Wednesday, 8-24-Narcotics And Analgesics-Fitzpatrick

Question 1

How does an opioid agonist affect the pain impulse pre and post synaptically?

Answer 1

When opioid agonist occupies its receptor, blunts Ca influx and blunts Glu discharge pre-synapse, and increases K efflux post-synapse

Question 2

In terms of drugs that bind to mu opioid receptors:

___ are full agonists
___ are partial agonist/mixed
___ are antagonists

Answer 2

Fentanyl and morphine=full

Buprenorphine=partial/mixed

Naloxone and naltrexone=antagonist

Question 3

Which full agonist is more potent: fentanyl or morphine?

Answer 3

Fentanyl –> but both are equally efficacious

Question 4

In terms of the pain treatment ladder:

___ are used for mild pain

___ are used for moderate or persisting or uncontrolled pain

___ are used for severe or persisting or uncontrolled pain

Answer 4

NSAID and acetaminophen

Codeine, codeine-related +/- Acetaminophen, Tramadol

Morphine, fentanyl

Question 5

What is the opioid prototype?

What is the MOA of opioids?

What is the clinical utility of opioids?

Answer 5

Morphine

Mu receptor agonists

Tissue injury=acute stimuli > or equal to nerve injury

Question 6

What are the clinical effects of agonists acting at opioid receptors?

Answer 6

• analgesia (supra-spinal)
• euphoria
• CNS and resp depression
• drug dependence
• miosis
• GI, uterine motility

Question 7

What clinical effects can a person build up tolerance for morphine?

There is no tolerance to ___ with morphine

Answer 7

Analgesia, euphoria, sedation, nausea, resp depression

Miosis and constipation

Question 8

What are contra-indications for morphine regarding respiration?

Answer 8

Brain injury, emphysema

Question 9

What are some clinical indications for morphine?

Answer 9

Post-operative pain –> procedures and surgery
Cancer pain –> primary and metastatic malignancy
Other pain –> sickle cell crisis, trauma, severe diarrhea, dyspnea caused by pulmonary edema from LV failure

Question 10

Group 1 opioids are full agonists that can be given IV or PO. List the drugs:

Answer 10

Morphine
Methadone
Meperidine

Hydromorphone
Oxymorphone
Levorphanol

Question 11

Group 2 opioids are full agonists and short acting. List the drugs:

Answer 11

Fentanyl
Sufentanil
Remifentanyl

Question 12

Group 3 opioids are codein-related. List the drugs:

Answer 12

Hydrocodone

Oxycodone

Question 13

Which group 1 full agonists have high (good) oral bioavailability?

Answer 13

Methadone and Leveorphanol

Oral/parenteral potency ratio

Question 14

Describe the bioavailability of oral morphine:

Answer 14

POOR bioavailability –> 1st pass metabolism effect

Question 15

The pharmacokinetic properties of this opioid agonist drug are useful for withdrawal/maintenance and detoxification

Answer 15

Methadone

Question 16

Compare the half life and oral bioavailability of methadone vs morphine:

Answer 16

Methadone has higher t1/2 (27 hrs vs 2 hrs for morphine)

Methadone has better oral bioavailability (90% vs 20% for morphine)

Question 17

Methadone can affect cardiac electrical conduction, producing __ prolongation in acute overdose or during long-term methadone tx

Answer 17

QT-interval

Question 18

This mu agonist causes mydriasis. Abuse is difficult to detect via pinpoint pupils. Accordingly, those who abuse this drug can escape detection

Answer 18

Meperidine

Question 19

__ is a toxic metabolite of meperidine which accumulates and causes seizures

Answer 19

Normeperidine

Question 20

Which of the group 2 opioid agonists has affects as a kappa, delta, and mu agonist?

Answer 20

Sufentanil

Question 21

Compare the potency of Group 2 opioid agonists vs morphine and methadone (group 1 opioid agonists)

Answer 21

100x more potent than morphine and methadone

Question 22

___ is gaining popularity for providing analgesia for childbirth if regional anesthesia is either contraindicated or not desired. It is metabolized by plasma and tissue esterases. Although it transfers across the placenta, its rapid metabolism in the fetus lowers the risk for neonatal depression. Its rapid onset of action, within 1 minute following IV injection, is another advantage

Answer 22

Remifentanil

Question 23

___ is a strong mu agonist (meperidine analog), used in anesthesia, has a rapid onset and distribution (lipophilic), short DOA (procedures), transmucosal (lollipop), and can be given via transdermal patch delivery. There is high abuse potential via heating patches

Answer 23

Fentanyl

Question 24

__ is a group 3 mu partial agonist for moderate pain and cough. It has less potential for drug dependence and respiratory depression

Answer 24

Codeine

Question 25

Compare the oral bioavailability of codeine compared to morphine:

Answer 25

Reliable oral absorption--> 50% versus 20% for morphine

Question 26

Is the anti-tussive effect for cough relief with codeine mu dependent?

Answer 26

No, it is u-independent

Question 27

This a safer antitussive agent that relieves cough independently of opioid receptor. It is not an analgesic and not addictive

Answer 27

Dextromethophan

Question 28

Formulation of hydrocodone and oxycodone with acetaminophen complicates __ management

Answer 28

Overdose

Question 29

What phase 1 enzyme is responsible for converting codeine to the active metabolite morphine?

Answer 29

CYP2D6

Question 30

These opioids have a special use for anti-diarrhea with limited abuse potential:

Answer 30

Loperamide and diphenoxylate These interact with mu opioid receptor in the gut, have low solubility, and poor penetration of BBB

Question 31

__ is a moderate mu agonist, its active metabolite is N-desmethyl, has reliable oral absorption/bioavailability (70% vs 20% for morphine), analgesia for moderate pain, inhibits catecholamine reuptake (associated with seizures) and should be cautious with patients on tricyclic or SSRIs

Answer 31

Tramadol

Question 32

__ is a mixed kappa agonist plus mu partial agonist/ delta antagonist. Used for supra-spinal analgesia, can precipitate withdrawal (in abusers), and side effects include tachycardia, hallucinations

Answer 32

Pentazocine

Question 33

___ is a mu partial agonist plus kappa and delta antagonist used for analgesia. It can precipitate withdrawal in abusers. It is also used in office-based detox/maintenance in combo with naloxone

Answer 33

Buprenorphine

Question 34

__ is an illegal substance that penetrates the BBB rapidly --> exaggerated euphoria --> addiction liability

Answer 34

Heroin (Di-acetylmorphine)

Question 35

Maintenance with this drug in addition programs has the highest compliance (50-80%):

Answer 35

Methadone

Question 36

What are signs/symptoms of opioid analgesic overdose?

Answer 36

RR

Question 37

These mu receptor antagonists occupy, but do not activate mu receptors. They competitively inhibt (displace) heroin, morphine, fentanyl from mu receptors.

Answer 37

Naloxone (IV) and Naltrexone (PO)

Question 38

What is the antidote for opioid overdose?

Answer 38

Naloxone (IV) and Naltrexone (PO) In emergency setting, use Naloxone since it is parenteral. Naltrexone can be given after pt is revived in the ED setting since it is PO

Question 39

This mu receptor antagonist can reverse coma and respiratory depression ~1 minute after IV bolus. It has a short DOA of about 1-2 hrs and can lead to apparent "relapse" of overdose symptoms

Answer 39

Naloxone

Question 40

This mu receptor antagonist has a long DOA (48 hrs for single dose orally) in overdose

Answer 40

Naltrexone

Question 41

What strategies might work for opioid-induced side effects such as constipation?

Answer 41

Methylnaltrexone: a quaternary derivative of naltrexone with restricted ability to cross the BBB. Functions as a peripheral acting opioid antagonist, including actions on the GI tract to inhibit opioid-induced decrease GI motility and delay in GI transit time, thereby decreasing opioid-induced constipation. Does not affect opioid analgesic effects or induce opioid withdrawal symptoms

Question 42

Describe the pre- and post-synaptic pain impulse:

Answer 42

Afferent sensory signal --> opioid receptor unoccupied and an increasing influx of Ca in the pre-synaptic nerve increases glutamate discharge from pre-synaptic --> increase in NMDA-receptor Na influx on Post-synaptic side --> pain impulse