PropoxyphenePropoxyphene

Narcotic-related drugs

Dextromethorphan Dextromethorphan

ClonidineClonidine

NaloxaneNaloxane

Major effectsMajor effects

AnalgesiaAnalgesia Relief of pain in absence of impairment in Relief of pain in absence of impairment in

other sensory modalitiesother sensory modalities

Euphoria - PleasureEuphoria - Pleasure Produce sense of well being, reduce Produce sense of well being, reduce

anxiety, positive feelingsanxiety, positive feelings

Other effectsOther effects

Nausea & vomitingNausea & vomiting Respiratory depressionRespiratory depression MiosisMiosis Gastrointestinal effectsGastrointestinal effects Cough SuppressionCough Suppression Motor effectsMotor effects

SensitizationSensitization

Psychomotor stimulant effectsPsychomotor stimulant effects Rewarding effectsRewarding effects

(conditioned place preference)(conditioned place preference)

AnalgesiaAnalgesiaAnalgesiaAnalgesia

Dorsal horn

Ventral horn

Dorsal root (sensory)

Ventral root (motor)

4.2

Spinal actionsSpinal actions Dorsal horn Dorsal horn

of spinal cordof spinal cord primary pain primary pain

afferentsafferents

Sensory neuron

Projection neuron

Spinalcord+

AnalgesiaAnalgesiaAnalgesiaAnalgesia

Spinal actionsSpinal actions inhibit incoming pain signalsinhibit incoming pain signals

Opioid receptor

12.8