Pain Opioids 3

Question 1

How does hydromorphone compare to morphine regarding

• lipid solubility
• Onset of action
• Potency

Answer 1

More lipid soluble
Faster onset
5X more potent

Question 2

What are the 2 metabolites of hydromorphone? How does the active metabolite compare to morphine-6-glucuronide

Answer 2

Hydromorphone-6-glucuronide
Hydromorphone-3-glucuronide
Hydromorphone-6-glucuronide less active at receptor than morphine-6-glucuronide

Question 3

What is the product of hydrocodone metabolism? What is the enzyme responsible?

Answer 3

Hydromorphone

CYP2D6

Question 4

When hydrocodone is combined with acetamenophen, you get _ (2)

Answer 4

Vicodin

Lortab

Question 5

What is oxycodone metabolized to? What us the enzyme responsible?

Answer 5

Oxymorphone

CYP2D6

Question 6

How is codeine related to morphine? What enzyme metabolizes codeine?

Answer 6

It is a prodrug that is demethylated to yield morphine

CYP2D6

Question 7

How is heroin related to morphine? What property makes it a drug of abuse?

Answer 7

It is converted to monoacetyl morphine, then into morphine in the brain
Euphoria, Lipid soluble, fast onset

Question 8

How is methadone administered? What makes it unique? What is it used for (2)?

Answer 8

Orally
Ultra long lasting (half life or 15-60 hrs)
Opioid addiction, pain management

Question 9

How does meperidine compare to morphine with regards to:

• Lipid solubility
• Potency

Answer 9

More lipid soluble

1/10 X potency

Question 10

What is the metabolic product of meperidine? Where does this occur? What are 2 potential side effects of this metabolite?

Answer 10

nor-meperidine
Liver
CNS stimulation, convulsions

Question 11

What patient subpopulation may be at risk for serious meperidine side effects?

Answer 11

Patients with renal failure, not cleared as needed

Question 12

What are the components of the serotonin syndrome triad?

Answer 12

Neuromuscular hyperactivity
Autonomic hyperactivity
Altered mental status

Question 13

What mu opioid agonist is associated with serotonin syndrome? This is especially true when combined with _ (2)

Answer 13

Meperidine

SSRIs or MAOs

Question 14

What is the activity of tramadol at the mu receptor? What other receptor does it function at?

Answer 14

Partial agonist

Inhibitor of the monoamine reuptake inhibitor

Question 15

What is ultracet? What enzymes metabolize tramadol / ultracet? Which gives its active metabolite?

Answer 15

Utracet = Tramadol + acetamenophen
CYP2D6 and CYP3A4
CYP2D6

Question 16

What is tapentadol? What enzyme metabolizes it? What advantage does it have over tramadol?

Answer 16

Partial mu agonist and inhibitor of the monoamine reuptake inhibitor
CYP2C9 and CYP2C19
Less pharmacogenetic variability

Question 17

What is the receptor activity profile for pentazocine, butorphanol and nalbuphine? What are these drugs used for (2)?

Answer 17

Kappa agonists, mu partial agonists or antagonists

Acute short term pain and to manage side effects

Question 18

What is the receptor activity profile for buprenorphine? How does its affinity for the mu receptor affect its clinical use? What can it be used for?

Answer 18

• Partial mu agonist, full kappa agonist
• Very high affinity at mu receptor, hard to displace, therefore hard to provide analgesia for surgical patients
• Drug abuse and addiction

Question 19

Regarding pharmacokinetics, where are majority of phase 1 enzymes found? (2)

Answer 19

Gut

Liver

Question 20

How can a clinician account for the variability of opioid activity from patient to patient?

Answer 20

Titrate to effect

Question 21

What are 2 mu agonists that can be used to treat diarrhea? What are their unique properties?

Answer 21

Diphenoxylate
Loperamine
Poorly / Not absorbed

Question 22

What are the 4 examples of opioid antagonists provided?

Answer 22

Naloxone
Naltrexone
Almivopan
Methylnaltrexone

Question 23

How do naloxone and naltrexone compare regarding duration of action and administration?

Answer 23

Naloxone is administered IV , naltrexone is oral

Naltrexone is also very long lasting

Question 24

A poorly absorbed orally active opioid antagonist that antagonizes the GI side effects of opioids. This describes _

Answer 24

Almivopan

Question 25

Quaternary ammonium derivative that is positively charged. IV peripherally restricted opioid antagonist for
constipation. This describes _

Answer 25

Methylnaltrexone

Question 26

2 opioid formulations designed to provide pain relief by be resistant to abuse is _

Answer 26

ER morphine with sequestered naloxone

Oxycodone-naloxone

Question 27

A prodrug for oxymorphone is _. The enzyme responsible for metabolism is _

Answer 27

Oxycodone

CYP2D6

Question 28

Why is acetaminophen, and not NSAIDs, combined with opioids?

Answer 28

Acetaminophen safer than NSAIDs, less side effects, therefore patient can use more of drug without problems. If patient stops an opioid combined with NSAIDs, can get withdrawal

Question 29

CYP2D6 is involved in the metabolism of a lot of opioids. What is a drug where its pharmacogenomic variability is actually clinically significant?

Answer 29

Dosing of codeine

Question 30

What is an advantage of the fentanyl patch? What is an advantage of oral fentanyl? Another use for fentanyl beyond pain relief is _

Answer 30

• Hard to abuse patch
• Rapid onset and potent orally
• Sedation

Question 31

What are 3 plausible explanations for variable responses to opioids between patients?

Answer 31

Mu receptor polymorphisms
Drug metabolisms differences
Increased drug efflux from tissues
** All related to pharamcogenetics **