06b: Opioids

Question 1

(Opium/opiate/opioid) is naturally occurring alkaloid.

Answer 1

Opiate

Question 2

(Opium/opiate/opioid) is mixture of alkaloids from Papaver somniferum.

Answer 2

Opium

Question 3

(Opium/opiate/opioid) is any natural or synthetic compound with morphine-like properties.

Answer 3

Opioid

Question 4

Morphine falls into the category of (opium/opiate/opioid).

Answer 4

Opiate

Question 5

Morphine is opioid receptor (agonist/antagonist). Give another example in this category.

Answer 5

Agonist;

Fentanyl

Question 6

Buprenorphine is opioid receptor (agonist/antagonist).

Answer 6

Agonist-antagonist (binds multiple receptors)

Question 7

Naloxone is opioid receptor (agonist/antagonist).

Answer 7

Antagonist

Question 8

Morphine is (natural/synthetic), as is (heroin/codeine/fentanyl).

Answer 8

Natural; codeine

Question 9

Methadone is (natural/synthetic), as is (heroin/codeine/fentanyl).

Answer 9

Synthetic;

Fentanyl

Question 10

Most clinically important opioid analgesics are (selective/non-selective) (agonists/antagonists) to (X) receptor class. Give an example.

Answer 10

Selective; agonists;
X = mu (MOP)

Sufentanil

Question 11

T/F: All opioid receptors are RTKs.

Answer 11

False - all GPCRs

Question 12

Opioids generally work through which second-messenger pathway?

Answer 12

Go/Gi (inhibit AC, decrease cAMP)

Question 13

Opioid effects: (vasoconstriction/vasodilation), (brady/tachy)-cardia, (miosis/mydriasis).

Answer 13

Vasodilation, bradychardia, miosis

Question 14

Opioid effects: smooth muscle (X) and skeletal muscle (Y).

Answer 14

X = spasm
Y = hypertonus (stiffness)

Question 15

Opioid (mu) receptor class impacts (pre/post)-synaptic (afferent/efferent) neuron by (increasing/decreasing) Ca (uptake/release). What does this do?

Answer 15

Pre-synaptic; (primary) afferent
Decreasing uptake;

Decrease neurotransmitter release

Question 16

Opioids decrease release of which NT from primary afferents?

Answer 16

Substance P, ACh, NE, SA

Question 17

Opioid (mu) receptor class impacts (pre/post)-synaptic neuron by (increasing/decreasing) K (uptake/release). What does this do?

Answer 17

Post-synaptic;
Increasing
Release (outward K current);

Hyperpolarize (IPSP)

Question 18

List the three locations in CNS where opioids play a role.

Answer 18

1. Limbic system (impact affect to pain)
2. PAG (descending pain modulation)
3. Dorsal horn (primary afferent pain fibers)

Question 19

Clinical selection of an opioid is usually based on (X) considerations.

Answer 19

X = pharmacokinetic

Question 20

T/F: Pts, after opioid administration, typically report pain has vanished.

Answer 20

False - pain still present, but dulled and no longer bothers them as much

Question 21

T/F: Opioids can vary drastically in lipophilicity.

Answer 21

True - partition coeff of morphine 1.4 and fentanyl is 860

Question 22

Morphine: (slow/rapid) absorption and clearance. Relatively (hydrophobic/hydrophilic), so CNS penetration/exit are (slow/fast). This accounts for morphine’s (slow/fast) onset and (short/long) duration.

Answer 22

Rapid absorption/clearance;
Hydrophilic;
Slow;
Slow onset, long duration

Question 23

(Fentanyl/Codeine/Morphine) cleared by hepatic biotransformation.

Answer 23

All three (almost all opioids cleared by liver)

Question 24

Fentanyl: (slow/rapid) absorption and clearance. Relatively (hydrophobic/hydrophilic), so CNS penetration/exit are (slow/fast).

Answer 24

Rapid absorption/clearance;
Hydrophobic (extremely lipophilic!!)
Fast (effects rapidly parallel changes in plasma conc)

Question 25

Which property of (fentanyl/morphine) allows its administration via multiple routes?

Answer 25

Fentanyl; lipophilicity | transdermal patch, intranasal spray, buccal tablet, lollipop

Question 26

Conjugation, specifically (X), of morphine can result in (Y) product 15% of the time. This is problematic, especially in which patient population?

Answer 26

``` X = glucuronidation Y = morphine-6-glucuronide ``` Active metabolite, slow to clear, builds up in brain; renal failure patients

Question 27

Codeine undergoes (methylation/de-methylation) to become (X). This is a (minor/major) pathway of codeine metabolism.

Answer 27

O-Demethylation X = morphine Minor (10% of codeine) BUT accounts for nearly all opioid activity

Question 28

T/F: Most codeine metabolism (80%) results in inactive metabolites.

Answer 28

True - only morphine product active

Question 29

T/F: Opioids most likely to cause problems in hepatic failure, since most cleared by liver.

Answer 29

False - renal failure because many opioids have polar active metabolites (buildup if clearance is slow)

Question 30

Opioids: polymorphisms in clearance may be good or bad, depending on which two things?

Answer 30

1. Effect of metabolite | 2. Activity of parent drug

Question 31

T/F: Analgesia from opioids is always accompanied by some respiratory depression/effect.

Answer 31

True

Question 32

Opioids: depression of ventilatory response to (high/low) (CO2/O2) levels. The extent of this resp depression is dose-(dependent/independent).

Answer 32

High CO2, low O2 | Dose-dependent

Question 33

(X) is the major toxicity of opioids and nearly always cause of death from overdose. Treatment is (Y).

Answer 33

``` X = respiratory depression Y = naloxone ```

Question 34

T/F: Tolerant individuals requiring large amounts of opioids for analgesia are at proportionately increased risk for resp depression.

Answer 34

False

Question 35

N-Methylnaltrexone is (centrally/peripherally)-acting (agonist/antagonist) of mu opioid receptors. What's it used for?

Answer 35

Peripherally; Antagonist Treats opioid-induced constipation/urinary retention without antagonizing analgesia (can't enter CNS)

Question 36

Opioids cause nausea/vomiting via which mechanism?

Answer 36

Direct stimulation of CTZ (chemoreceptor zone) in area postrema (floor of fourth ventricle); this activates vomiting center in medulla

Question 37

Opioid-induced hives by (X) release (is/isn't) indicative of (Y) reaction. What's the mechanism?

Answer 37

X = His; Isn't (no IgE); Y = Anaphylactoid Competitive displacement of His from tissue mast cells

Question 38

T/F: Opioid physical dependence is the same as opioid addiction.

Answer 38

False

Question 39

Opioid withdrawal is treated with:

Answer 39

small dose of opioid

Question 40

List some symptoms of opioid withdrawal.

Answer 40

1. Rhinorrhea 2. Vomit/diarrhea 3. Gooseflesh/shaking 4. Mydriasis 5. Sweating (diaphoresis)

Question 41

Opioid addiction: agonist maintenance utilizes which drugs? What's the method of administration?

Answer 41

Methadone or Buprenorphine; Orally (decrease HIV/hepatitis seroconversion)

Question 42

Methadone maintenance to treat opioid addiction has which disadvantages?

Answer 42

1. Special license required 2. Separate from med care 3. Limited availability 4. Stable/unstable pts mixed 5. No privacy (social stigma) 6. Can't "graduate" from program