Download Chapter 6 outline

Chapter 6:
Opioid (Narcotic) Analgesics and
Antagonists
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Chapter 6 Outline

Opioid (Narcotic) Analgesics and Antagonists

History
 Terminology
 Classification
 Mechanism of action
 Pharmacokinetics
 Pharmacologic effects
 Adverse reactions
 Specific opioids
 Dental use of opioids
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2
History
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Haveles (p. 65)
Opium is dried juice from unripe seed
capsules of the opium poppy
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As early as 4000 B.C., many cultures recognized
the euphoric effect
In the early 1800s, morphine and codeine were
isolated from opium
Until about 1920, patent medicines containing
opium were promoted; when these medicines
became unlawful, narcotic (opioid) abuse by
injection began
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Terminology
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Haveles (p. 65)
Narcotics is derived from the Greek word that
means “stupor”
Opiates refers to drugs derived from
substances in the opioid poppy
Opioids include former opiates but also other
structurally different agents, their antagonists,
and receptors simulated by opioids
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4
Classification
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They may be classified by their mechanism of
action at receptor sites: agonists, mixed
opioids, and antagonists
They may also be classified by their chemical
structure

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Haveles (pp. 66-67) (Box 6-1; Table 6-1)
Useful when the patient has a history of allergy
They may be classified by their efficacy
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5
Selected Opioid Analgesics by
Efficacy
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Strongest
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Morphine intramuscularly (IM) 10 mg
methadone (Dolophine) IM 10 mg, orally (PO) 10 mg
meperidine (Demerol) IM 100 mg, PO 50 mg
hydromorphone (Dilaudid) PO 2 mg
Intermediate
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Haveles (p. 66) (Table 6-2)
oxycodone (in Percodan, Percocet, Tylox, Roxiprin, Roxicet) PO
5 mg
pentazocine (in Talwin NX) PO 50 mg
Weakest
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hydrocodone (in Vicodin, Lortab, Lorcet) PO 5 mg
codeine (Tylenol #3, Empirin #3) PO 30 mg
dihydrocodeine (in Synalgos-DC) PO 30 mg
propoxyphene (in Darvocet-N 100) PO 65 (HCl) or 100 (N)
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6
Mechanism of Action
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Opioids bind to receptors in both the central
nervous system (CNS) and the spinal cord,
producing an altered perception of reaction to
pain

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Haveles (p. 67) (Fig. 6-1; Table 6-3)
Receptors that mediate specific pharmacologic effects
and adverse reactions are stimulated by individual
opioids
Natural opioid-like substances are in the body,
called enkephalins, endorphins, and dynorphins

Have analgesic action and addiction potential
cont’d…
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Mechanism of Action
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Haveles (p. 67) (Fig. 6-1; Table 6-3)
Opioid receptors include mu (μ), kappa (κ),
and delta (δ) receptors
Naloxone is an antagonist at the three
receptor sites
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8
Pharmacokinetics
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Haveles (pp. 66-68) (Table 6-2)
Absorption: most opioids are absorbed well
orally; absorption occurs the through lungs
and from nasal and oral mucosa
Distribution: variable first-pass metabolism in
the liver or intestinal cell wall
Metabolism: major route is conjugation with
glucuronic acid in the liver
Excretion: metabolized opioids are excreted
by glomerular filtration
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9
Pharmacologic Effects
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Haveles (p. 68) (Fig. 6-2)
In general, the severity of side effects is
proportional to the efficacy (strength)
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Analgesia: raises the pain threshold
Sedation and euphoria
Cough suppression: depresses the cough center
in the medulla (antitussive)
Gastrointestinal (GI) effects: increased smoothmuscle tone of intestinal tract to decreased
propulsive contractions and motility
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10
Adverse Reactions
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Haveles (pp. 68-70) (Table 6-4)
An extension of pharmacologic effects
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Respiratory depression: usually the cause of death with
overdose
Nausea and emesis: result of direct stimulation of
chemoreceptor trigger zone (CTZ) in the medulla
Constipation: caused by tonic contraction of the GI tract
Myosis: pinpoint pupils
Urinary retention: increased smooth muscle tone in
urinary tract
CNS effects: occasional stimulation, exhibited by
anxiety, restlessness, or nervousness
cont’d…
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Adverse Reactions
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Cardiovascular effects: may depress the
vasomotor center and stimulate the vagus nerve
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Haveles (p. 69)
With high doses, postural hypotension, bradycardia,
and syncope may result
Biliary tract constriction: in high doses, may
constrict the biliary duct
Histamine release: opioids can stimulate
release; itching and urticaria can result
Pregnancy and nursing considerations: not
teratogenic; may prolong labor or depress fetal
respiration
cont’d…
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12
Adverse Reactions
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
Haveles (pp. 69-70)
Addiction: potential is proportional to analgesic
strength, tolerance occurs to effects except
myosis and constipation
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Overdose
• Major symptom is respiratory depression
Withdrawal: symptoms include yawning, lacrimation,
perspiration, rhinorrhea, gooseflesh, irritability, nausea,
vomiting, tachycardia, tremors, and chills
Identification of addict: “shoppers”
Treatment: substituting oral form for injectable, going
“cold turkey”
• Methadone maintenance: orally effective, long-acting
antagonist
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13
Allergic Reactions
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Haveles (pp. 66, 70-71) (Fig. 6-3; Box 6-1)
Most common type of true allergic reaction
includes skin rashes and urticaria
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An opioid from a different chemical class should
be chosen
Some brands of opioid analgesic combinations are
formulated with sodium bisulfate
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14
Drug Interactions
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Haveles (pp. 70-71) (Table 6-5)
The respiratory depression produced by
opioids is additive with other CNS
depressants such as alcohol, sedativehypnotic agents, promethazine or
hydroxyzine
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All opioids can interact with monoamine oxidase
(MAO) inhibitors
May be an increased effect of meperidine with
antipsychotic agents such as chlorpromazine
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15
Specific Opioids
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Haveles (pp. 70-74)
Opioid agonists
Mixed opioids
Tramadol
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16
Opioid Agonists
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Haveles (pp. 66, 70-72) (Tables 6-2, 6-6)
Morphine: prototype; used parenterally for
postoperative pain in hospitalized patients;
used orally primarily in treatment of terminal
illnesses
Oxycodone: used alone or combined with
aspirin (in Percodan) or acetaminophen (in
Percocet, Tylox)
Hydrocodone: many combinations with
acetaminophen
cont’d…
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17
Opioid Agonists
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Haveles (pp. 71-73) (Table 6-6)
Codeine: the most commonly used opioid in
dentistry, combined with acetaminophen for
oral administration: #2 (15 mg), #3 (30 mg),
#4 (60 mg)
propoxyphene (Darvon): structurally and
chemically similar to methadone, analgesic
efficacy has been questioned
meperidine HCl (Demerol): “poor choice for
oral use”
cont’d…
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18
Opioid Agonists
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Haveles (p. 73)
hydromorphone (Dilaudid): an orally effective
opioid, reserved for management of severe pain
methadone (Dolophine): used primarily to treat
opioid addicts
fentanyl family (Duragesic, Sublimaze),
sufentanil (Sufenta), and alfentanil (Alfenta):
short-acting parenterally administered agonist
opioid analgesics used perioperatively or during
general anesthesia
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19
Mixed Opioids
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Haveles (pp. 73-74)
Agonist-antagonist opioids
Partial agonists
Opioid antagonists
cont’d…
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20
Mixed Opioids
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Include agonist-antagonist opioid analgesics
and the partial agonists
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Haveles (p. 73)
The only mixed opioid for oral use is pentazocine
butorphanol (Stadol), a nasal spray, is also in this
group
This group is ripe for research to develop
opioids with adequate analgesic potency and
fewer side effects
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21
Agonist-antagonist Opioids
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Haveles (pp. 73-74)
pentazocine (Talwin): the only agonistantagonist opioid available in oral form
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CNS effects similar to opioid agonists: analgesia,
sedation, and respiratory depression
The type of analgesia produced is somewhat
different from that produced by agonist opioids
Adverse reactions: sedation, dizziness, nausea,
vomiting, and headache
cont’d…
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22
Agonist-antagonist Opioids
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Pentazocine is available as tablets containing
50 mg of pentazocine and 0.5 mg of naloxone, a
pure opioid antagonist (Talwin-NX)
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Naloxone is effective parenterally but not orally
because it is inactivated
If the contents of the tablet are injected parenterally,
the active naloxone will counteract the action of
pentazocine
This combination tablet is more difficult to abuse
Parenterally available agonist-antagonists
include dezocine (Dalgan), nalbuphine
(Nubain), and butorphanol (Stadol)
cont’d…
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23
Agonist-antagonist Opioids
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When originally marketed, these agonistantagonists were said to have much less
addiction potential or even none at all
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Haveles (p. 74)
They were not placed on any narcotic schedule by
the Drug Enforcement Administration
Current literature and clinical practice has
determined that they do have addiction
potential
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24
Partial Agonists
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Haveles (p. 74)
The first and only available partial agonist is
buprenorphine (Buprenex, Subutex)
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In abstinent morphine-dependent patients, it
suppresses withdrawal
In stabilized opioid-dependent patients, it
precipitates withdrawal
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25
Opioid Antagonists
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Haveles (p. 74)
naloxone (Narcan): pure opioid antagonist; active
parenterally
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The drug of choice for treating agonist or mixed opioid
overdoses
 It will reverse opioid-induced respiratory depression
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nalmefene (Revex): another parenteral opioid
antagonist
naltrexone (Trexan): a long-acting, orally effective
opioid antagonist
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Indicated for maintenance of the opioid free state in
detoxified, formerly opioid-dependent patients
Also used in management of alcohol abstinence
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26
tramadol (Ultram)
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Haveles (p. 74) (Table 6-7)
A new, unique analgesic
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Has μ: opioid agonist action and inhibits reuptake
of norepinephrine and serotonin
Adverse reactions include CNS effects such as
dizziness, somnolence, headache, and stimulation
GI tract side effects include nausea, diarrhea,
constipation, and vomiting
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27
Dental Use of Opioids
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The advent of nonsteroidal antiinflammatory drugs
(NSAIDs) has changed the used of opioids in
dental practice
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Haveles (pp. 74-75) (Box 6-2)
Most dental pain is better managed with use of NSAIDs;
in the patient in whom NSAIDs are contraindicated, the
dentist has a wide variety of opioids from which to
choose
Opioids are only used in rare cases for short periods
Opioids are not indicated for chronic pain
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28