OPIOIDS

Question 1

what is the source of nociceptive somatic pain?

Answer 1

tissues (skin, muscle, joints, bones, ligaments)

often known as musculoskeletal pain

Question 2

what is the source of nociceptive visceral pain?

Answer 2

internal organs of the main body cavities (thorax, abdomen, pelvis)

Question 3

characterize somatic nociceptive pain vs. visceral pain

Answer 3

• somatic pain – sharp and well localized, can be reproduced by touching or moving the area/tissue involved
• visceral pain –poorly localized, dull pain (ache, cramping). frequently produces referred pain to the back

Question 4

differentiate useful medications for somatic vs. visceral pain

Answer 4

• somatic pain – may respond to combinations of weak or strong opioids AND NSAIDS
• visceral pain – very responsive to weak and strong opioids

Question 5

name a natural opioid

Answer 5

morphine

Question 6

name a synthetic opioid

Answer 6

fentanyl

Question 7

name a semisynthetic opioid

Answer 7

heroin

Question 8

name an opioid agonist

Answer 8

morphine

Question 9

name an opioid agonist/antagonist

Answer 9

nalbuphine

Question 10

name an opioid antagonist

Answer 10

naloxone

Question 11

what is the mechanism of action of opioids?

Answer 11

bind specific G protein-coupled receptors (in brain and spinal cord regions) involved in transmission and modulation of pain

Question 12

where do opioid agonists work?

Answer 12

• opioid receptors in the pre/post-synaptic CNS

* peripheral afferent nerves

Question 13

what endogenous ligands do opioids mimic the effects of?

Answer 13

• enkaphalins
• endorphins
• dynorphins

Question 14

what neurotransmitters are released in response to pain (release is decreased with opioids)

Answer 14

acetylcholine, dopamin, norepi, substance p

Question 15

which opioid receptor’s 1º action is analgesia, produces N/V, pruritits, and bradycardia, and has low abuse potential?

Answer 15

Mu1

Question 16

which opioid receptor is found only in the spinal cord (as opposed to spinal AND supraspinal)?

Answer 16

Mu2

Question 17

Mu1 and Mu2 both produce euphoria. which one also produces sedation?

Answer 17

Mu2

Question 18

which opioid receptors are responsible for physical dependence?

Answer 18

Mu2 and delta

Question 19

which opioid receptor does not produce respiratory depression?

Answer 19

Mu1

Question 20

which opioid receptor is responsible for dysphoria and diuresis?

Answer 20

kappa

Question 21

which opioid receptor is the principle site for agonist-antagonists, and is highly resistant to high intensity pain?

Answer 21

kappa

Question 22

where does nalbuphine work?

Answer 22

nalbuphine is an agonist-antagonist opioid – agonist at kappa receptors, and an antagonist at mu receptors

Question 23

three opioid receptors modulate the body’s ability to retain or excrete urine. describe the two

Answer 23

• kappa receptors produced diuresis (increase excretion)

* delta and Mu1 receptors produce urinary retention

Question 24

which receptors are responsive to endorphins, morphine, and synthetic opioids?

Answer 24

Mu1 and Mu2

Question 25

which receptors are responsive to dynorphins?

Answer 25

kappa

Question 26

which receptors are responsive to enkaphalins?

Answer 26

delta

Question 27

where are the targets of neuraxial opioids?

Answer 27

mu receptors in substantia gelatinosa of spinal cord

Question 28

what kind of pain are neuraxial opioids designed to suppress?

Answer 28

visceral pain

Question 29

what are the 4 classic side effects of neuraxial opioids?

Answer 29

pruritis, N/V, urinary retention, ventilatory depression

Question 30

what are the dosing recommendations for morphine (IV, epidural, intrathecal)

Answer 30

10mg IV, 1mg epidural, 0.1mg intrathecal (1/10 ratio; very hydrophilic)

Question 31

what are the dosing recommendations for hydromorphone (IV, epidural, intrathecal)

Answer 31

1mg IV, 0.2mg epidural, 0.04mg intrathecal (1/5 ratio; intermediate hydro-/lipo-philicity

Question 32

what are the dosing recommendations for fentanyl (IV, epidural, intrathecal)

Answer 32

100mcg IV, 33mcg epidural, 6-10mcg intrathecal (1/3 – 1/5 ratio; very lipophilic)

Question 33

how well are opioids absorbed?

Answer 33

* well absorbed by many routes | * some have high first pass metabolism (PO)

Question 34

how well are opioid distributed?

Answer 34

* rapidly leave blood compartment for highly perfused areas | * muscle and fat act as a reservoir

Question 35

describe the metabolism of opioids

Answer 35

* converted to polar metabolites then excreted by kidneys * morphine-6-glucoronide (4-6x analgesic potency than morphine – morphine is a prodrug) * tissue esterases (heroin, remifentanil) * normeperidine (demerol)

Question 36

what are the cardiovascular side effects of opioids?

Answer 36

* decreased sympathetic tone * decreased BP * decreased HR * minimal contractility effects

Question 37

what are the cardiovascular side effects of demerol?

Answer 37

anti-muscarinic effect (like atropine) – increase HR

Question 38

what are the respiratory effects of opioids?

Answer 38

* respiratory depression due to agonist effect at Mu2 * dose dependent depression of ventilatory response to CO2 * increased PaCO2 (almost becomes an anesthetic) * decreased RR * increased tidal volume * decreased minute ventilation * cough suppression (dextramethorphan – no analgesia or ventilatory depression)

Question 39

what are the CNS effects of opioids?

Answer 39

* sedation and analgesia vs. euphoria * reduces MAC * decreased CBF and CMRO2 * increases ICP with hypoventilation * seizures with meperidine use (normeperdine buildup) * miosis (edinger-wetphal nucleus of oculomotor nerve – no developed tolerance)

Question 40

describe biliary colic side effect of opioids

Answer 40

* spasm of sphincter of Odi (can present similarly to angina) * less with meperidine * naloxone relieves pain * glucagon 2mg IV reverses

Question 41

how are opioid side effects expressed in the GI?

Answer 41

* N/V * constipation * delayed gastric emptying * biliary colic

Question 42

how are opioid side effects expressed in the GU?

Answer 42

* urinary retention due to increase in tone of ureter and vesicle sphincter

Question 43

how do opioids affect histamine release?

Answer 43

increase histamine release – flushing, itching (more with morphine and meperidine)

Question 44

describe side effects observed in the thoracic cavity

Answer 44

truncal rigidity

Question 45

for which side effects do pts develop tolerance?

Answer 45

tolerance to depression of ventilation

Question 46

what is the onset, peak effect, and duration times of morphine?

Answer 46

* onset: 15-30min * peak effect: 45-90min * duration: 3-4hr

Question 47

how is morphine metabolized?

Answer 47

metabolized via conjugation with glucuronic acid in hepatic, extra hepatic, and kindneys

Question 48

what is the active metabolite of morphine?

Answer 48

morphine-6-glucaronide | * accumulation of morphine and metabolite in kidney failure pts leading to prolonged narcosis and ventilatory depression

Question 49

how potent is meperidine compared to morphine?

Answer 49

0.1 potency of morphine

Question 50

meperidine peak effect, duration

Answer 50

* peak effect: 5-7min | * duration: 2-4hr

Question 51

describe the local/atropine-like side effects of demerol

Answer 51

* block Na channels | * tachycardia, dry mouth, mydriasis

Question 52

how is demerol most of used?

Answer 52

Tx for post op shivering (12.5-25mg)

Question 53

fentanyl peak effect, duration

Answer 53

* peak effect 3-5min | * duration 30-60min

Question 54

how much fentanyl undergoes 1st pass pulmonary uptake?

Answer 54

75% (metabolized in lungs, not liver)

Question 55

what characteristic of fentanyl makes it last so long?

Answer 55

highly lipid soluble and protein bound

Question 56

which opioid is hemodynamically stable?

Answer 56

fentanyl

Question 57

induction dose – fentanyl

Answer 57

2-6mcg/kg with a sedative hypnotic

Question 58

what is the infusion rate of fentanyl

Answer 58

0.5-5mcg/kg/hr

Question 59

how potent is sufentanil compared to fentanyl?

Answer 59

10X as potent as fentanyl (greater affinity for opioid receptor – great for neurosurgery)

Question 60

peak, duration – sufentanil

Answer 60

same as fentanyl — peak 3-5min, duration 30-60min

Question 61

what is the dosing of sufentanil?

Answer 61

* 0.3-1.0mcg/kg 1-3min before DL | * 0.5mcg/kg followed by 0.5mcg/kg/hr

Question 62

how potent is alfentanyl compared to fentanyl?

Answer 62

1/10 as potent as fentanyl

Question 63

what procedures is alfentanyl good for?

Answer 63

anesthetic for RBB, DL | * 5-10mcg/kg provide good analgesia with rapid recovery

Question 64

how potent/long acting is remifentanyl compared to fentanyl?

Answer 64

similar potency to fentanyl, short duration (~10min)

Question 65

where is remifentanyl metabolized?

Answer 65

plasma and tissue esterases

Question 66

compare dilaudid to morphine

Answer 66

* 8x more potent than morphine but shorter acting (~2hr) * more sedation but less euphoria * less histamine release

Question 67

what are opioid antagonists useful for?

Answer 67

Tx overdose, respiratory depression

Question 68

what is the duration of opioid antagonists?

Answer 68

30-45min

Question 69

what is the dose of opioid antagonists?

Answer 69

1-4mcg/kg