chapter 6: opioid (narcotic) analgesics and antagonists copyright © 2011, 2007 mosby, inc., an...

Chapter 6:Chapter 6:

Opioid (Narcotic) Analgesics and Opioid (Narcotic) Analgesics and AntagonistsAntagonists

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 6 OutlineChapter 6 Outline

Opioid (Narcotic) Analgesics and Antagonists Opioid (Narcotic) Analgesics and Antagonists HistoryHistory TerminologyTerminology ClassificationClassification Mechanism of actionMechanism of action PharmacokineticsPharmacokinetics Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Specific opioidsSpecific opioids Dental use of opioidsDental use of opioids


HistoryHistory

Haveles (p. 65)Haveles (p. 65) Opium is dried juice from unripe seed Opium is dried juice from unripe seed

capsules of the opium poppycapsules of the opium poppy As early as 4000 B.C., many cultures recognized As early as 4000 B.C., many cultures recognized

the euphoric effectthe euphoric effect In the early 1800s, morphine and codeine were In the early 1800s, morphine and codeine were

isolated from opiumisolated from opium Until about 1920, patent medicines containing Until about 1920, patent medicines containing

opium were promoted; when these medicines opium were promoted; when these medicines became unlawful, narcotic (opioid) abuse by became unlawful, narcotic (opioid) abuse by injection beganinjection began


TerminologyTerminology

Haveles (p. 65)Haveles (p. 65) Narcotics Narcotics is derived from the Greek word that is derived from the Greek word that

means “stupor”means “stupor” Opiates Opiates refers to drugs derived from refers to drugs derived from

substances in the opioid poppysubstances in the opioid poppy OpioidsOpioids include former opiates but also other include former opiates but also other

structurally different agents, their antagonists, structurally different agents, their antagonists, and receptors simulated by opioidsand receptors simulated by opioids


ClassificationClassification

Haveles (pp. 66-67) (Box 6-1; Table 6-1)Haveles (pp. 66-67) (Box 6-1; Table 6-1) They may be classified by their mechanism of They may be classified by their mechanism of

action at receptor sites: agonists, mixed action at receptor sites: agonists, mixed opioids, and antagonists opioids, and antagonists

They may also be classified by their chemical They may also be classified by their chemical structurestructure Useful when the patient has a history of allergyUseful when the patient has a history of allergy

They may be classified by their efficacyThey may be classified by their efficacy


Selected Opioid Analgesics by Selected Opioid Analgesics by EfficacyEfficacy

Haveles (p. 66) (Table 6-2) Haveles (p. 66) (Table 6-2) StrongestStrongest

Morphine intramuscularly (IM) 10 mgMorphine intramuscularly (IM) 10 mg methadone (Dolophine) IM 10 mg, orally (PO) 10 mgmethadone (Dolophine) IM 10 mg, orally (PO) 10 mg meperidine (Demerol) IM 100 mg, PO 50 mgmeperidine (Demerol) IM 100 mg, PO 50 mg hydromorphone (Dilaudid) PO 2 mghydromorphone (Dilaudid) PO 2 mg

IntermediateIntermediate oxycodone (in Percodan, Percocet, Tylox, Roxiprin, Roxicet) PO oxycodone (in Percodan, Percocet, Tylox, Roxiprin, Roxicet) PO

5 mg5 mg pentazocine (in Talwin NX) PO 50 mgpentazocine (in Talwin NX) PO 50 mg

WeakestWeakest hydrocodone (in Vicodin, Lortab, Lorcet) PO 5 mghydrocodone (in Vicodin, Lortab, Lorcet) PO 5 mg codeine (Tylenol #3, Empirin #3) PO 30 mgcodeine (Tylenol #3, Empirin #3) PO 30 mg dihydrocodeine (in Synalgos-DC) PO 30 mgdihydrocodeine (in Synalgos-DC) PO 30 mg propoxyphene (in Darvocet-N 100) PO 65 (HCl) or 100 (N) propoxyphene (in Darvocet-N 100) PO 65 (HCl) or 100 (N)


Mechanism of ActionMechanism of Action Haveles (p. 67) (Fig. 6-1; Table 6-3)Haveles (p. 67) (Fig. 6-1; Table 6-3)

Opioids bind to receptors in both the central Opioids bind to receptors in both the central nervous system (CNS) and the spinal cord, nervous system (CNS) and the spinal cord, producing an altered perception of reaction to producing an altered perception of reaction to painpain Receptors that mediate specific pharmacologic effects Receptors that mediate specific pharmacologic effects

and adverse reactions are stimulated by individual and adverse reactions are stimulated by individual opioidsopioids

Natural opioid-like substances are in the body, Natural opioid-like substances are in the body, called enkephalins, endorphins, and dynorphins called enkephalins, endorphins, and dynorphins Have analgesic action and addiction potentialHave analgesic action and addiction potential

cont’d…cont’d…


Mechanism of ActionMechanism of Action

Haveles (p. 67) (Fig. 6-1; Table 6-3) Haveles (p. 67) (Fig. 6-1; Table 6-3) Opioid receptors include mu (Opioid receptors include mu (μμ)), kappa (, kappa (κκ)), ,

and delta (and delta (δδ)) receptors receptors Naloxone is an antagonist at the three Naloxone is an antagonist at the three

receptor sitesreceptor sites


PharmacokineticsPharmacokinetics

Haveles (pp. 66-68) (Table 6-2)Haveles (pp. 66-68) (Table 6-2) Absorption: most opioids are absorbed well Absorption: most opioids are absorbed well

orally; absorption occurs the through lungs orally; absorption occurs the through lungs and from nasal and oral mucosaand from nasal and oral mucosa

Distribution: variable first-pass metabolism in Distribution: variable first-pass metabolism in the liver or intestinal cell wallthe liver or intestinal cell wall

Metabolism: major route is conjugation with Metabolism: major route is conjugation with glucuronic acid in the liverglucuronic acid in the liver

Excretion: metabolized opioids are excreted Excretion: metabolized opioids are excreted by glomerular filtration by glomerular filtration


Pharmacologic EffectsPharmacologic Effects

Haveles (p. 68) (Fig. 6-2)Haveles (p. 68) (Fig. 6-2) In general, the severity of side effects is In general, the severity of side effects is

proportional to the efficacy (strength) proportional to the efficacy (strength) Analgesia: raises the pain threshold Analgesia: raises the pain threshold Sedation and euphoriaSedation and euphoria Cough suppression: depresses the cough center Cough suppression: depresses the cough center

in the medulla (antitussive)in the medulla (antitussive) Gastrointestinal (GI) effects: increased smooth-Gastrointestinal (GI) effects: increased smooth-

muscle tone of intestinal tract to decreased muscle tone of intestinal tract to decreased propulsive contractions and motilitypropulsive contractions and motility


Adverse Reactions Adverse Reactions Haveles (pp. 68-70) (Table 6-4)Haveles (pp. 68-70) (Table 6-4)

An extension of pharmacologic effectsAn extension of pharmacologic effects Respiratory depression: usually the cause of death with Respiratory depression: usually the cause of death with

overdoseoverdose Nausea and emesis: result of direct stimulation of Nausea and emesis: result of direct stimulation of

chemoreceptor trigger zone (CTZ) in the medullachemoreceptor trigger zone (CTZ) in the medulla Constipation: caused by tonic contraction of the GI tractConstipation: caused by tonic contraction of the GI tract Myosis: pinpoint pupilsMyosis: pinpoint pupils Urinary retention: increased smooth muscle tone in urinary Urinary retention: increased smooth muscle tone in urinary

tracttract CNS effects: occasional stimulation, exhibited by anxiety, CNS effects: occasional stimulation, exhibited by anxiety,

restlessness, or nervousnessrestlessness, or nervousnesscont’d…cont’d…


Adverse Reactions Adverse Reactions Haveles (p. 69)Haveles (p. 69)

Cardiovascular effects: may depress the Cardiovascular effects: may depress the vasomotor center and stimulate the vagus nervevasomotor center and stimulate the vagus nerve With high doses, postural hypotension, bradycardia, With high doses, postural hypotension, bradycardia,

and syncope may resultand syncope may result Biliary tract constriction: in high doses, may Biliary tract constriction: in high doses, may

constrict the biliary ductconstrict the biliary duct Histamine release: opioids can stimulate Histamine release: opioids can stimulate

release; itching and urticaria can resultrelease; itching and urticaria can result Pregnancy and nursing considerations: not Pregnancy and nursing considerations: not

teratogenic; may prolong labor or depress fetal teratogenic; may prolong labor or depress fetal respirationrespiration



Adverse ReactionsAdverse Reactions Haveles (pp. 69-70)Haveles (pp. 69-70)

Addiction: potential is proportional to analgesic Addiction: potential is proportional to analgesic strength, tolerance occurs to effects except myosis strength, tolerance occurs to effects except myosis and constipationand constipation Overdose Overdose

• Major symptom is respiratory depressionMajor symptom is respiratory depression Withdrawal: symptoms include yawning, lacrimation, Withdrawal: symptoms include yawning, lacrimation,

perspiration, rhinorrhea, gooseflesh, irritability, nausea, perspiration, rhinorrhea, gooseflesh, irritability, nausea, vomiting, tachycardia, tremors, and chills vomiting, tachycardia, tremors, and chills

Identification of addict: “shoppers”Identification of addict: “shoppers” Treatment: substituting oral form for injectable, going “cold Treatment: substituting oral form for injectable, going “cold

turkey”turkey”• Methadone maintenance:Methadone maintenance: orally effective, long-acting antagonist orally effective, long-acting antagonist


Allergic ReactionsAllergic Reactions

Haveles (pp. 66, 70-71) (Fig. 6-3; Box 6-1)Haveles (pp. 66, 70-71) (Fig. 6-3; Box 6-1) Most common type of true allergic reaction Most common type of true allergic reaction

includes skin rashes and urticariaincludes skin rashes and urticaria An opioid from a different chemical class should An opioid from a different chemical class should

be chosenbe chosen Some brands of opioid analgesic combinations are Some brands of opioid analgesic combinations are

formulated with sodium bisulfateformulated with sodium bisulfate


Drug InteractionsDrug Interactions

Haveles (pp. 70-71) (Table 6-5)Haveles (pp. 70-71) (Table 6-5) The respiratory depression produced by The respiratory depression produced by

opioids is additive with other CNS opioids is additive with other CNS depressants such as alcohol, sedative-depressants such as alcohol, sedative-hypnotic agents, promethazine or hypnotic agents, promethazine or hydroxyzinehydroxyzine All opioids can interact with monoamine oxidase All opioids can interact with monoamine oxidase

(MAO) inhibitors(MAO) inhibitors May be an increased effect of meperidine with May be an increased effect of meperidine with

antipsychotic agents such as chlorpromazineantipsychotic agents such as chlorpromazine


Specific OpioidsSpecific Opioids

Haveles (pp. 70-74)Haveles (pp. 70-74) Opioid agonistsOpioid agonists Mixed opioidsMixed opioids TramadolTramadol


Opioid AgonistsOpioid Agonists

Haveles (pp. 66, 70-72) (Tables 6-2, 6-6)Haveles (pp. 66, 70-72) (Tables 6-2, 6-6) Morphine: prototype; used parenterally for Morphine: prototype; used parenterally for

postoperative pain in hospitalized patients; used postoperative pain in hospitalized patients; used orally primarily in treatment of terminal illnesses orally primarily in treatment of terminal illnesses

Oxycodone: used alone or combined with Oxycodone: used alone or combined with aspirin (in Percodan) or acetaminophen (in aspirin (in Percodan) or acetaminophen (in Percocet, Tylox)Percocet, Tylox)

Hydrocodone: many combinations with Hydrocodone: many combinations with acetaminophenacetaminophen




Haveles (pp. 71-73) (Table 6-6)Haveles (pp. 71-73) (Table 6-6) Codeine: the most commonly used opioid in Codeine: the most commonly used opioid in

dentistry, combined with acetaminophen for dentistry, combined with acetaminophen for oral administration: #2 (15 mg), #3 (30 mg), oral administration: #2 (15 mg), #3 (30 mg), #4 (60 mg)#4 (60 mg)

propoxyphene (Darvon): structurally and propoxyphene (Darvon): structurally and chemically similar to methadone, analgesic chemically similar to methadone, analgesic efficacy has been questionedefficacy has been questioned

meperidine HCl (Demerol): “poor choice for meperidine HCl (Demerol): “poor choice for oral use”oral use”




Haveles (p. 73)Haveles (p. 73) hydromorphone (Dilaudid): an orally effective hydromorphone (Dilaudid): an orally effective

opioid, reserved for management of severe painopioid, reserved for management of severe pain methadone (Dolophine): used primarily to treat methadone (Dolophine): used primarily to treat

opioid addictsopioid addicts fentanyl family (Duragesic, Sublimaze), fentanyl family (Duragesic, Sublimaze),

sufentanil (Sufenta), and alfentanil (Alfenta): sufentanil (Sufenta), and alfentanil (Alfenta): short-acting parenterally administered agonist short-acting parenterally administered agonist opioid analgesics used perioperatively or during opioid analgesics used perioperatively or during general anesthesiageneral anesthesia


Mixed OpioidsMixed Opioids

Haveles (pp. 73-74)Haveles (pp. 73-74) Agonist-antagonist opioidsAgonist-antagonist opioids Partial agonistsPartial agonists Opioid antagonistsOpioid antagonists



Mixed OpioidsMixed Opioids

Haveles (p. 73)Haveles (p. 73) Include agonist-antagonist opioid analgesics Include agonist-antagonist opioid analgesics

and the partial agonistsand the partial agonists The only mixed opioid for oral use is pentazocineThe only mixed opioid for oral use is pentazocine butorphanol (Stadol), a nasal spray, is also in this butorphanol (Stadol), a nasal spray, is also in this

groupgroup This group is ripe for research to develop This group is ripe for research to develop

opioids with adequate analgesic potency and opioids with adequate analgesic potency and fewer side effects fewer side effects


Agonist-antagonist OpioidsAgonist-antagonist Opioids

Haveles (pp. 73-74)Haveles (pp. 73-74) pentazocine (Talwin): the only agonist-pentazocine (Talwin): the only agonist-

antagonist opioid available in oral formantagonist opioid available in oral form CNS effects similar to opioid agonists: analgesia, CNS effects similar to opioid agonists: analgesia,

sedation, and respiratory depressionsedation, and respiratory depression The type of analgesia produced is somewhat The type of analgesia produced is somewhat

different from that produced by agonist opioidsdifferent from that produced by agonist opioids Adverse reactions: sedation, dizziness, nausea, Adverse reactions: sedation, dizziness, nausea,

vomiting, and headachevomiting, and headache



Agonist-antagonist OpioidsAgonist-antagonist Opioids Pentazocine is available as tablets containing Pentazocine is available as tablets containing

50 mg of pentazocine and 0.5 mg of naloxone, a 50 mg of pentazocine and 0.5 mg of naloxone, a pure opioid antagonist (Talwin-NX)pure opioid antagonist (Talwin-NX) Naloxone is effective parenterally but not orally Naloxone is effective parenterally but not orally

because it is inactivatedbecause it is inactivated If the contents of the tablet are injected parenterally, If the contents of the tablet are injected parenterally,

the active naloxone will counteract the action of the active naloxone will counteract the action of pentazocinepentazocine

This combination tablet is more difficult to abuseThis combination tablet is more difficult to abuse Parenterally available agonist-antagonists Parenterally available agonist-antagonists

include dezocine (Dalgan), nalbuphine (Nubain), include dezocine (Dalgan), nalbuphine (Nubain), and butorphanol (Stadol)and butorphanol (Stadol)



Agonist-antagonist OpioidsAgonist-antagonist Opioids

Haveles (p. 74)Haveles (p. 74) When originally marketed, these agonist-When originally marketed, these agonist-

antagonists were said to have much less antagonists were said to have much less addiction potential or even none at alladdiction potential or even none at all They were not placed on any narcotic schedule by They were not placed on any narcotic schedule by

the Drug Enforcement Administrationthe Drug Enforcement Administration Current literature and clinical practice has Current literature and clinical practice has

determined that they do have addiction determined that they do have addiction potentialpotential


Partial Agonists Partial Agonists

Haveles (p. 74)Haveles (p. 74) The first and only available partial agonist is The first and only available partial agonist is

buprenorphine (Buprenex, Subutex)buprenorphine (Buprenex, Subutex) In abstinent morphine-dependent patients, it In abstinent morphine-dependent patients, it

suppresses withdrawalsuppresses withdrawal In stabilized opioid-dependent patients, it In stabilized opioid-dependent patients, it

precipitates withdrawalprecipitates withdrawal


Opioid AntagonistsOpioid Antagonists Haveles (p. 74)Haveles (p. 74)

naloxone (Narcan): pure opioid antagonist; active naloxone (Narcan): pure opioid antagonist; active parenterallyparenterally The drug of choice for treating agonist or mixed opioid The drug of choice for treating agonist or mixed opioid

overdosesoverdoses It will reverse opioid-induced respiratory depression It will reverse opioid-induced respiratory depression

nalmefene (Revex): another parenteral opioid antagonistnalmefene (Revex): another parenteral opioid antagonist naltrexone (Trexan): a long-acting, orally effective opioid naltrexone (Trexan): a long-acting, orally effective opioid

antagonistantagonist Indicated for maintenance of the opioid free state in detoxified, Indicated for maintenance of the opioid free state in detoxified,

formerly opioid-dependent patientsformerly opioid-dependent patients Also used in management of alcohol abstinenceAlso used in management of alcohol abstinence


tramadol (Ultram)tramadol (Ultram)

Haveles (p. 74) (Table 6-7)Haveles (p. 74) (Table 6-7) A new, unique analgesicA new, unique analgesic

Has Has μμ: opioid agonist action and inhibits reuptake : opioid agonist action and inhibits reuptake of norepinephrine and serotoninof norepinephrine and serotonin

Adverse reactions include CNS effects such as Adverse reactions include CNS effects such as dizziness, somnolence, headache, and stimulationdizziness, somnolence, headache, and stimulation

GI tract side effects include nausea, diarrhea, GI tract side effects include nausea, diarrhea, constipation, and vomitingconstipation, and vomiting


Dental Use of OpioidsDental Use of Opioids Haveles (pp. 74-75) (Box 6-2)Haveles (pp. 74-75) (Box 6-2)

The advent of The advent of nonsteroidal antiinflammatory drugs nonsteroidal antiinflammatory drugs ((NSAIDs) has changed the used of opioids in NSAIDs) has changed the used of opioids in dental practicedental practice Most dental pain is better managed with use of NSAIDs; Most dental pain is better managed with use of NSAIDs;

in the patient in whom NSAIDs are contraindicated, the in the patient in whom NSAIDs are contraindicated, the dentist has a wide variety of opioids from which to dentist has a wide variety of opioids from which to choosechoose

Opioids are only used in rare cases for short periodsOpioids are only used in rare cases for short periods Opioids are not indicated for chronic painOpioids are not indicated for chronic pain

chapter 6: opioid (narcotic) analgesics and antagonists copyright © 2011, 2007 mosby, inc., an...

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