Opioids

Question 1

What are the two opioid antagonists? What are their uses?

Answer 1

Naloxone - Overdose antidote (short duration, supportive therapy still needed)
Naltrexone - EtOH abuse.

Question 2

What is Buprenorphine used for?

Answer 2

Opioid abuse (partial agonist)

Question 3

What is Dextromethorphan’s use?

Answer 3

Anti-tussive

Question 4

Which phenanthrenes are moderate agonists & more useful with acetaminophen or aspirin?

Answer 4

Oxycodone & codeine

Question 5

How much can shivering increase O₂ consumption?
By what mechanism does meperidine treat shivering?

Answer 5

500%
↑ kappa receptor agonism & serotonergic effects.

Question 6

What is the most potent fentanyl derivative?

Answer 6

Carfentanil (10,000:1 morphine ratio)

Question 7

What is the primary use of Meperidine?
What cardiac effects are seen with it?

Answer 7

Post-op shivering
neg inotrope, + chronotrope

Question 8

What is methadone’s usefulness?
Why is this?

Answer 8

Suppression of opioid withdrawal symptoms (and chronic pain)
Long Half-Life = 25-50 hours

Question 9

What is heroin used for in the UK?

Answer 9

Palliative Care

Question 10

What structure is indicated in the figure below?
What types of opioids are associated with this structure?

Answer 10

Phenylpiperidine
Fentanyl & Meperidine

Question 11

What structure is indicated in the figure below?
What opioids are seen with this structure?

Answer 11

Phenylheptylamine
Very strong (Methadone)

Question 12

What structure is indicated in the figure below?
What strength is typically seen with these opioids?

Answer 12

Phenanthrene
Very strong (morphine, hydromorphone, heroine)

Question 13

What can occur when opioids are given to a pregnant mother?

Answer 13

Fetal Dependence

Question 14

Why are opioids partially contraindicated in head injuries?

Answer 14

↑ Resp depression

Question 15

What is the treatment for opioid induced hyperalgesia?

Answer 15

Wean opioid
GABA analogs

Question 16

What is the mechanism for opioid induced hyperalgesia?

Answer 16

Sensitization of MuOR-1K variant & ↑cAMP

Question 17

What is opioid induced hyperalgesia?
How many patients will experience this?

Answer 17

Increased pain response secondary to chronic use
30% of chronic users develop this

Question 18

What symptoms would be seen in severe opioid withdrawal?

Answer 18

Mydriasis
Hyperthermia
N/V/D
Anxiety/Hostility

Question 19

What mild symptoms might be seen from opioid withdrawal?

Answer 19

Piloerection
Hyperventilation
Lacrimation
Rhinorrhea
Yawning

Question 20

How quickly does opioid tolerance build?
What is the probable mechanism for this?

Answer 20

Rapidly
β-arrestin pathway

Question 21

What drug is indicated for post-operative shivering?

Answer 21

Demerol (meperidine)

Question 22

Why is morphine used in Acute Coronary syndrome?

Answer 22

↓ anxiety
↓ HR (and thus metabolic demand)
↓ pain

Question 23

What is the treatment for Acute Coronary Syndrome?

Answer 23

Morphine
Oxygen
Nitroglycerin
Aspirin

Question 24

What drug can cause respiratory depression when given with loperamide?
Why?

Answer 24

Quinidine
Blocks ABCB1 so loperamide accumulates and affects CNS.

Question 25

What does Loperamide do? Why?

Answer 25

Antidiarrheal opioid with no CNS effects due to GI ABCB1 clearance.

Question 26

Is tolerance developed to the constipatory effects of opioids?

Answer 26

No

Question 27

What effects may opioids have on the cardiovascular system? What is the exception?

Answer 27

Indirect CNS bradycardia Meperidine (Demerol) has antimuscarinic traits = ↑HR.

Question 28

What symptom of opioid organ system effects is always present with opioid use & no tolerance develops to it?

Answer 28

Miosis (pupillary constriction)

Question 29

Which opioid receptors are responsible for analgesia? Which opioid receptor is responsible for CNS respiratory depression & dependence/addiction?

Answer 29

Mu, delta, & kappa. Mu

Question 30

What opioid pathway leads to decreased effect & opioid tolerance?

Answer 30

G-protein independent pathway with ERK, JNK & β-arrestin. (ERK = E receptor Kinase, JNK = Janus Kinase)

Question 31

How do μ(mu) opioid receptors suppress pain?

Answer 31

Gᵢ = ↓AC → ↓cAMP = ↑pK⁺, ↓pCa⁺⁺ = Hyperpolarized neuron.

Question 32

Where are mu opioid receptors located on neurons?

Answer 32

Pre-synaptic & post-synaptic neurons

Question 33

What type of receptor are opioid receptors?

Answer 33

Gᵢ GPCRs

Question 34

What mediator is utilized with κ(kappa) receptors?

Answer 34

Dynorphins

Question 35

Differentiate full agonist, partial agonists, & antagonists of the opioid receptors. Give examples for each.

Answer 35

Full Agonists (strong to moderate effect) morphine, fentanyl, etc. Partial Agonists (moderate to mild effect) codeine, oxycodone, etc. Antagonists (Reversal) Naloxone

Question 36

What are the other opioid receptors aside from μ(mu) opioid receptors?

Answer 36

δ(delta) & κ(kappa) receptors.

Question 37

What is the primary opioid and endogenous ligand receptor? What endogenous ligands are used by this receptor?

Answer 37

μ(mu) opioid receptors Endorphins

Question 38

Which spinal tract is suppressive to painful stimuli?

Answer 38

Spinomesencephalic through μ(mu) opioid receptors in the periaqueductal gray matter.

Question 39

What are the three pain tracts of the CNS (discussed in lecture)?

Answer 39

Spinothalamic Spinoreticular Spinomesencephalic

Question 40

What mediators of pain (discussed in lecture) are released in response to tissue damage?

Answer 40

Bradykinin Prostaglandins Glutamate Substance P

Question 41

What fiber type can suppress fast pain?

Answer 41

Aβ through suppression of Aδ fast pain.

Question 42

Most pain receptors are _____ ______ endings.

Answer 42

free nerve

Question 43

Is most pain signaling hierarchical or diffuse?

Answer 43

Hierarchical

Question 44

Tachykinins use _________ __ receptors and have a __________ effect on pain signaling.

Answer 44

Substance P; excitatory

Question 45

What CNS effects does ACh have?

Answer 45

Learning & Memory Sleep-wake cycles Arousal & sensory information

Question 46

Which area of the brain is associated with ACh diffusion? What neurotransmitter does ACh have a similarity to in the CNS?

Answer 46

Pontine Nuclei Serotonin/Melatonin

Question 47

Which diffuse system area of the brain is associated with NE?

Answer 47

Locus Coeruleus

Question 48

Where is dopamine produced?

Answer 48

Substantia Nigra & Ventral Tegmental Area

Question 49

Where is serotonin produced?

Answer 49

Raphe Nuclei

Question 50

How do non-specific, diffuse systems differ from relay systems?

Answer 50

Monoamine Transmitters used (NE, Dop, 5-HT) Slower Diffuse throughout the CNS. (en-passant synapses used)

Question 51

How does an axoaxonic interaction differ from a feedback or feed-forward neuron interaction?

Answer 51

Inhibition/excitation occurs at the axon rather than the neuron body.

Question 52

Are feed-forward & feed-back systems inhibitory or excitatory?

Answer 52

They can be both.

Question 53

Explain the mechanism of a feed-forward response.

Answer 53

Neuron A excites an interneuron which then inhibits Neuron

Question 54

Explain the mechanism of a feed-back response. What is the purpose of this system?

Answer 54

Excitatory neuron depolarizes an inhibitory interneuron which suppresses the initial excitatory neuron. Seizure prevention from constant excitatory stimulation.

Question 55

What specific type of neuron is pertinent to feed-forward & feed-back responses in relay systems?

Answer 55

Interneurons

Question 56

What are hierarchical systems?

Answer 56

Multiple Neurons linked to one another for signaling.

Question 57

What are the three endogenous ligands pertinent to pain signaling?

Answer 57

Endorphins (1°) Enkephalins (pain signaling) Dynorphins (pain signaling)

Question 58

Naloxegol

Answer 58

- Opioid antagonist - derivative of morphine - naloxegol (gut)

Question 59

tramadol

Answer 59

Phenylpiperidines classification - has SNRI activity - racemic mixture - safer alternative considered moderate agonist.

Question 60

percadan/percocet

Answer 60

oxycodone + acetaminophen = percocet oxycodone + aspirin = percodan these combination are said to be more effective than codeine & oxycodone alone. (phenanthrenes)

Question 61

dilaudid

Answer 61

Hydromorphone (phenanthrenes) strong agonist for severe pain