Opioids

Question 1

MOA for opioid analgesia

Answer 1

1. Inhibition of pain signaling

2. Reduce CNS response to pain signal (pro-analgesic)

Question 2

One of the natural active constituents of opium, prototype

Answer 2

Morphine

Question 3

IM, SC, IV, oral

Readily absorbed, effect in 5-15 minutes, 4-5 hr duration

Answer 3

Morphine (12 H DOA with sustained release)

Question 4

Morphine: main metabolic pathway, active metabolites?

Answer 4

Glucuronidation (liver), morphine-6-B-glucuronide (long half-life) and morphine-3-B-glucuronide (seizures)

Question 5

Are there dosing considerations for morphine with impaired liver or kidney function?

Answer 5

Yes

Question 6

3 therapeutic effects of morphine:

Answer 6

Analgesia, sedation, euphoria

Question 7

T/F: Sedation arising from morphine will lessen with use (tolerance).

Answer 7

True

Question 8

MOA morphine analgesia (2)

Answer 8

Acts at peripheral and spinal levels to block pain transmission and acts at higher brain levels to block response to pain

Question 9

5 major side effects of morphine

Answer 9

Respiratory depression, nausea/vomiting, constipation, pupillary constriction, itching

Question 10

MOA of respiratory depression associated with morphine

Answer 10

Decreased sensitivity of chemoreceptor centers to plasma CO2 levels (hypoxic response still present)

Question 11

T/F: Tolerance does NOT develop against respiratory depression.

Answer 11

False (tolerance develops)

Question 12

CVD side effects of morphine

Answer 12

Mild, orthostatic hypotension due to histamine release (that also causes the itching)

Question 13

Immune system side effects of morphine

Answer 13

Inhibition, minor unless someone is already immune compromised

Question 14

Hormonal side effects of morphine

Answer 14

Altered effects, usually minor

Question 15

Biliary & urinary tract side effects of morphine

Answer 15

Increased pressure, may worsen biliary colic and urinary tract obstruction

Question 16

6 contraindications/limitations of morphine

Answer 16

1. Patients with decreased respiratory reserve (asthma, emphysema, cor pulmonale)
2. Head injuries
3. CNS tumors
4. Pregnancy
5. Neonates & elderly (much more sensitive)
6. Potential for dependence and misuse

Question 17

DDIs for all opioid analgesics

Answer 17

Other CNS depressants (sedatives, ethanol, antidepressants, etc.)

Question 18

Given orally, onset in 30-60 minutes, DOA 4-6 hours

Answer 18

Codeine

Question 19

Potency of codeine (fraction)

Answer 19

1/10 (used for milder pain)

Question 20

Metabolism of codeine (reaction, enzyme, product)

Answer 20

Demethylated by CYP2D6 to morphine

Question 21

Clinical uses of codeine (3ish)

Answer 21

1. Mild-moderate pain 2. With aspirin or APAP (additive effects)
2. Cough suppression (lower doses)

Question 22

Codeine vs. morphine: important differences (2)

Answer 22

More likely to cause constipation and less likely to cause addiction

Question 23

Oral, IV, IM, transdermal, intranasal, sublingual

Onset times differ depending on route, but generally rapid onset and short DOA (ex: few minute onset for oral)

Answer 23

Fentanyl

Question 24

Clinical uses of fentanyl (what type of pain?)

Answer 24

Chronic and breakthrough pain

Question 25

Fentanyl vs. morphine: differences

Answer 25

Fentanyl does not promote histamine release (itching), affects the cardiovascular system less than morphine, more likely to produce truncal rigidity, VERY HIGH addiction potential (rapid onset, short duration)

Question 26

More potent and lipid soluble than morphine, allowing for rapid CNS entry

Answer 26

Heroin

Question 27

Synthetic opioid with very effective oral administration, but also given IV at low doses

Answer 27

Methadone

Question 28

Metabolism enzymes and duration of methadone

Answer 28

CYP3A4 and CYP2B6, slowly

Question 29

Onset ~15-30 minutes, half-life 15 H when acute, but 22 H when chronic Longer DOA than morphine when used chronically

Answer 29

Methadone

Question 30

ADEs: serious cardiovascular events, like QT prolongation and torsades de pointes Parenterally, causes euphoria and dependence, but NOT orally

Answer 30

Methadone (CV events when dose is too high)

Question 31

Effects of partial agonists/mixed agonists compared to full

Answer 31

Less analgesic action, but less respiratory depression

Question 32

T/F: Partial agonists act as antagonists when in the presence of full agonists.

Answer 32

True, can precipitate withdrawal

Question 33

What are mixed agonists-antagonists?

Answer 33

Drugs that are primarily agonists are ONE RECEPTOR subtype, but primarily antagonists at ANOTHER RECEPTOR subtype

Question 34

Kappa agonist, mu antagonist

Answer 34

Nalbuphine (kappa analgesia with ceiling on mu respiratory depression)

Question 35

Not given orally, similar potency as morphine, CIII | Onset 15 minutes, DOA 4-6 hours

Answer 35

Nalbuphine

Question 36

Partial agonist at mu receptors, antagonist at kappa receptors

Answer 36

Buprenorphine (mu analgesia & respiratory depression ceiling without kappa side effects)

Question 37

Not given orally, 30X more potent than morphine, CIII

Answer 37

Buprenorphine

Question 38

Major use for buprenorphine= opioid dependence and cocaine abuse, much like methadone. How does its use differ from methadone?

Answer 38

Its partial mu agonist (antagonist!) properties precipitates withdrawal in addicts using morphine, heroin, or other full agonists

Question 39

ADEs: QT prolongation and torsades de pointes | Available IV, IM, buccal film, or subdermal implant

Answer 39

Buprenorphine

Question 40

Anti-diarrheal agent that uses opioids unwanted constipating effects for therapy!

Answer 40

Loperamide (Imodium)

Question 41

Can be taken orally, as action is limited to GI tract | Onset 2-4 hours, DOA 10-15 hr

Answer 41

Loperamide

Question 42

Diphenoxylate difference from loperamide

Answer 42

CV, limited abuse potential (loperamide available OTC, no CNS actions, no abuse)

Question 43

Antitussive effects, like codeine | NOT analgesic, but can still be abused

Answer 43

Dextromethorphan (Robitussin)

Question 44

Dextromethorphan MOA (suspected)

Answer 44

CNS NMDA receptor antagonist for antitussive effect

Question 45

Opioid antagonist for treating opioid-induced constipation

Answer 45

Methylnaltrexone

Question 46

MOA of methylnaltrexone | Administration

Answer 46

Blocks GI opioid receptors that mediate constipation, SC injection daily

Question 47

T/F: Methylnaltrexone crosses the blood-brain barrier, but does not significantly contribute to CNS effects.

Answer 47

False, does not cross the BBB

Question 48

Naloxone MOA

Answer 48

Competitive antagonist at opioid receptors

Question 49

T/F: naloxone works with the same efficacy for full and partial agonists.

Answer 49

False, works better with full agonists (partial agonists are highly potent and slowly dissociate from receptors)

Question 50

Opioid antagonist: Poor oral absorption, IV Rapid onset 2-5 minutes, DOA 30 minutes- 2 hours

Answer 50

Naloxone (Narcan)

Question 51

Used to counteract effects of opioids, particularly in life-threatening events of respiratory depression 1. After surgery 2. After overdose

Answer 51

Naloxone (Narcan)

Question 52

T/F: Naloxone is NOT effective in treating respiratory depression due to non-opioid CNS depressants, like benzodiazepines.

Answer 52

True

Question 53

Opioid antagonist: Very effective orally Long DOA ~ 24 H

Answer 53

Naltrexone

Question 54

Used for treating opioid dependence...PREVENTING effects of opioids, so requires a strong patient commitment

Answer 54

Naltrexone

Question 55

Added to opioid products to prevent abuse. When taken orally, no effect. When taken parenterally, blocks opioid receptor (precipitates withdrawal and/or prevents opioid effect)

Answer 55

Naloxone