OPIOIDS, ADDICTION, AND PAIN
From Review and Update of Pain and Palliative Medicine, presented by the University of California, Davis, Health
System
| OPIOIDS AND ADDICTION —Paul Kreis, MD, Associate Clinical Professor of Anesthesiology and
Pain Medicine, and Medical Director, Pain Program, University of California, Davis, School of Medicine,
Sacramento
|
| Introduction: difficult to remain neutral when patient exhibits aberrant behavior (eg, drug seeking); desire
to discharge patient from practice depends on personal perspective and experience with alcohol or substance
abuse (eg, substance abuse recovery possible, and process of recovery can enhance life vs family
member or friend killed by drunk driver or other violence associated with drug use); emotional reaction vs
clinical interpretation (addiction as disease); similar in many ways to diabetes (eg, genetic factors influence
susceptibility; inevitably progressive and fatal if untreated; requires ongoing input and management
on daily basis to maintain health, abstinence, and recovery)
|
| Patient concern: in 1962, ≈4 million Americans had tried illicit drugs (eg, marijuana, hallucinogens, cocaine,
heroin); in 1992, 80 million Americans had tried illicit drugs; 6 million (7.5%) had problems controlling
drug use (eg, creating problems in personal lives); in 1992, estimated cost to society of
alcoholism and drug abuse ≈$250 billion; 50% of cost for drug-related crimes (eg, driving under influence,
theft, assault); cohort study from 1998 found 80% of inmates in prison for offense related to drug
abuse (eg, selling drugs, crimes of passion while intoxicated, vehicular manslaughter)
|
| Societal concern: debate whether 1) pursuit of pleasure or happiness as primary goal philosophically justified;
or 2) happiness and pleasure byproducts of hard work (feel pleasure in job well done or because of
righteous suffering)
|
| Psychology of pleasure and pain: early theories—first described by Herbert Spencer; theorized pleasure
and pain actually survival mechanisms; coined term “survival of the fittest”; defined happiness as “net
greater amount of pleasure than pain”; BF Skinner used terms “reward” and “reinforcement”; felt
pleasure and pain reinforcing characteristics shaping behavior; posited that under right circumstances, he
could get group of individuals to do anything, depending on type of reinforcement; advertisers understand
behavior shaped by positive and negative reinforcement (much of which is unconscious or subconscious);
animal studies—brain mapping experiments in rats to find if part of brain subserved reward and
reinforcement (ie, pleasure and pain found in certain area of brain); ventral tegmental area important in
addiction; nucleus accumbens at center and loaded with dopaminergic terminals (entire ventral tegmental
tract dopaminergic, with links to limbic system and prefrontal cortex for future acquisition of reward);
analogous to human brain; every organism studied has reward and reinforcement circuitry
(discreet; can be identified through stimulation; motivation to eat and procreate advantageous to survival);
implications for humans—ablation of tremor in patients with Parkinson’s disease found related to
infarction in ventral medial thalamus; neurosurgeons hypothesized that ablation of ventral medial thalamus
could be therapeutic in patient with end-stage Parkinson’s disease who had no other treatments
available (before advent of computed tomography and magnetic resonance imaging); study found that
stimulation of nucleus accumbens in humans profoundly euphoric (analogous to intense orgasm; many
subjects had romantic attraction to surgeon after procedure)
|
| Role of reward circuitry in addiction: rat model measured changes in stimulation threshold in nucleus
accumbens; found that when rat self-administers morphine, nucleus accumbens becomes extremely sensitive
to electrical stimulation; inhibited by naloxone; similar for all substances of abuse (lowers threshold);
subsequent study found that any substance of abuse administered by rat resulted in increase in
concentration of dopamine in nucleus accumbens (final common pathway of euphoria; “we’re really
dopamine addicts, not dope addicts”); in both rat and human models, mu opioid input into nucleus accumbens
modulatory for all substances; explains why alcoholic patient prescribed naltrexone (blocks
opioid input into nucleus accumbens [“turns down sensitivity to all other input”]); opioid antagonist
attenuates euphoria for all substances of abuse; lesioning nucleus accumbens (severing tract between
ventral tegmental area and accumbens) in rats results in loss of interest in all substances of abuse; neurotransmitter
level—dopamine released into synaptic cleft then taken back up; addition of eg, cocaine, increases
amount of dopamine in synaptic cleft, and increases amount of synaptic activity; addition of
heroin increases sensitivity to dopamine; epiphenomena balances out, causing tremendous euphoric
“rush”
|
| Role of genetics in humans: risk of becoming alcoholic 40% to 50% related to genetics (more than environment);
percentage unknown for opiates; naltrexone and acamprosate recently available for treatment
of alcoholism; naltrexone attenuates euphoria from relapse; acamprosate attenuates environmental cue
response; 5 subtypes of dopamine receptors; accumbens primarily populated by D1, D2, and D3 receptors;
attempts made to block specific receptors to avoid dysphoria and depression (D1 and D2 receptors
involved in hedonic tone in nucleus accumbens); recent advance includes D3-receptor antagonist (inhibits
cocaine-seeking behavior in rats)
|
| TREATING PAIN —Steven H. Richeimer, MD, Chief, Division of Pain Medicine, and Associate Professor
of Anesthesiology and Psychiatry, Keck School of Medicine of the University of Southern California,
Los Angeles
|
| Successful legal cases: brought against clinicians for prescribing too freely or inadequately; also for not
advising about risks of opioids, turning patient into addict, or killing patient by overdose (inadequate supervision
by clinician); also well-known cases of clinicians inadequately prescribing for pain
|
| Recognizing effects on patient: determine whether patient at risk or already addicted; “not everything that
looks like addiction is addiction”; pseudoaddiction—patient looks and acts addicted, but really inadequately
treated for pain; becomes drug seeking and drug demanding to treat pain; in controlled environment,
give more medication; in pseudoaddiction, giving more drug effectively improves pain control and
patient appears less addicted (in contrast, addict deteriorates and appears more addicted); same treatment
more difficult in outpatient setting due to less control
|
| Rules for treating with narcotics: long-term prescribing may bring clinician under greater scrutiny, but
he or she should be able and willing to prescribe long term for benefit of patient; Intractable Pain Act
passed in California to allow physician to prescribe opioids for lifetime of patient; caveats—prescribe
controlled substance only to own patient (except when covering for another physician); chart with documented
history, physical examination (PE), and treatment plan used to prove patient yours; bridge dosing
allowed (72 hr in California) until patient’s physician returns; before prescribing long-term opioids, obtain
consultation from specialist in area of problem or from pain specialist; maintain flow sheet to document
evaluation and treatment history (note decision to increase dose in chart); inquiry system in place
for all schedule II prescriptions written for each patient in California; lists Drug Enforcement Administration
(DEA) numbers of all prescribing physicians (expanding to include schedule III drugs); patient’s
permission not required for inquiry
|
| Addiction: inappropriate seeking and use of drug; not tolerance or dependence; tolerance defined as needing
more drug over time to get same result; dependence defined as physical need in which sudden halt of
drug results in withdrawal (eg, long-term insulin use leads to tolerance and dependence); difficult situation
when patient has history of addiction but also has pain; give small doses, control tightly, and monitor
closely; use of consultant may be beneficial; do not prescribe opioids to active addict in uncontrolled
(ie, outpatient) setting; opioids cannot be prescribed if clinician believes they will be diverted and used
for another purpose; only choice to admit patient to manage pain
|
| Treatment agreements (opioid contracts): useful, but limiting; educational tool to teach patients what is
expected of them; speaker also uses for consent process; increasingly common requirement for patient
consent when placed on opioid therapy (may also be verbal); famous case (patient suicide) of physician
not documenting new treatment plan with rationale; speaker advises 1) document any change in treatment
plan, and 2) write agreements to be educational tools without indicating any clinical actions (course
of action should only be in treatment plan)
|
| Procedural complications: in pain procedures, nerve injury most common; pneumothorax injury also
common (primarily caused by trigger-point injections); coexisting disease may render patient unfit for
certain anesthesia block procedures (eg, bullous emphysema patient not good candidate for chest block);
neck block should not be bilateral; consider pneumothorax risks (eg, neck, shoulder, and mid back); case
findings—avoid heating pads (increase cutaneous blood flow up to 16-fold) in patient with, eg, fentanyl
patch or other transdermal drug delivery system; necessary to have “bullet proof” call system so patient
can reach clinician in emergency; undertreatment—as problematic as overtreatment; specific considerations
for avoiding litigation—always document history, PE, treatment plan, consent, special precautions,
and changes in treatment plan; consider problems with repetitive steroid dosing; monitor acetaminophen
intake; review consultation findings, laboratory results, and tests; know anatomy when performing
blocks (advance needle slowly; nerve damage main cause of lawsuits; warning signs occur prior to inflicting
much damage if needle moving slowly); similarly, advance drugs slowly
|
| Trusting patient: pain scale subjective; quality of pain data dependent on trustworthiness of patient; limiting
issues include secondary gain, lack of objective findings, lack of trust in judgment of patient (overcome
by talking with patient about trust from beginning [complete compliance may be key to
trustworthiness]); other signs of trustworthiness include patient effort to get better (eg, stress management,
physical therapy, exercise) and consistency (speaker gathers weekly with other clinicians to verify)
|
| Potential consequences of errors in pain management: medical board may suspend license, pending
further education and passage of test by examiner
|
Educational Objectives
| The goal of this program is to educate the listener about opioids and addiction and about ethical and legal issues
in treating pain. After hearing and assimilating this program, the participant will be better able to:
|
 | 1. Examine patient and societal concerns about opioids and addiction.
|
| 2. Explain the psychology of pleasure and pain.
|
| 3. Summarize the role of reward circuitry in addiction.
|
| 4. Describe the genetic contribution to addiction in the human population.
|
| 5. Cite the rules for treating pain with narcotics and discuss the treatment agreements and procedural
complications associated with that treatment.
|
Discussed on This Program
Acamprosate calcium [Campral]
Acetaminophen (N-acetyl-P-aminophenol; APAP) [several trade names]
Acetaminophen with codeine [Tylenol with Codeine, others]
Amitriptyline HCl [Elavil]
Cocaine [Cocaine HCl, Cocaine Viscous]
Fentanyl citrate [Sublimaze]
Fentanyl transdermal system [Duragesic-25, others]
Hydrocodone bitartrate and acetaminophen [Vicodin Tablets, others]
Hydromorphone HCl [Dilaudid, others]
Methadone HCl [several trade names]
Morphine sulfate [several trade names]
Naloxone HCl [Narcan]
Naltrexone HCl [ReVia]
Oxycodone and acetaminophen [Percocet, others] Phencyclidine HCl (PCP) [Sernylan] (withdrawn 1978)
Tamoxifen citrate [Nolvadex]
Suggested Reading
Chuck B: AANA journal course: Update for nurse anesthetists.--part 6--The long-term use of opiates for
pain control: Laputa revisited? AANA J 73:62, 2005; Elder N et al: How respected family physicians manage
difficult patient encounters. J Am Board Fam Med 19:533, 2006; Fishman SM et al: The opioid contract. Clin
J Pain 18:S70, 2002; Gardner EL: Addictive potential of cannabinoids: the underlying neurobiology. Chem
Phys Lipids 121:267, 2002; Gardner EL: What we have learned about addiction from animal models of drug
self-administration. Am J Addict 9:285, 2000; Gourlay D: Addiction and pain medicine. Pain Res Manag 10
Suppl A:38A, 2005; Kaye AD et al: Ultrarapid opiate detoxification: a review. Can J Anaesth 50:663, 2003;
Koob GF: The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction 101
Suppl 1:23, 2006; Mehta V et al: Acute pain management for opioid dependent patients. Anaesthesia 61:269,
2006; Sinatra R: The fentanyl HCl patient-controlled transdermal system (PCTS): an alternative to intravenous
patient-controlled analgesia in the postoperative setting. Clin Pharmacokinet 44 Suppl 1:1, 2005; Vukmir
RB: Drug seeking behavior. Am J Drug Alcohol Abuse 30:551, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed.
The following has been disclosed: Dr. Kreis is a member of the Speakers’ Bureaus of Pfizer and
Organon. Dr. Richeimer is a member of the Speakers’ Bureaus of Pfizer, Merck, Janssen, and Purdue
Pharma.
Drs. Kreis and Richeimer were recorded at Review and Update of Pain and Palliative Medicine, presented January
14-15, 2006, by the University of California, Davis, Health System, Division of Pain Medicine, Department of Anesthesiology
and Medicine, and Continuing Medical Education, and held in Los Angeles, CA. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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