Class #14 - Opioids

Question 1

Pain signaling?

Answer 1

Firing of Aδ (delta) nerve fibers and C nerve fibers respond to tissue injury -> Spinal cord -> relay in dorsal horn ->ascending pathway to thalamus (pain, emotional response) -> Descending pathway to relay to inhibit pain response

Question 2

Opiods actions?

Answer 2

1. Brain - reduce emotional reaction to pain

2. CNS: Block ascending and activate descending pathways for reduction of pain

Question 3

3 majors types of endogenous opioids?

Answer 3

Enkephalins
Endorphins
Dynorphins

Question 4

Methyl-morphine =

Answer 4

Codeine, added methyl at position 3 and now only 10% as potent as morphine.

Question 5

% of morphine and codeine in poppy latex

Answer 5

10% and 0.5%

Question 6

Diacetyl-morphine=

Answer 6

Heroin, makes it more potent IV

Question 7

opiates vs opiods

Answer 7

Drugs derived from opium poppy;

Any compound that acts on opiods receptor in brain (includes natural, semi-synthetics and synthetics opiods)

Question 8

Weak agonist eg.

Answer 8

Methadone

Question 9

Antagonists?

Answer 9

Naltrexone and naloxone

Question 10

Opioids receptors and the one predominantly use for pain relief?

Answer 10

Mu, delta and kappa

Mu

Question 11

Structure and function:
1. Hydroxyl site
2. Amine group
Eg. Naloxone

Answer 11

1. Affects affinity
2. Change efficacy of drug
   Eg. Big affinity, but null efficacy

Question 12

Opioids pharmacodynamics general (3)?

Answer 12

1. Pre-synaptic receptors reduce release of NT (afferent)
2. Post-synaptic receptors hyper-polarize (afferent)
3. Increase descending inhibitory neurons

Question 13

Opioids pharmacodynamics: Pre-synaptic receptors ?

Answer 13

Morphine binds on GP+ coupled with Mu receptors -> decrease release cAMP -> decrease synaptic intake of Ca++ reducing release of NT (afferent)

Question 14

Normal depolarization causes ___ influx into the neuron causing_____?

Answer 14

Ca++ -> release of NT in synaptic cleft

Question 15

Opioids pharmacodynamics: Post-synaptic receptors?

Answer 15

hyper-polarize (afferent): Mu GPCR -> increase output of K+ out of neuron

Question 16

Opioids pharmacodynamics: Descending inhibition

Answer 16

1. Inhibits primary afferent neuron
2. Serotonergic and noradrenegric inhibits pain and homeostasis held by GABAminergic inhibitory neuron which inhibits the inhibitory descending pathways.
3. Opioids inhibit the GABA which allows proper inhibition of afferent pain signal

Question 17

Opioids major site of action

Answer 17

Spinal cord

Question 18

Opioids receptors are all?

Answer 18

GPCR bound to ion channel or affecting cAMP (having effect on gene transcription in cells)

Question 19

1.Nociceptor vs 2.neuropathic vs 3.psychogenic pain

Answer 19

1. Peripheral injury: somatic affecting skin, bone, muscles. Visceral affecting organs
2. Damage to nervous system: peripheral, nerve route or CNS.
3. Pain enhanced by psy. problem

Question 20

opioids block other sensations?

Answer 20

No, only pain

Question 21

Opioids other effects? and receptors

Answer 21

Cough suppression, inhibit GIT (μ and k), euphoria, vomiting (acts on 3 sites of CTZ to cause vomiting) respiratory depression (μ), miosis (inhibition of normal inhibition of constriction), decrease urine output (triggers ADH release), contract musc. in bladder and sphincter = want to pee but cant.

Question 22

Pain reduction only with Mu receptors?

Answer 22

Majors, but also kappa (κ) and delta (δ)

Question 23

Morphine Absorption?

Answer 23

Best parenteral, b/c lots first pass. Best route IM

Question 24

Morphine crossing blood-brain barrier in %

Answer 24

20%

Question 25

Morphine t1\2

Answer 25

2-4 hours

Question 26

morphine excretion?

Answer 26

Urine

Question 27

Metabolite after oral morphine ?

Answer 27

Nomorphine: psychoactive and neurotoxic

Question 28

Metabolite after parenteral morphine?

Answer 28

(60%) morphine-3-glucoronide: Inactive (t1/2 4h)

40%) morphine-6-glocoronide: Highly active (t1/2 = 3h, renal failure >50%

Question 29

Morphine pharmacodynamics of GIT.

Answer 29

Mu receptors in myenteric plexus (miniature brain of GIT) = decrease peristalsis and cessation of coordinated propulsive wave, increase rectal tone and decrease colonic mucosa secretion, increase H2O absorption

Question 30

High tolerance for?

Answer 30

analgesia, N/V, euphoria, sedation, cough suppression

Question 31

Moderate tolerance for?

Answer 31

Bradycardia

Question 32

No tolerance to

Answer 32

miosis, constipation, convulsions and antagonists

Question 33

Codeine pharmacokinetics? if dont have the right CYP for effect?

Answer 33

Converted to morphine by CYP2D6

Converted to norcodeine by CYP3A4

Question 34

Partial agonist?

Answer 34

Buprenorphine

Question 35

demerol (Meperidine) metabolized to?

Answer 35

Normeperidine - as effective as morphine with fewer AE

Question 36

Fentanyl time to peak with duration?

Answer 36

5min, 45min

Question 37

Loperamide?

Answer 37

cannot get through BBB

Question 38

Naltrexone vs naloxone

Answer 38

Better PO and last 24h, better parenteral

Question 39

Codeine and tamoxifen?

Answer 39

Both met. by 2D6.