Week 9 - Chapter 28 Opioid Analgesics, Antagonists, and Centrally Acting Nonopioid Analgesics

Question 1

Abstinence Syndrome

Answer 1

If opioids are withdrawn, an abstinence syndrome usually will follow.
The intensity and duration of the opioid abstinence syndrome depends on two factors: the half-life of the drug being used and the degree of physical dependence.

Question 2

Abuse

Answer 2

Abuse can be broadly defined as drug use that is inconsistent with medical or social norms. By this definition, abuse is determined primarily by the reason for drug use and by the setting in which that use occurs—and not by the pharmacologic properties of the drug itself. For example, whereas it is not considered abuse to administer 20 mg of morphine in a hospital to relieve pain, it is considered abuse to administer the same dose of the same drug on the street to produce euphoria.

Question 3

Addiction

Answer 3

Addiction is defined by the American Society of Addiction Medicine as a disease process characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm. Note that nowhere in this definition is addiction equated with physical dependence. In fact, physical dependence is not even part of the definition.

Question 4

Agonist-Antagonist Opioids

Answer 4

Pentazocine, nalbuphine, butorphanol, Buprenorphine

Question 5

Analgesics

Answer 5

drugs that relieve pain without causing loss of consciousness

Question 6

Cross-Tolerance

Answer 6

exists among the opioid agonists (eg, oxycodone, methadone, fentanyl, codeine, heroin). Accordingly, individuals tolerant to one of these agents will be tolerant to all the others. No cross-tolerance exists between opioids and general CNS depressants (eg, barbiturates, ethanol, benzodiazepines, general anesthetics).

Question 7

Delta Receptor

Answer 7

opioid analgesics do not interact with delta receptors.

Question 8

Dynorphins

Answer 8

peptides that act on kappa receptors

Question 9

Endorphins

Answer 9

peptides that act on mu and delta receptors

Question 10

Enkephalins

Answer 10

peptides that act on delta receptors

Question 11

Kappa Receptor

Answer 11

Analgesia, Sedation, Decreased GI motility

Question 12

Mu Receptor

Answer 12

Analgesia, respiratory depression, sedation, euphoria, physical dependence, Decreased GI motility.

Question 13

Narcotic

Answer 13

aka opioids

Question 14

Opioid

Answer 14

An opioid (previously known as a narcotic) is any drug, natural or synthetic, that has actions similar to those of morphine. The term opiate is more specific and applies only to compounds present in opium (eg, morphine, codeine).

Question 15

Patient-Controlled Analgesia (PCA)

Answer 15

PCA is a method of drug delivery that permits the patient to self-administer parenteral (transdermal, IV, subQ, epidural) opioids on an “as-needed” basis. PCA has been employed primarily for relief of pain in postoperative patients. Other candidates include patients experiencing pain caused by cancer, trauma, myocardial infarction, vaso-occlusive sickle cell crisis, and labor. As discussed below, PCA offers several advantages over opioids administered by the nurse.

Question 16

Physical Dependence

Answer 16

physical dependence is a state in which an abstinence syndrome will occur if the dependence-producing drug is abruptly withdrawn. Physical dependence is NOT the same as addiction.

Question 17

Pure Opioid Agonist

Answer 17

activate mu and kappa. examples: morphine and codeine

Question 18

Pure Opioid Antagonists

Answer 18

Naloxone. Antagonist of my and kappa. No analgesic effects.

Question 19

Tolerance

Answer 19

a state in which a larger dose is required to produce the same response that could formerly be produced with a smaller dose. Alternatively, tolerance can be defined as a condition in which a particular dose now produces a smaller response than it did when treatment began. Because of tolerance, dosage must be increased to maintain analgesic effects.

Question 20

Withdrawl Syndrome

Answer 20

Giving an opioid at any time during withdrawal rapidly reverses all signs and symptoms. Left untreated, the morphine withdrawal syndrome runs its course in 7 to 10 days. It should be emphasized that, although withdrawal from opioids is unpleasant, the syndrome is rarely dangerous.

Question 21

Morphine - Mechanism of Action

Answer 21

Morphine and other opioid agonists appear to relieve pain by mimicking the actions of endogenous opioid peptides, primarily at mu receptors.

Question 22

Morphine - Category

Answer 22

prototype of the strong opioid analgesics and remains the standard by which newer opioids are measured.

Question 23

Morphine - Use

Answer 23

analgesia, sedation, euphoria, respiratory depression, cough suppression, and suppression of bowel motility.

Question 24

Morphine - Adverse Effects

Answer 24

respiratory depression, constipation, orthostatic hypotension, urinary retention, cough suppression, biliary colic, emesis, elevation of intracranial pressure, euphoria/dysphoria, sedation, mitosis, birth defects, neurotoxicity, hormonal and immune changes due to prolonger use.

Question 25

Fentanyl - Mechanism of Action

Answer 25

metabolized by CYP3A4 (the 3A4 isoenzyme of cytochrome P450), and hence fentanyl levels can be increased by CYP3A4 inhibitors (eg, ritonavir, ketoconazole)

Question 26

Fentanyl - Category

Answer 26

Schedule II strong opioid analgesic

Question 27

Fentanyl - Use

Answer 27

surgical analgesia, chronic pain control, and control of breakthrough pain in patients taking other . REVERSAL IS NALOXONE

Question 28

Fentanyl - Adverse Effects

Answer 28

respiratory depression, sedation, constipation, urinary retention, and nausea.

Question 29

Codeine - Mechanism of Action

Answer 29

In the liver, about 10% of each dose of codeine undergoes conversion to morphine, the active form of codeine. The enzyme responsible is CYP2D6 (the 2D6 isoenzyme of cytochrome P450). Among people who lack an effective gene for CYP2D6, codeine cannot be converted to morphine, and hence codeine cannot produce analgesia. Conversely, among ultrarapid metabolizers, who carry multiple copies of the CYP2D6 gene, codeine is unusually effective.

Question 30

Codeine - Category

Answer 30

Schedule II Moderate to Strong Opioid Agonist

Question 31

Codeine - Use

Answer 31

relief of mild to moderate pain; cough suppression

Question 32

Codeine - Adverse Effects

Answer 32

Very rarely, severe toxicity develops in breast-fed infants whose mothers are taking codeine. The cause is high levels of morphine in breast milk, owing to ultrarapid codeine metabolism. Nursing mothers who are taking codeine should be alert for signs of infant intoxication—excessive sleepiness, breathing difficulties, lethargy, poor feeding—and should seek medical attention if these develop.

Question 33

Naloxone - Mechanism of Action

Answer 33

tructural analog of morphine that acts as a competitive antagonist at opioid receptors, thereby blocking opioid actions. Naloxone can reverse most effects of the opioid agonists, including respiratory depression, coma, and analgesia.

Question 34

Naloxone - Use

Answer 34

reversal for opioid “overdose”

Question 35

Naloxone - Category

Answer 35

Pure Opioid Antagonist

Question 36

Naloxone - Adverse Effects

Answer 36

In some cases of accidental poisoning, there may be uncertainty as to whether unconsciousness is due to opioid overdose or to overdose with a general CNS depressant (eg, barbiturate, alcohol, benzodiazepine). When uncertainty exists, naloxone is nonetheless indicated.

Question 37

Tramadol - Mechanism of Action

Answer 37

an analog of codeine that relieves pain in part through weak agonist activity at mu opioid receptors. However, it seems to work primarily by blocking uptake of norepinephrine and serotonin, thereby activating monoaminergic spinal inhibition of pain. Naloxone, an opioid antagonist, only partially blocks tramadol’s effects.

Question 38

Tramadol - Use

Answer 38

moderate to moderately severe pain. The drug is less effective than morphine and no more effective than codeine combined with aspirin or acetaminophen. Analgesia begins 1 hour after oral dosing, is maximal at 2 hours, and continues for 6 hours.

Question 39

Tramadol - Adverse Effects

Answer 39

serious adverse effects have been rare. Respiratory depression is minimal at recommended doses. The most common side effects are sedation, dizziness, headache, dry mouth, and constipation.

Question 40

Tramadol - Category

Answer 40

moderately strong analgesic