Opioids

Question 1

What are the major effects of opioid pharmacodynamics?

Answer 1

analgesia - both sensory and emotional parts

respiratory depression

sedation or “euphoria” - often dysphoria if no pain prior, NO AMNESIA!

miosis

slowed peristalsis

nausea/vomiting

Question 2

What is the #1 way opioids kill people?

Answer 2

respiratory depression

Question 3

sedation vs. analgesia

Answer 3

not the same!

if someone is sedated, they can still say that they feel pain

natrual endpoints of opioid use - asleep or awake with no pain

Question 4

What are the characteristics of opioid miosis?

Answer 4

seen with all opioid agonists

no tolerance to this - hence useful in overdose dx

happens even in tolerant addicts

Question 5

How do opioids cause slowed peristalsis and nausea/vomiting?

Answer 5

slowed peristalsis - via enteric NS opioid receptors

nausea/vomiting - via chemoreceptor trigger zone

Question 6

What is Abstinence Syndrome?

Answer 6

withdrawal occurs after cessation of use

Question 7

What effects of opioids do people not become tolerant to?

Answer 7

miosis and constipation

Question 8

What effects of opioids can people become tolerant to?

Answer 8

euphoria

sedation

analgesia

N and V

respiratory

depression

Question 9

What is opioid withdrawal?

Answer 9

symptoms are of sympathetic overdrive:

• sweating
• HTN, tachycardia
• Hyperventilation
• Mydriasis

Except - darrhea, abdominal cramping due to opioid receptors on the gut wall

non-lethal (but doesn’t feel like it)

Question 10

What are the clinical signs of opioid overdose?

Answer 10

respiratory depression/arrest

sedation/unresponsive

miosis

ABCs (airway, breathing, circulation) - support ventilation

antagonist - Naloxone (reversal can be titrated)

Question 11

What are the drug interactions of opioids?

Answer 11

BIG concern is potentiating respiratory and sedative effects - benzo’s, barbituates, etc.

DO NOT combine sedatives with opioids

phenothiazines - used for nausea, may cause sedation and respiratory depression

antihistamines - used for itching, can cause sedation

Question 12

What are the opioid agonists?

Answer 12

morphine

codeine

hydrocodone

oxycodone

meperidine

fentanyl

hydromorphone

tramadol

Question 13

What are the opioid antagonist?

Answer 13

naloxone

naltrexone

Question 14

What are opioid agonist/antagonists?

Answer 14

nalbuphine

Question 15

What is an opioid partial agonist?

Answer 15

buprenorphine

Question 16

morphine

Answer 16

not very lipophilic vs fentanyl

Morphine is transdermal and not practical

IV dose slower onset/offset vs. fentanyl

5-10 min vs 1-2 min onset

histamine release significant - rash hypotension possible

Question 17

What are the major metabolites of morphine?

Answer 17

70% morphine 3-glucoronide (minimal activity)

30% morphine 6-glucoronide (incredibly potent! 10-100x more potent than morphine)

normally glucoronide can’t enter CNS, but in renal failure, it can enter CNS by mass effect

Question 18

Hydrmorphone (Dilaudid)

Answer 18

similar to morphine in action

no problematic metabolites

no significant histamine release

used in NMH instead of morphine

Question 19

codeine

Answer 19

prodrug - methylmorphine: low receptor affinity

10% metabolized to morphine (7-10% of population can’t do it)

considered a wek opioid though in high doses can still cause nausea and constipation via parent

Question 20

hydrocodone and oxycodone

Answer 20

codein related

hydrocodone - used with acetaminophen (Norco, Vicodin), maybe decreases abuse potential

oxycodone - as pill only in US (analgesia is via parent compound, immedate release pill and sustained release pill)

Question 21

fentanyl

Answer 21

very lipophilic - fast onset IV and crosses skin, buccal tissue

IV for O.R. anesthesia - fast onset, easy to titrate and short duration (good for outpations)

Question 22

transdermal fentanyl

Answer 22

slow onset - build up sub-q depot 1st

sustained release for chronic, cancer pain

NOT for ACUTE pain

2-4 hours before saturates fat and gets through

lasts for about 2-3 days

Question 23

buccal fentanyl

Answer 23

not as fast as IV or as short

still, faster than oral pill

NOT for sustained pain control

Question 24

meperidine

Answer 24

lipophilic, fast onset, not popular

metabilite - normeperidine

• half life 10 hrs
• normeperidine cleared by kidneys
• can cause seizures

don’t use in renal failure patients

Question 25

methadone

Answer 25

bioavailability of 0.9

NO active metabolites

long T(1/2) of 24hr (sometimes longer)

problem is accumulation - must be given more often than half-life (q8hr)

full effect not know for 3-5 half lives - accumulate drug faster than they should and overdose on it

Question 26

tramadol

Answer 26

an oral non-scheduled analgesic

technically a pro-drug

works by two mechanisms - mu receptor agonism and blocks reuptake of 5-HT and NE

mainly for mild-moderate pain

Question 27

How does naloxone work?

Answer 27

same basic structure as morphine

can knock morphine off of the receptors

used for opioid overdose

Question 28

naloxone

Answer 28

IV only - short half life of 1hr, duration 15 min - 4hr

VERY poor bioavialability - combine in opioid pills to prevent IV abust

competitive antagonist - can titrate and balance with morphine

• same basic structure as morphine
• can knock morphine off of the receptors
• used for opioid overdose

Question 29

What are the opioid receptors?

Answer 29

Mu, Kappa, Delta

• one gene codes for ecah

sybtypes come from splice variants

all involved in brain, spinal GI sites

Question 30

What are the effects of the Mu receptor?

Answer 30

analgesia

euphoria

dependence

respiratory depression

GI effects

puritis

Question 31

What is the effect of the Kappa receptors?

Answer 31

mild analgesia

less respiratory depression than Mu

psychomimetic effects (unlike euphoria)

Question 32

What are the effects of delta receptors?

Answer 32

unknown

Question 33

Where are the opioid receptor locations?

Answer 33

periaqueductal gray

spinal trigeminal nucleus

substantia gelatinosa

thalamus, amyglada

area postrema

brainstem ventillation nuclei

GI tract! (enteric nervous system)

Question 34

What is the mechanism of opioid receptors?

Answer 34

work via G receptor proteins which then:

• inhibit cellular adenylyl cyclase
• increase K+ currents and decrease Ca++ currents
• causes hyperpolarization
• decrease nociceptive transmission

also activate PAG - trigger descending inhibitory pathways

Question 35

What is the clinical relevance of opioid receptors?

Answer 35

interpersonal receptor density variability

different opioids have different receptor affinities - subtle differences between splice variant affinities, don’t know them all

different opioids have different effects in different patients - have to titrate opioid to analgesic effect

Question 36

What is the procedure if the side effects of opioids are present but there isn’t much analgesia?

Answer 36

change the opioid!!

Question 37

What is the elimination half life of opioids?

Answer 37

morphine, meperidien, hydromorphine, oxycodone around 2-3 hour half life

methadone notable at 24 hours - can range from 12-104 hours

fentanyl elimination half life - 3+ hours

Question 38

What are general characteristics of sustained release pills for opioids?

Answer 38

short T1/2 of most opioids limit duration

sustained release pill allows for matrix rlease drug during GI transit - if crushed/chewed pill dumps all immediately

sustained release allows q8 hr or q12 hr - morphine, oxycodone, hydromorphone in US

fentanyl - sustained release via patch

methadone - patch/matrix not needed

Question 39

What is the distinction between opioid, opiate, and narcotic?

Answer 39

opiates are medications derived from the opium poppy, and they include opium, codeine, and
morphine

‘Opioids’ are all substances that bind
to the opioid receptors present in many tissues

‘narcotic’ is irredeemably associated with illicit use of opioids, cannabinoids, stimulants such as cocaine and methamphetamine, sedative-hypnotics, and even (in some state regulations) anabolic steroids

Question 40

What are the weak opioids?

Answer 40

codeine is now the only weak opioid

Question 41

What are the strong opioids?

Answer 41

everything except codeine

Question 42

What are the four types of agonism?

Answer 42

agonists - mu receptor agonists

antagonists - mu receptor antagonists

mixed agonist/antagonist - kappa agonists/mu antagonists

partial agonist - partial mu agonist but HIGH affinity

Question 43

What are agonist/antagonist opioids?

Answer 43

kappa agonists and mu antagonists

ex. nalbuphine

never give to someone on chronic opioid user because of withdrawal

analgesia is kappa mediated

all seem to have ceiling effect and less GI side effects

Question 44

What are the partial agonist opioids?

Answer 44

partial mu agonism but HIGH affinity

buprenorphine

kappa antagonism, but is meaningless!

Question 45

What are the uses of agonist/antagonist opioids?

Answer 45

goal - less respiratory depression and sedation and euphoria via kappa

problem - kappa makes oyu nuts so not good in acute pain

do NOT use in opioid tolerant patient - triggers withdrawal

in low dose - reverse opioid side effects while getting some analgesia

Question 46

What are the uses of partial agonist opioids?

Answer 46

the only partial mu agonist

has a ceiling on agonism!

binds mu with HIGH affinity - higher than opioids, prevents other opioids from binding, and makes naloxone reversal difficult in OD

current use - opioid maintenance, ok for chronic pain

Question 47

What is the lipophilicity classification?

Answer 47

relase to BBB and spinal use

high lipophilicity - fast onset, short duration (ex. fentanyl, meperidine)

low lipohilicity - slow onset, long duration (morphine, hydromorphone)