236. Pharm, Opioids, Pain I/II

Question 1

Types of Pain Fibers

Types of Neurochemicals in pain

Answer 1

A-delta: fast pain
C fibers: slow pain
Both explain “double pain”

Pain initiators: Glutamate, Substance P (central)
Pain inhibitors: Serotonin, Norepinephrine, Endorphins

Question 2

What are the pain pathways? What is gate control theory? How do opioids act on pain pathway?

Answer 2

Somatosensory Pathway: pain, touch, temp, proprioception

Anterolateral pathway: Spinothalamic tract for pain, temp, crude touch, nerve crosses midline at level of dorsal root

Gate: non-painful stimuli can distract/inhibit painful stimuli
Periaqueductal Gray: descending inhibitory pain pathway

Opioids: block ascending pain pathway, turn on descending pathway through disinhibition, which decreases pain

Question 3

What are the three opioid receptors? What do they do? Where are they located?

Answer 3

1. Mu: analgesia, euphoria, respiratory depression, dependence, miosis, GI effects, pruritis
2. Kappa: mild analgesia, less respiratory depression, psychomimetic effects
3. Delta: unknown fx

Locations: Brain SC and GUT (all together)

Question 4

What are the two mechanisms for opioid action?

Answer 4

1. Decrease nociceptive transmission by binding to pre and post synaptic receptors (hyperpolarize membranes)
2. Activate PAG (descending inhibitory pathway) - inhibits GABA interneruon = disinhibits pain inhibitory neuron!

Question 5

Opium vs. Opiate vs. Opioid vs. Narcotic

Answer 5

Opium: juice of poppy
Opiate: derived from opium
Opioid: natural and synthetic drugs that bind opioid receptors (all opiates + more)
Narcotic: ANY substance that induces sleep, acts on opioid receptor or is illicit

Question 6

tolerance v. dependence v. addiction v. withdrawal

Answer 6

T: need more dose to achieve affect, can become tolerant to everything except MIOSIS
D: occurs if med is stopped and pt has sx of withdrawal
W: sympathetic overdive: anxiety, insomnia, diaphoresis, HTN, tachycardia, hyperventilation, diarrhea, abd cramp (not fatal)
Addition: drug misuse/abuse, NOT dependence NOR tolerance

Question 7

Morphine

agonism, lipophilicity, side effects, metabolism

Answer 7

Agonist, prototypical opioid
Hydrophilic - delayed BBB transit - delayed onset
SE: histamine release (rash, hypotension)
metabolism: in liver - M3G (seizures), M6G (analgesia, SE more potent than morphine)
Kidney excretes metabolites

Question 8

Oxycodone (agonism, effect, metabolism, use)

Answer 8

Agonist, semisynthetic
Direct analgesia
M: to oxymorphone - 14x more potent
Immediate release/extended release option

Question 9

Codeine (agonism, metabolism, SE)

Answer 9

PRODRUG (agonist)
10% metabolized to morphine (analgesia - some white people cannot metabolize it)
SE: nausea/constipation

Question 10

Hydrocodone (agonism, names, metabolism)

Answer 10

Agonist
Norco/Vicodin
M: to hydromorphone

Question 11

Hydromorphone (agonism, lipophilicity, SE, metabolism)

Answer 11

Agonist, Hydrophilic
SE: better than morphin, less rash, sedation N/V
M: to H3G - no analgesia, but some weak morphine-like SE

Question 12

Fentanyl (agonism, lipophilicity, route)

Answer 12

Agonist, Highly Lipophilic
75-125x more POTENT (give micro-grams!)
IV: in ORs/ICUs - fast onset, short duration
Transdermal: slow onset, sustained release, avoids gut
Sublingual: more expensive

Question 13

Merperidine (agonism, lipophilicity, mechanism, metabolism)

Answer 13

Agonist, lipophilic with rapid onset
Also potent inhibitor of serotonin reuptake
M: normerperidine - Long t1/2, CNS seizures

Question 14

Tramadol (agonism, mechanism, use)

Answer 14

Agonist (technically prodrug)
M: mu receptor agonist and block serotonin/norep reuptake to further inhibit pain
Use: mild-moderate pain

Question 15

Naloxone (agonism, use)

Answer 15

ANTAGONIST - IV

Short half life to reverse opioid overdose, poor bioavilability (use in opioid pills to prevent IV abuse)