Chapter 24: Opioid Analgesics, Opioid Antagonist, and Nonopioid Centrally Acting Analgesics

Question 1

analgesics and opioids

Answer 1

Analgesics are drugs that relieve pain without causing the loss of consciousness​

Opioids are the most effective pain relievers available​

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Question 2

opioid

Answer 2

A general term that is defined as any drug, natural or synthetic, that has actions similar to those of morphine

Question 3

opiate

Answer 3

A term that applies only to compounds present in opium

Question 4

endogenous opioid peptides

Answer 4

Three families of peptides​:

Enkephalins​

Endorphins​

Dynorphins​

Question 5

opioid receptors

Answer 5

Three main classes of opioid receptors​

Mu receptors: Analgesia, respiratory depression, euphoria, sedation, and physical dependence​

Kappa receptors: Analgesia and sedation; kappa activation may underlie psychotomimetic effects seen with certain opioids​

Delta receptors​

Question 6

Classification of Drugs That ​
Act as Opioid Receptors​

Answer 6

Agonist, partial agonist, or antagonist​:

Pure opioid agonists​

Agonist-antagonist opioids​

Pure opioid antagonists

Question 7

Pure Opioid Agonists​

Answer 7

Activate mu receptors and kappa receptors​

Can produce analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation, and other effects​

2 groups: strong and mod-to-strong agonist:

Morphine: Strong opioid agonists and moderate to strong opioid agonists​

Codeine: Moderate to strong agonists

Question 8

Agonist-Antagonist Opioids​

Answer 8

Pentazocine, nalbuphine, butorphanol, and buprenorphine​

When administered alone, produce analgesia​

If administered with a pure opioid agonist, can antagonize analgesia caused by the pure agonist

Question 9

Pure Opioid Antagonists​

Answer 9

Naloxone [Narcan]: Prototype of the pure opioid antagonists​

Antagonists at mu and kappa receptors​

Do not produce analgesia or any of the other effects caused by opioid agonists​

Reversal of respiratory and central nervous system (CNS) depression caused by overdose with opioid agonists​

Methylnaltrexone: Used to treat opioid-induced constipation​

Question 10

basic pharm of the opioids

Answer 10

Strong opioid agonists​:
Morphine​
Other strong opioid agonists​

Moderate to strong opioid agonists​

Agonist-antagonist opioids​

Question 11

source of morphine

Answer 11

Seedpod of the poppy plant​

Question 12

morphine: overview of pharm actions

Answer 12

Pain relief​

Drowsiness​

Mental clouding​

Anxiety reduction​

Sense of well-being

Respiratory depression​

Constipation​

Urinary retention​

Orthostatic hypotension​

Emesis​

Miosis​

Cough suppression​

Biliary colic​

Tolerance and physical dependence​​

Question 13

morphine therapeutic use

Answer 13

Relief of pain​ -mod to severe. post-op pain, L&D pain, chronic pain caused by cancer and other conditions.

more effective against constant, dull pain than against sharp, intermittent pain. however, sharp pain can be relieved by large doses

Relieves pain without affecting other senses (e.g., sight, touch, smell, and hearing)​

No loss of consciousness​

Relieves pain by mimicking the actions of endogenous opioid peptides, primarily at mu receptors​

sched 2

Question 14

morphine ADR: resp depression

Answer 14

Infants and the elderly are especially sensitive​

Onset: ​
Intravenous, 7 minutes; intramuscular, 30 minutes; subcutaneous, up to 90 minutes; may persist 4 to 5 hours​
Spinal injection: Response may be delayed by hours​
PO: 90 min

Tolerance to respiratory depression can develop​

Increased depression with concurrent use of other drugs that have CNS depressant actions (e.g., alcohol, barbiturates, and benzodiazepines) ​

Can compromise patients with impaired pulmonary function ​

Asthma, emphysema, kyphoscoliosis, chronic cor pulmonale, and extreme obesity​

Question 15

morphine ADR: constipation

Answer 15

Cause: Suppressed propulsive intestinal contractions, intensified nonpropulsive contractions, increased tone of the anal sphincter, and inhibited secretion of fluids into the intestinal lumen​

Complications of constipation include fecal impaction, bowel perforation, rectal tearing, and hemorrhoids​

Treatment includes physical activity, increased intake of fiber and fluids, stimulant laxatives, stool softeners, and polyethylene glycol

last resort: methylnaltrexone -cant cross BBB so won’t reverse pain relief

Question 16

morphine ADR: ortho hypotension

Answer 16

Morphine-like drugs lower blood pressure by blunting the baroreceptor reflex and by dilating peripheral arterioles and veins​

Patient teaching: Symptoms of hypotension (e.g., lightheadedness and dizziness) and instructions to sit or lie down if they occur​

Hypotension can be minimized by moving slowly when changing from a supine or seated position to an upright position​

hypotensive medications can exacerbate opioid induced hypotension

Question 17

morphine ADR: urinary retention and hesitancy

Answer 17

Increases tone in the bladder sphincter​

Increases tone in the detrusor muscle, thereby elevating pressure within the bladder and causing a sense of urinary urgency​

May interfere with voiding by suppressing awareness of bladder stimuli​

encourage pt to void every 4 hr

likely in pt with BPH. anticholinergic meds can exacerbate

Question 18

morphine ADR: emesis

Answer 18

Promotes nausea and vomiting through the direct stimulation of the chemoreceptor trigger zone of the medulla​

Emetic reactions are greatest with the initial dose and then diminish with subsequent doses​

Nausea and vomiting are uncommon in recumbent patients but occur in 15% to 40% of ambulatory patients​

Nausea and vomiting can be reduced by pretreatment with an antiemetic (e.g., prochlorperazine) and by having the patient remain still

Question 19

morphine ADR: euphoria/dysphoria

Answer 19

Euphoria: An exaggerated sense of well-being caused by the activation of mu receptors​

Dysphoria: A sense of anxiety and unease​

Dysphoria is uncommon among patients in pain, but it may occur when morphine is taken in the absence of pain​

Question 20

morphine ADR: sedation

Answer 20

Drowsiness and some mental clouding​

Avoid hazardous activities​

Sedation can be minimized:​
Take smaller doses more often ​
Use opioids that have short half-lives​
Give small doses of a CNS stimulant (e.g., methylphenidate or dextroamphetamine)​
Nonamphetamine stimulants such as modafinil [Provigil, Alertec] or armodafinil [Nuvigil] may also be tried​

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Question 21

morphine ADR: neurotoxicity

Answer 21

Delirium, agitation, myoclonus, hyperalgesia, and other symptoms​

Risk factors include renal impairment, preexisting cognitive impairment, and prolonged high-dose opioid use​

Management: Hydration and dose reduction​, opioid rotation for long term user is helpful

Question 22

morphine ADR: tolerance

Answer 22

Tolerance​

Increased doses needed to obtain the same response​

Develops with analgesia, euphoria, sedation, and respiratory depression​

Cross-tolerance to other opioid agonists​

No tolerance to miosis or constipation develops

Question 23

morphine ADR: physical dependence

Answer 23

Abstinence syndrome with abrupt discontinuation​

About 10 hours after last dose, the initial reaction occurs and includes yawning, rhinorrhea, and sweating​

Progresses to violent sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasms, and kicking movements​

Lasts 7 to 10 days if untreated​

Withdrawal is unpleasant but not lethal, as it may be with CNS depressants

Question 24

morphine pharmakinetics

Answer 24

Administered by several routes: oral, intramuscular, intravenous, subcutaneous, epidural, and intrathecal​

Not very lipid-soluble​

Does not cross blood-brain barrier easily​

Only small fraction of each dose reaches site of analgesic action​

Question 25

morphine precautions

Answer 25

Abuse liability​ Use cautiously in pt with: Decreased respiratory reserve​ Pregnancy​ Labor and delivery​ Head injury​ Other precautions

Question 26

morphine drug interactions

Answer 26

CNS depressants​ Anticholinergic drugs​ Hypotensive drugs​ Monoamine oxidase inhibitors​ Agonist-antagonist opioids​ Opioid antagonists​ Other interactions​

Question 27

morphine toxicity s/sx

Answer 27

Classic triad​: Coma​ Respiratory depression​ -may be as low as 2-4 breath/min Pinpoint pupils -can dilate secondary to resp depression

Question 28

morphine tox tx

Answer 28

Ventilatory support​ Antagonist: Naloxone [Narcan]

Question 29

morphine admin general guidelines

Answer 29

Monitor vital signs before giving​ Give on a fixed schedule​

Question 30

morphine: general guidelines for dosage and admin

Answer 30

​ Morphine/naltrexone [Embeda]: Designed to discourage morphine abuse​ Dosage and routes of administration​ Oral​ Intramuscular and subcutaneous​ Intravenous​ Epidural and intrathecal​ Extended-release liposomal formulation [DepoDur]​

Question 31

fentanyl [Duragesic, Abstral, Actiq, Fentora, Onsolis, Lazanda, Subsys]

Answer 31

100 times the potency of morphine​ Formulations given via three routes​: Parenteral ​ Surgical anesthesia Transdermal [Duragesic]​ -Patch: Heat acceleration​, Iontophoretic system: Needle-free Transmucosal​ Lozenge on a stick [Actiq]​ Buccal film [Onsolis]​ Buccal tablets [Fentora]​ Sublingual tablets [Abstral]​ Sublingual spray [Subsys]​ sched 2

Question 32

codeine: actions and uses

Answer 32

10% converts to morphine in liver​ Pain (mild to mod) and cough suppression​ (sch 5) Preparations, dosage, and administration​ Usually oral (formulated alone or with aspirin or acetaminophen)​ 30 mg produces same effect as 325 mg of acetaminophen​ metabolized by p450 system in liver tox to breast fed infants whose mothers take codeine sched 2 combo sched 3

Question 33

oxycodone

Answer 33

Analgesic actions equivalent to those of codeine​ Long-acting analgesics​: Immediate-release ​ Controlled-release [OxyContin]​ Abuse: Crushes and snorts or injects medication​ 2010 OP formulation much harder to crush and does not dissolve into an injectable solution to decrease risk of abuse​ high risk for abuse sched 2

Question 34

hydrocodone

Answer 34

Most widely prescribed drug in the United States​ pain relief and cough suppressant Combined with aspirin, acetaminophen, or ibuprofen​ sched 2

Question 35

tapentadol

Answer 35

Analgesic effects equivalent to oxycodone​n (mod to severe pain) Causes less constipation than traditional medications​ blocks reuptake of NE high abuse potential sched 2

Question 36

Pentazocine

Answer 36

agonist (K receptors) -antagonist (mu receptors) opioid mild - mod pain less effective than morphine resp depression is limited, produces little to none euphoria low potential for abuse sched 2-5 depending on state if admin to a pt physically dependent on pure agonist, will withdrawal physically dependence can occur reversed with naloxone

Question 37

nalbuphinal

Answer 37

opioid agonist-antagonist IM, IV, SQ

Question 38

Buprenorphine

Answer 38

IM, IV agonist (mu) antagonist (k) if admin to a pt physically dependent on pure agonist, will withdrawal prolongs QT sched III 7-day patch: Butrans​ Sublingual film: Suboxone

Question 39

Butorphanol

Answer 39

agonist antagonist nasal spray

Question 40

pain assessment

Answer 40

Pain assessment​ Essential component of management​ Based on patient’s description​ Evaluate:​ Pain location, characteristics, and duration​ Things that improve or worsen pain​ Status before taking drug and 1 hour after​

Question 41

dosing guideline

Answer 41

Assessment of pain​ Pain status should be evaluated before opioid administration and about 1 hour after​ Dosage determination​ Opioid analgesics must be adjusted to accommodate individual variation​ start lowest dose Using a standard 10 mg dose of morph only 70% of adults will have pain relief  older adults metabolize slowly and need lower doses newborns need smaller dose dt immature BBB Dosing schedule​ As a rule, opioids should be administered on a fixed schedule​ want lowest effective dose for shortest time possible as pain diminishes, switch to nonopioid analgesic (asa, tyl) Avoiding withdrawal​ when opioids are admin in high doses for 20 days or more, physical dependence may develop. under these conditions abstinence syndrome will develop, to min opioid to be withdrawn slowly by tapering the dose over 3 days. if the degree of dependence is high, withdrawn over 7-10 days. ​

Question 42

physical dependence

Answer 42

State in which an abstinence syndrome will occur if the dependence-producing drug is abruptly withdrawn; it is NOT equated with addiction​ Withdrawal drug over longer period of time

Question 43

abuse

Answer 43

Drug use that is inconsistent with medical or social norms before prescribing, identify at risk abuse pt using NIDA-modified ASSISR. next become familiar with state prescription drug monitoring program (see all drugs prescribed to pt, who prescribed and how much). check this at initiation of tx and periodically thruout. before starting therapy, get a urine drug test. in ohio, every script requires DEA number and to be registered with DEA in order to scribe sch 2 and above. OAARs -run pt thru before writing script

Question 44

addiction

Answer 44

Behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm​

Question 45

pt education for opioids

Answer 45

Balance the need to provide pain relief with the desire to minimize abuse​ Minimize fears about the following:​ Physical dependence​ Addiction​

Question 46

prescribing guidelines for opioids

Answer 46

use opioids only after nonopioids fail discuss benefits and risks of long term opioid tx use only 1 prescriber and 1 pharm ensure comp follow up to assess efficacy and SE and monitor for abuse stop opioids after an attempt at opioid rotation has produced inadequate benefit fully document the entire process

Question 47

PCA

Answer 47

Patient-controlled analgesia devices​ Drug selection and dosage regulations​ exist -monitor Comparison of patient-controlled analgesia with traditional intramuscular therapy​ -pt feel more in control with PCA Multiple intramuscular injections: Painful to the patient; cause negative side effects, including bruising and hematoma formation​ Patient education​ and Family education​ are a good thing

Question 48

Using opioids in specific settings​

Answer 48

Postoperative pain​ Obstetric analgesia​ Myocardial infarction​ Head injury​ Cancer-related pain​ Chronic noncancer pain

Question 49

REMs

Answer 49

Risk evaluation and mitigation strategy (REMS)​ Developed by the U.S. Food and Drug Administration​ Designed to reduce opioid-related injuries and deaths​ central component to edu prescriber and pt -edu all providing care for pt in pain

Question 50

principal uses for opioid antagonists

Answer 50

Treatment of opioid overdose and relief of opioid-induced constipation​ Reversal of postoperative opioid effects​ Reversal of neonatal respiratory depression​ Management of opioid addiction​

Question 51

naloxone therapeutic uses

Answer 51

Reversal of opioid overdose​ Drug of choice with pure opioid agonist overdose​ Titrated cautiously with physical dependence​ Reversal of postoperative opioid effects​ Titrated to achieve adequate ventilation and to maintain pain relief ​ Reversal of neonatal respiratory depression​ Opioids given during labor and delivery may cause respiratory depression in neonate​

Question 52

naloxone prep and admin

Answer 52

IM or SQ onset 2-5 min duration several hours half-life 2 hr (may need repeat doses) cant be given orally dt first pass careful titration to prevent abrupt withdrawal may need higher doses to reverse agonist-antagonist tox

Question 53

Methylnaltrexone

Answer 53

Selective opioid antagonist​ Treatment of opioid-induced constipation in late-stage disease for patients receiving constant opioids​ Block mu opioid receptors in the gastrointestinal tract​

Question 54

Alvimopan

Answer 54

Peripherally acting mu opioid antagonist developed​ Counteracts the adverse effects of opioids on bowel function​ Does not reduce opioid-mediated analgesia: Limited ability to cross the blood-brain barrier​ Short-term therapy of opioid-induced ileus after partial small or large bowel resection with primary anastomosis​

Question 55

naltrexone

Answer 55

Pure opioid antagonist​ Opioid and alcohol abuse​ Opioid abuse: Prevents euphoria if the abuser takes an opioid​ Candidates for treatment must be rendered opioid free before naltrexone is started​ Does not prevent craving for opioids​ PO or IM can cause hepatocellular injury with excessive dosage, contraindicated for hepatitis pt, educate pt on r/o liver injury and signs of hepatitis less effective than methdone (suppresses cravings and euphoria)

Question 56

nonopioid centrally acting analgesics

Answer 56

Relieve pain by mechanisms largely or completely unrelated to opioid receptors​ Do not cause respiratory depression, physical dependence, or abuse​ Not regulated under the Controlled Substances Act​ Tramadol [Ultram]​ Suicide risk​ Clonidine [Duraclon]​ Ziconotide [Prialt]​ Dexmedetomidine [Precedex]​

Question 57

tramadol MOA

Answer 57

weak agonist activity at mu receptors. block uptake of NE and serotonin, thereby activating monoaminergic spinal inhibition of pain. BC of this, naloxone only partially blocks effects

Question 58

tramaol therapeutic uses

Answer 58

mod- mod severe pain less effective than morphine, more effective then codeine combo

Question 59

tramadol ADRs

Answer 59

resp depression min sedation, dizziness, HA, dry mouth, constipation sz

Question 60

tramadol drug interactions

Answer 60

intensify responses to CNS depressants (alc, benzo) hypertensive crisis with MAOI serotonin syndrome with SSRI, SNRI, TCA, MAOIs

Question 61

abuse liability of tramadol

Answer 61

very low sched 4

Question 62

tramadol prep, dosage, and admin

Answer 62

PO IM onset 1 hr, peak 2 hr, duration 6 hr. half life 5-6 hr PO ER

Question 63

clonidine

Answer 63

Treatment of hypertension and relief of severe pain​ Mechanism of pain relief​ Alpha2-adrenergic agonist​ Analgesic use​ Used in combination with opioid analgesics​ Adverse effects​ Cardiovascular: Severe hypotension, rebound hypertension, and bradycardia​ Contraindication: hypot​ension ​

Question 64

Ziconotide MOA

Answer 64

Selective antagonist at N-type voltage-sensitive calcium channels on neurons​ Blocks calcium channels on primary nociceptive afferent neurons in dorsal horn of the spinal cord​

Question 65

Ziconotide pharmakinetics

Answer 65

Distributed through cerebrospinal fluid and then transported to systemic circulation

Question 66

Ziconotide ADRs

Answer 66

CNS and muscle injury​

Question 67

Ziconotide drug interactions

Answer 67

Formal studies not done​

Question 68

Ziconotide prep, dosage, admin

Answer 68

Intrathecal administration

Question 69

Dexmedetomidine

Answer 69

Selective alpha2-adrenergic agonist​ Acts in the CNS to cause sedation and analgesia​

Question 70

Dex uses

Answer 70

Short-term sedation in critically ill patients who are initially intubated and undergoing mechanical ventilation​ Sedation for nonintubated patients before or during surgical and other procedures​

Question 71

dex ADRs

Answer 71

Hypotension​ Bradycardia