Opioid Analgesics

Question 1

Endogenous neuropeptide transmitters

Answer 1

Beta-endorphin
Enkephalin
Dynorphin

Question 2

Opioid receptor classes

Answer 2

Mu
Delta
Kappa

Question 3

Ligand-receptor matches

Answer 3

B-endorphin -> mu
Enkephalin -> mu and delta
dynorphin -> kappa

Question 4

Intracellular pathway for Opioid receptors

Answer 4

coupled to inhibitory G-protein
ligand or drug binds -> alpha unit inhibits cAMP -> this inhibits opening of Ca and Na channels -> leads to hyperpolarization and reduction in AP
Beta unit -> still opens K channels -> K leaves the cell -> hyperpolarizes even more
this leads to inhibition of the neuron

Question 5

Two locations of action for opioids

Answer 5

Brain and spinal cord

Question 6

Where do opiates work

Answer 6

midbrain and brainstem

Question 7

How do opiates work in the brain

Answer 7

disinhibit the descending pathway

Question 8

GABAergic neuron in the midbrain/brainstem release GABA which inhibits_____

Answer 8

NE and 5HT release

Question 9

NE and 5HT do what

Answer 9

inhibit pain (descending pathway)

Question 10

If you inhibit the GABAergic neuron with an opioid, what will happen

Answer 10

inhibit GABA release leads to release of 5HT and NE to activate descending pathway and block/reduce pain

Question 11

Nociceptive circuitry in the spinal cord

Answer 11

Ascending pathway: A-delta and C-fibers release glutamate and substance P -> activate projection neurons -> send pain message to brain
Descending pathway: NE and 5HT released into spinal cord -> bind and activate interneuron -> interneuron makes enkephalin -> inhibits release of glutamate and substance P -> inhibits pain mechanism

Question 12

Presynaptic terminals of sensory neurons have

Answer 12

opioid receptors

Question 13

what happens if an opioid binds to presynaptic mu or delta receptor

Answer 13

release enkephalin -> inhibit release of glutamate and substance P

Question 14

What activates projection neurons; what inhibits them?

Answer 14

activates: glutamate and substance P
inhibits: release of enkephalin

Question 15

Can opioid agonists activate all receptors

Answer 15

Yes, with the exception of fentanyl which shows strong mu preference

Question 16

Binding preference of opioids

Answer 16

mu > delta > kappa

kappa not used much b/c of SE

Question 17

Morphine and analogs

Answer 17

morphine is gold standard

most commonly used

Question 18

Morphine

Answer 18

MS contin; Kadian

Question 19

Oxycodone

Answer 19

Oxycontin

slightly higher potency 1:1.5 oxy:morphine

Question 20

Hydromorphone

Answer 20

Dilaudid
morphine alternative
3-5x more potent than morphine, orally

Question 21

Codeine

Answer 21

pro-drug
poor analgesic
can increase analgesic efficacy of NSAIDs

Question 22

Fentanyl

Answer 22

Highly potent mu receptor agonist
80-100x more potent than morphine
HIGH lipid solubility
SHORT duration of action
often transdermal patch or lozenge for chronic/breakthrough pain

Question 23

Fentanyl analogs (3)

Answer 23

Alfentanil (Alfenta): ultra-short acting (5-10 min)
Sufentanil (Sufenta): 50-10x more potent than fentanyl
Remifentanil (Ultiva): very very short acting (1-4 min)

Question 24

Tramadol

Answer 24

Ultram
weak mu receptor agonist
inhibits 5-HT and NE reputake -> prolongs effects
Alpha-2 agonist

Question 25

Methadone

Answer 25

Dolophine long acting agonist similar potency to morphine Often used as maintenance tx for addicts

Question 26

Buprenorphine

Answer 26

``` Subutex mu partial agonist long duration of action moderate to severe pain tx of physical dependence on opioids ```

Question 27

Suboxone

Answer 27

buprenorphine/naloxone combo agonist and antagonist prevents abuse - if crushed/compromised naloxone release and buprenorphine won't work

Question 28

Weak opioids

Answer 28

codeine | tramadol

Question 29

strong opioids

Answer 29

morphine and analogs fentanyl methadone buprenorphine

Question 30

WHO analgesic ladder

Answer 30

1. non-opioid +/- adjuvant 2. weak opioid for mild to moderate pain +/- non-opioid, +/- adjuvant 3. strong opioid for moderate to severe pain +/- non-opioid, +/- adjuvant

Question 31

SE of opioids

Answer 31

``` Nausea constipation sedation respiratory distress -> at high doses Miosis (OD) ```

Question 32

why do opioids cause respiratory distress

Answer 32

act in brainstem -> pons and medulla involved in modifying respiratory rate

Question 33

What is a peripheral SE and tx opioid use

Answer 33

constipation methylnaltrexone (relistor) OR alvimpoan (entereg) opioid receptor antagonists, do not cross BBB

Question 34

SE with long term use

Answer 34

tolerance physical dependence addiction

Question 35

Hydrocodone + acetaminophen

Answer 35

Vicodin, Lortab | Opioid combo tx

Question 36

Hydrocodone + ibuprofen

Answer 36

Vicoprofen | Opioid combo tx

Question 37

Oxycodone + acetaminophen

Answer 37

Percocet | Opioid combo tx

Question 38

Oxycodone + ibuprofen

Answer 38

Combunox | Opioid combo tx

Question 39

Oxycodone + aspirin

Answer 39

Percodan | Opioid combo tx

Question 40

Why have opioid combo tx? (2 reasons)

Answer 40

1A. Acetaminopen or NSAIDs produce additive/synergistic effect 1B. Thus, a lower opioid dose is needed to achieve the same effect 2. reduction in opioid dose reduces occurrence of SE