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Chapter 13

Opioids

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Opium is a naturally occurring substance derived from the poppy plant

Papaver somniferum

Opium has a 6,000-year history of medical use

Opioids are either:

Drugs derived directly from opium or

Synthetic drugs with opium-like effects

Major effects of opioids:

relieves pain and suffering

delivers pleasure and relief from anxiety

Opioids

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Opium is collected for only a few days of the plant’s life

Opium harvesters make shallow cuts into the unripe seedpods

The resinous substance that oozes from the cuts is scraped and collected

Opium products

Morphine extracted from raw opium

Heroin is derived from morphine

Opium Cultivation

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Image Source: © Botonica/ JupiterImages/Getty Images

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Egypt

1500 BC: Ebers papyrus described medical uses

Greece

Had an important role in medicine

Arabic world

Opium used as a social drug

Physicians wrote widely about use of opium and described opioid addiction

History of Opium

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Europe

Opium used widely beginning in the 16th century

Physicians developed a preparation called laudanum, a combination of strained opium and other ingredients

Writers and Opium

1821: Thomas De Quincey “Confessions of an English Opium-Eater”

Elizabeth Barrett Browning and Samuel Taylor Coleridge famously used opium

History of Opium

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The Opium Wars

1729: Opium smoking outlawed in China

But smuggling was widespread

British East India Company was involved in opium trade

Legally in India and illicitly (but indirectly) in China

Pressure grew and eventually war broke out between the British and Chinese

History of Opium

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Morphine is the primary active ingredient in opium

First isolated in 1806

Named morphium after Morpheus, the god of dreams

10 times as potent as opium

Codeine is a secondary active alkaloid

First isolated in 1832

Named codeine from the Greek word for “poppy head”

Morphine

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Morphine use spread due to two developments

Technological development:

1853: Hypodermic syringe allowed delivery of morphine directly into the blood

Political development:

Widespread use during war provided relief from pain and dysentery

Veterans returned addicted to morphine

Addiction was later called “soldier’s disease” or “army disease”

Morphine

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Heroin = diacetylmorphine

1874: two acetyl groups were attached to morphine

1898: marketed as Heroin (brand name) by Bayer

Three times as potent as morphine

due to increased lipid solubility of the heroin molecule

Originally marketed as a non-addictive cough suppressant

Replacement for codeine and morphine

Later linked to addiction

Heroin

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Three types of opioid dependence in the U.S.:

Oral intake via patent medicines

Opium smoking mostly by Chinese laborers

Injection of morphine

the most dangerous form of use

Opioid Abuse Before Harrison Act

% of population addicted to opioids
Peaked at the start of 20th century
Possibly as high as 1% of the population

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Image source (opium den): Library of Congress Prints and Photographs Division (Image Ch13_13OpiumDen)

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Initially, opioid dependence was not viewed as a major social problem

Opium smoking was limited to certain ethnic groups

Patent medicines were socially acceptable

Opioid addiction was viewed as a “vice of middle life”

Typical user:

30 to 50-year-old middle class white woman

Drugs purchased legally in patent medicines

Opioid Abuse Before Harrison Act

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Enforcement of the 1914 Harrison Act made opioids difficult to obtain

Only sources of drugs were illegal dealers

Resulted in changes in opioid use patterns

Oral use declined

Primary remaining group of users were those who injected morphine or heroin

Cost and risk of use increased

Thus, the most potent method (intravenous injection of heroin) was favored

Addicts were looked upon as criminals rather than as victims

Opioid Abuse After Harrison Act

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After WWII

Use of heroin increased in low-income areas of large cities

The 1960s and 70s

Heroin use further increased in large cities

Heroin use was associated with minority populations

In New York, users were prosecuted under the Rockefeller Drug Laws

Strictest drug laws in U.S.

Opioid Abuse After Harrison Act

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Image source: © Medio Images/PictureQuest (Image Ch13_16InjectArm2)

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Heroin in Vietnam was relatively

Inexpensive

Pure

Easy to obtain

About 5% of personnel tested positive for opioids

Due to the purity, most users smoked or sniffed the drug

Most users stopped when they returned to the U.S.

Vietnam experience showed

Under certain conditions, a relatively high percent of individuals will use heroin recreationally

Heroin addiction is not inevitable among occasional users

Heroin Use in Vietnam

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Heroin Production and Purity

Most of the heroin used in the U.S. is derived from poppies grown in Mexico and Colombia

Purity of heroin has increased dramatically in recent years

Mid-1970s: purity was 5%

1980s: 25%

Currently: 20–40%

Important note: few Americans use heroin

0.2% report past-year use

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Popular prescription opioids

Hydrocodone (Vicodin, Lortab)

Oxycodone (OxyContin, Percocet)

Prevalence of use:

2012: 2% of Americans 12 and older reported past month use

Routes of administration include oral, insufflation, injection

Safety concerns:

DAWN data: prescription opioids rank 3rd for ER visits and 1st for deaths

Most opioid overdoses occur in combination with other sedatives such as alcohol

Abuse of Prescription Opioids

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Opioid Chemical Characteristics

Narcotic agents isolated or derived from opium

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Figure 13.1 from text

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Natural products

Morphine

Codeine

Semisynthetics

Heroin

Synthetics

Methadone

Meperidine

Oxycodone

Oxymorphone

Hydrocodone

Hydromorphone

Dihydrocodeine

Propoxyphene

Pentazocine

Fentanyl

Prescription Narcotic Analgesics

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Naturally occurring opioid-like neurotransmitters

Enkephalins: morphinelike neurotransmitters found in the brain and adrenals

Endorphins: morphinelike neurotransmitters found in the brain and pituitary gland

Endogenous opioids and opioid drugs are agonists of several types of opioid receptors

mu and kappa (play a role in pain perception)

delta (function not well understood)

Mechanism of Action

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Drugs that block the action of opioids

Examples: Naloxone (Narcan) and nalorphine

Effects

Reverse depressed respiration from opioid overdose

Precipitate withdrawal syndrome

Prevent dependent individuals from experiencing a high from subsequent opioid use

Harm reduction strategy

Several U.S. cities have initiated programs that provide naloxone to heroin users

Results in fewer overdose deaths

Opioid Antagonists

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Pain relief

Reduces the emotional response to pain

Diminishes the patient’s awareness of, and response to, the aversive stimulus

Typically causes drowsiness but does not induce sleep

Treatment of intestinal disorders

Counteracts diarrhea and the resulting dehydration

Decreases number of peristaltic contractions

Cough suppressant

Codeine has long been used for its antitussive properties

Dextromethorphan (OTC antitussive) is an opioid analogue

Beneficial Uses

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Tolerance

Tolerance develops to most effects

Higher doses needed to maintain effects

Cross-tolerance exists among all the opioids

Physical dependence

Opioid withdrawal is unpleasant but rarely life-threatening

Withdrawal symptoms can be prevented with any opioid agonist

Dependence Potential

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Approximate hours after previous dose

Opioid Withdrawal Symptoms

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Signs	Heroin or Morphine	Methadone
Craving for drugs, anxiety	6	24
Yawning, perspiration, running nose, teary eyes	14	34-48
Increase in above signs plus pupil dilation, goose bumps, tremors, hot and cold flashes, aching bones and muscles, loss of appetite	16	48-72
Increased intensity of above, plus insomnia; raised blood pressure; increased temperature, pulse rate, respiratory rate and depth; restlessness; nausea	24-36
Increased intensity of above, plus curled-up position, vomiting, diarrhea, weight loss, spontaneous ejaculation or orgasm, hemoconcentration, increased blood sugar	36-48

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Fast-acting injectable opioids are most likely to lead to dependence

Dependence Potential

Psychological dependence

Positive reinforcement

Positive effects reliably follow use of the drug

Negative reinforcement

Use of the drug removes withdrawal symptoms

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Acute toxicity

Opioids depress respiration

Effects with alcohol are additive

Occasionally, nausea and vomiting

Can be counteracted with naloxone

Chronic toxicity

Associated with injection

Infections and the spread of blood-borne diseases

Toxicity Potential

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“No Vacation”

Three to four injections needed daily to prevent withdrawal

Expensive habit

cost of drugs and paraphernalia

Health concerns

Risk of overdose due to variable potency of different batches

Skin infections

Blood-borne infections

Important note: A large number of heroin users “mature out”

Gradually stop using the drug

Life of a Person Addicted to Heroin

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Intense pleasure unequaled by any other experience

Some people report nausea and discomfort but continue to use

Then, tolerance to negative effects develops more rapidly compared to euphoric effects

Withdrawal is always excruciating

Withdrawal is often similar to a mild case of the intestinal flu

After one injection you are hooked for life

Becoming dependent takes time and persistence

Misconceptions

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