Pharmacology of Opioid

Question 1

What opioids are considered to be in the class “high efficacy analgesics” (strong agonist)?

Answer 1

-morphine
-fentanyl
-methadone
-meperidine
-oxycodone
-hydromorphone

Question 2

What opioids are considered to be in the class “low-medium efficacy oral analgesics” (mild-moderate agonist)?

Answer 2

-codeine
-hydrocodone
-tramadol

Question 3

What opioids are considered to be in the class “mixed receptor agonist/antagonist”?

Answer 3

-buprenorphine
-nalbuphine

Question 4

What drugs are opioid antagonist?

Answer 4

-naloxone
-naltrexone

Question 5

What drug are non-analgesic opioids?

Answer 5

-dextromethorphan
-loperamide

Question 6

What are the therapeutic effects of opioids?

Answer 6

-analgesia (pain relief)
-cough suppression (mediated by DM receptors- not opioids)
-anesthesia
-sedation
-euphoria
-diarrhea treatment
-acute pulmonary edema

Question 7

Define: Equi-analgesia

Answer 7

all “full-agonists” (high efficacy) can achieve same maximal effect if dose is adjusted for binding affinity and route administration. morphine milligram equivalents (MME) is used to calculate and compare total daily dose of opioids (1mg morphine/day= 1MME)

Question 8

How do opioids cause analgesia?

Answer 8

-increase the pain threshold
-increase the pain tolerance

Question 9

Describe: Methadone

Answer 9

long-acting, replacement therapy to treat heroin addiction

Question 10

Describe: Meperidine

Answer 10

short-term therapy (<48 hours) due to toxic metabolite

Question 11

What are the indications of high efficacy opioid analgesics?

Answer 11

-severe pain
-adjunct in anesthesia (fentanyl, morphine)
-pulmonary edema (morphine only)

Question 12

What are the indications of low-medium efficacy opioid analgesics?

Answer 12

-mild-moderate pain
-cough suppression (codeine)

Question 13

Describe: Codeine

Answer 13

used for anti-tussive and anti-diarrheal effects (usually, not for pain)

Question 14

Describe: Tramadol

Answer 14

also blocks reuptake of NE or serotonin

Question 15

Describe: Buprenorphine

Answer 15

partial agonist at mu and antagonist at kappa, longer duration of action(4-8h), commonly paired with naloxone (suboxone) for treatment of opioid addiction

Question 16

Describe: Nalbuphine

Answer 16

agonist at kappa receptors and antagonist at mu, commonly used to reverse pruritis (itchy skin) that is a side effect of opioid agonists

Question 17

What are the indications of mixed agonist/antagonist?

Answer 17

moderate pain

Question 18

What is the cause of death from an opioid overdose?

Answer 18

respiratory depression

Question 19

What are the symptoms of opioid overdose?

Answer 19

the triad: coma, respiratory depression, pinpoint pupils

Question 20

Contraindications: Opioids

Answer 20

-impaired pulmonary function= may exacerbate symptoms
-head injuries
-pregnancy
-substance abuse history
-impaired hepatic/renal function
-use caution when combining with sedative-hypnotics or antipsychotic tranquilizer

Question 21

What is the main route of metabolism for opioids?

Answer 21

glucuronidation and demethylation in the liver

Question 22

What is the duration of action of opioids?

Answer 22

3-4 hours

Question 23

What is the antidote for opioid overdose?

Answer 23

opioid antagonists

Question 24

What drugs are opioid antagonists?

Answer 24

-naloxone (Narcan)
-naltrexone

Question 25

Describe: Naloxone

Answer 25

-opioid antagonist -duration of action= 1-2 hours, may need to repeat doses when treating an overdose, can be administered: (injection (healthcare professional), auto injector, nasal spray(Narcan) (OTC))

Question 26

What drugs are peripherally-acting mu-opioid receptor antagonists?

Answer 26

-methylnaltrexone -alvimopan -naloxegol -naldemedine

Question 27

What is the clinical use of peripherally-acting mu-opioid antagonists?

Answer 27

opioid induced constipation

Question 28

What can induce opioid withdraw?

Answer 28

-stopping opioid doses -antagonists (ex naloxone) -mixed agonist/antagonists (ex buprenorphine)

Question 29

What is the timeline of opioid withdraws?

Answer 29

begins 6-10h after last dose, peak at 36-48 hours, and subsides in 5-7 days- not life threatening, but very uncomfortable

Question 30

What are the symptoms of opioid withdraw?

Answer 30

-early symptoms= "flu-like", watery eyes, runny nose, yawning, goosebumps -late symptoms= restlessness and irritability, nausea and vomiting, increase heart rate and blood pressure, chills and sweating, muscle aches, diarrhea, mydriasis (pupil dilation), drug cravings

Question 31

What are symptoms of opioid withdrawal in neonates?

Answer 31

-blotchy skin coloring -diarrhea -excessive or high pitched crying -rapid breathing -poor feeding -sleep problems

Question 32

Describe: Naltrexone

Answer 32

-opioid antagonist -long duration of action (>10h)

Question 33

Describe: Methadone

Answer 33

-slow acting mu-opioid agonist -long duration of action (t1/2= 4-130h)= daily dosing at a clinic -replacement therapy

Question 34

Describe: Buprenorphine

Answer 34

-partial agonist of mu receptors, antagonists at kappa and delta (less efficacious than morphine) -replacement therapy -long duration of action (t1/2=40h)

Question 35

What type of pain can opioids treat?

Answer 35

-nociceptive pain (associated with injury and/or inflammation) -acute nociceptive pain (use with chronic pain is associated with tolerance and dependence) -cancer pain

Question 36

What are the CDC Guidelines for use of opioids for chronic pain?

Answer 36

1. opioids are not first-line or routine therapy for chronic pain 2. establish goals 3. discuss benefits and risks and availability of nonopioid therapies 4. use immediate-release opioids when starting 5. prescribe no more than needed 6. do not prescribe ER/LA opioids for acute pain 7. follow-up and re-evaluate risks and reduce dose or taper to discontinue if needed 8. check PDMP for high dosages and prescriptions from other providers 9. use urine testing 10. avoid using benzodiazepines with opioids 11. arrangement treatment for opioid use disorder if needed

Question 37

What signaling proteins are activated when opioid agonists bind to mu receptors?

Answer 37

G(i/o) signaling pathway which is responsible for pain-relieving effects and beta-arrestin that is responsible for the unwanted side effects: euphoria (addiction), respiratory depression, and gastrointestinal effects

Question 38

Describe: Oliceridine (Olincyk)

Answer 38

-MOA: selective full agonist at mu receptors, suggested it could be a biased agonist -indication: acute severe pain for when IV analgesics are required but alternative treatment is inadequate