Pain & Opioids

Question 1

Semi-synthetic opioids

Answer 1

• chemical modification of the morphine molecule

- heroin (diacetylmorphine), thebaine, oxycodone, hydrocodone, hydromorphone

Question 2

Synthetic opioids

Answer 2

-manufactured by synthesis rather than chemical modification of the morphine molecule

• morphine derivative: levorphanol, nalbuphine
• benzomorphan methadone derivatives
• benzomorphan derivatives: pentazocine
• phenylpiperidine derivatives: meperidine, fentanyl, alfentanil, sufentanil, remifentanil

Question 3

Opioid receptors

Answer 3

-all 4 are G protein receptor and inhibit adenylate cyclase and cyclic adenosine monophosphate (cAMP) production

Mu-1, Mu-2
Delta
Kappa

Question 4

Mu receptors

Answer 4

Mu 1 - analgesia

Mu 2 - hypoventilation, physical dependence

Question 5

Generalized effects of exogenous opioids at the Mu-1 receptors include which two of the following? (supraspinal, spinal analgesia, physical dependence, constipation)

Answer 5

supraspinal, spinal analgesia

Question 6

The respiratory depressant effects of the opioid agonists are produced by action at which receptor?

Answer 6

Mu2

Question 7

Which opioid does NOT have an active metabolite? (Fentanyl, Meperidine, Morphine, Oxycodone)

Answer 7

Fentanyl

Question 8

Which opioid receptor is responsible for shivering postoperatively?

Answer 8

Kappa

Question 9

Which opioid receptor is involved in the physical dependence of opioid addiction?

Answer 9

Primiarly Mu 2 (also detla)

Question 10

Of the opioid medications which one has constant clearance and is unaffected by liver or renal disease?

Answer 10

Remifentanil

Question 11

Match opioid receptors with endogenous opioids:

[mu, delta, kappa] to [endomorphins, endorphins, enkephalins, dynorphins]

Answer 11

Mu: endomorphins, endorphins, enkephalins

Delta: endorphins and enkephalins

kappa: dynorphins

Question 12

2 chemical classes of opioid alkaloids?

Answer 12

1. phenanthrenes

2. benzylisoquinolines

Question 13

Opioid MOA

Answer 13

• Done largely by presynaptic inhibition via Ca++ ch inactivation & reduced Ca++ influx which reduces NT release (Ach, D, NE, SubP).
• increased K+ conductance (hyperpolarizes and prevents neuronal excitation/propagation)

Question 14

metabolism & excretion of opioids is via

Answer 14

hepatic metabolism for ALL (except remifentanil which is metabolized by non-specific esterases)

renal excretion for ALL (with some biliary, morphine)

Question 15

CYP enzymes inovlved

Answer 15

CYP 2D6, 3A4, 2B6

Question 16

active metabolite of morphine

Answer 16

morphine 6 gucuronide M6G

accounts for about 10% of morphine’s metabolism

Question 17

Opioid effects: CNS

Answer 17

analgesia, sedation, euphoria/dysphoria

Question 18

Opioid effects: CV

Answer 18

decreased tone & vasodilation

bradycardia

Question 19

Opioid effects: Pulm

Answer 19

• depresses RR and rhythm (slow/deep) primarily through Mu2 in the brainstem
• decreased responsiveness to hypercarbia
• decrease cough

Question 20

Opioid effects: ridgiidty

Answer 20

• cause skeletal muscle rigidity, especially thoracic and abdominal muscles (may involve actions with central mu receptors interacting with dopaminergic and GABA pathways)
• decrease in chest-wall compliance and constriction of pharyngeal and laryngeal muscles can become difficult to ventilate

Question 21

opioid effects: GI

Answer 21

PONV
GI constipation or ileus
increase biliary pressure, spasm of sphincter of oddi

Question 22

Naturally occurring opioids

Answer 22

morphine

codeine

Question 23

opioid partial agonists or agonist/antagonists

Answer 23

buprenorphine
butorphanol
nalbuphine

Question 24

opioid antagonists

Answer 24

naloxone
nalmefene
naltrexone

Question 25

synthetic codeine analog

Answer 25

tramadol

Question 26

non-narcotic analgesics

Answer 26

NSAIDS (ketorolac, ibuprofen) | acetaminophen

Question 27

receptor activation causes presynaptic inhibition of NTs release (what NTs are involved)

Answer 27

Ach Dopamine norepi substance P

Question 28

all opioid receptors are what type?

Answer 28

G-protein receptors and inhibit adenylate cyclase and cyclic adenosine monophosphate (cAMP) production

Question 29

True/False: naloxone and other opioid antagonists work at all 4 opioid receptors?

Answer 29

True

Question 30

Which opioid receptor is responsible for dysphoria and sedation?

Answer 30

kappa

Question 31

Which opioid receptors are responsible for miosis?

Answer 31

Mu1 | Kappa

Question 32

Which opioid receptor is responsible for bradycardia and hypothermia?

Answer 32

Mu1

Question 33

Which opioid receptor is responsible for euphoria?

Answer 33

Mu1

Question 34

Which opioid receptor is responsible for urinary retention?

Answer 34

Mu1 | Delta

Question 35

Opioid effects: cutaenous changes

Answer 35

flushed, warm, urticaria, puritis

Question 36

Order the context-sensitive half-time for a 4 hr infusion from shortest to longest (alfentanil, fentanyl, remifentanil, sufentanil)

Answer 36

``` Shortest 1. Remifentanil 2. sufentanil 3. alfentanil 4. fentanyl Longest ```

Question 37

Anesthesia's uses for opioids

Answer 37

- analgesia - blunting SNS response to intubation or surgical stimulation - sedation - reduces the amount of VA needed for MAC Meperidine - post-op` shivering

Question 38

Fentanyl IV push dose for analgesia

Answer 38

dose: 25-150 mcg onset: 3-5 min

Question 39

Fentanyl infusion rate

Answer 39

1-2 mcg/kg/hr

Question 40

Alfentanil loading dose & maintenance rate

Answer 40

loading dose: 35-70 mcg/kg (1500-5000 mcg in 70kg pt) onset: 1-2 min maintenance: 0.25-0.5 mcg/kg/min

Question 41

Remifentanil loading dose & maintenance rate

Answer 41

loading dose: 1-2 mcg/kg (70-140 mcg in 70kg pt) onset: 1 min maintenance: 0.05-0.25 mcg/kg/min

Question 42

Order of onset/peak for bolus injection, fastest to longest(alfentanil, fentanyl, remifentanil, sufentanil)

Answer 42

``` Fastest 1. Remifentanil 2. alfentanil 3. Fentanyl 4. sufentanil 5. morphine Longest ```

Question 43

most common pharmacokinetic interaction in opioid pharmacology?

Answer 43

combined IV opioids and propofol -due to hemodynamic changes induced by propofol and their impact on pharmacokinetic processes, opioid concentrations may be larger when given with continuous propofol

Question 44

most common pharmacodynamic interaction in opioid pharmacology?

Answer 44

synergistic interaction that occurs when opioids are given combined with sedatives - ex: when given with volatile anesthetics, they reduce the MAC of the VA. (MAC reduction can be substantial, but not complete) - can also be given with propofol or other hypnotics

Question 45

effects of increased age on opioids

Answer 45

-in general older patients have lower central clearance and higher potency (lower EC50)