Opioid Antagonist And Analgesia

Question 1

What are key features of naltrexone as an opioid antagonist?

Answer 1

Similar actions to naloxone
Longer duration of action
Single oral dose blocks heroin/opioid effects for up to 48 hours
Used with clonidine for rapid opioid detoxification

Question 2

What is the primary clinical use of naloxone?

Answer 2

To reverse coma and respiratory depression from opioid overdose.

Question 3

How quickly does IV naloxone work?

Answer 3

30 secs

Question 4

What is naloxone’s mechanism of action?

Answer 4

A: Competitive antagonist at mu, kappa, and delta opioid receptors (highest affinity for mu).

Question 5

What is the half-life of naloxone?

Answer 5

30-81 mins

Question 6

Why is naloxone ineffective orally?

Answer 6

A: Due to extensive first-pass metabolism in the liver.

Question 7

What risk is associated with naloxone’s short half-life?

Answer 7

Re-sedation or return of respiratory depression after initial reversal.

Question 8

Q1: What is tramadol’s mechanism of action?

Q2: How is tramadol metabolized?

Q3: What is tramadol used for?

Q4: How does tramadol’s respiratory depression compare to morphine?

Q5: What is a major drug interaction risk with tramadol?

Answer 8

A: Binds to mu-opioid receptors and weakly inhibits norepinephrine and serotonin reuptake.

A: By CYP450 2D6 to an active metabolite with higher mu-receptor affinity.

A: Moderate to moderately severe pain.

A: It is less than that of morphine.

A: Serotonin syndrome when combined with SSRIs.

Question 9

Q: What are the key features of tapentadol?

Answer 9

A: Mu-opioid receptor agonist + norepinephrine reuptake inhibitor; treats moderate to severe pain; low drug interactions (not CYP450-dependent).

Question 10

What are the key features of nalbuphine and butorphanol?

Answer 10

A: Partial agonists at kappa and mu receptors; limited use in chronic pain; nalbuphine causes less dysphoria and has minimal cardiovascular effects compared to pentazocine.

Question 11

What are the key features and risks of pentazocine?

Answer 11

A: Kappa agonist, weak mu/delta antagonist; used for moderate pain; increases BP and heart workload; can cause dysphoria, hallucinations, and precipitate withdrawal in morphine users.

Question 12

What are the key therapeutic uses and features of buprenorphine?

Answer 12

A: Used for analgesia and opioid use disorder; partial mu-opioid agonist with high affinity and long duration; combined with naloxone to prevent abuse; safer alternative to methadone.

Question 13

Q: What are key features of dextromethorphan?

Answer 13

A: Antitussive opioid; non-addictive, less constipation than codeine, available OTC; acts on different receptors than analgesic opioids.

Question 14

What makes loperamide effective yet low-risk for abuse?

Answer 14

A: Slows GI motility; poor CNS penetration due to P-glycoprotein; low solubility prevents parenteral abuse.

Question 15

What is the clinical use and abuse deterrent of diphenoxylate?

Answer 15

Used for diarrhea with atropine; poor aqueous solubility reduces IV abuse risk.

Question 16

What are the main features of hydrocodone?

Answer 16

A: Oral opioid for pain and cough; metabolized by CYP2D6/3A4; similar potency to oxycodone; 4-hour half-life.

Question 17

What is the clinical significance of codeine metabolism by CYP2D6?

Answer 17

A: Codeine requires CYP2D6 to convert into morphine for analgesia; poor metabolizers get no pain relief, while ultra-rapid metabolizers risk toxicity—especially dangerous in breastfeeding infants.

Question 18

Q: What are key features and risks of meperidine use?

Answer 18

A: Strong opioid agonist with local anesthetic properties; not for long-term use due to normeperidine-induced seizures and neurotoxicity; causes pupil dilation and is contraindicated in elderly/renal impairment.

Question 19

What are the key features and clinical uses of methadone?

Answer 19

A: Full opioid agonist used for detox and maintenance in opioid use disorder; long half-life (15–40h), oral efficacy, suppresses withdrawal; risk of delayed respiratory depression with accumulation.

Question 20

Q: What are the key features of remifentanil?

Answer 20

A: Ultra-short-acting opioid; onset in 1–1.5 min; metabolized by plasma esterases (not liver/kidney); used for short, painful procedures via continuous IV infusion

Question 21

How does fentanyl’s potency compare to morphine?

Answer 21

A: Fentanyl is ~100x stronger; sufentanil is ~1000x stronger.

Question 22

What is the main caution with fentanyl patches?
.

Answer 22

A: Fever or heat can increase absorption, leading to overdose.

Question 23

Q: Why does fentanyl have a short duration despite high potency?

Answer 23

A: Rapid redistribution into peripheral tissues.

Question 24

Why is fentanyl safe in cardiac surgery?
What rare side effect does high-dose fentanyl cause?

Answer 24

A: Minimal myocardial depression and no histamine release.
A: Wooden chest syndrome (rigid chest muscles).

Question 25

What is carfentanil used for, and why is it dangerous? : What distinguishes fentanyl and its analogs in anesthesia?

Answer 25

A: Used in veterinary medicine; extremely potent and fatal in humans. A: High potency + rapid onset make them ideal for induction.

Question 26

What is oxycodone metabolized into, and why is it clinically significant?

Answer 26

A: Oxymorphone; it’s more potent and contributes to oxycodone’s analgesic effect and abuse potential Most Commonly abused drug

Question 27

How does hydromorphone differ from morphine in potency and solubility?

Answer 27

A: It is more potent and more lipid soluble.

Question 28

What is the onset and duration of oxymorphone after parenteral dosing?

Answer 28

A: Onset: 5–10 min; Duration: 3–4 hours.

Question 29

What makes heroin faster-acting than morphine? What is the primary excreted form of morphine? What active metabolite of morphine can accumulate in renal failure?

Answer 29

A: Higher lipid solubility due to 6-MAM formation allows faster CNS penetration. Morphine-3-glucuronide. A: Morphine-6-glucuronide.

Question 31

Why does morphine have slower CNS entry than fentanyl or heroin? Why is oral morphine less effective than parenteral? What are common absorption routes for morphine and related opioids?

Answer 31

It is less lipid-soluble. First-pass hepatic metabolism reduces its bioavailability. GI tract, rectal, buccal, nasal, and transdermal.

Question 32

What makes opioid analgesia unique? How do opioids cause respiratory depression? What are signs of opioid use involving the eye, cough, and trunk?

Answer 32

It reduces both physical and emotional pain sensations. By inhibiting brainstem respiratory centers and blunting CO₂ responsiveness. Miosis, cough suppression, and truncal rigidity.

Question 33

What is a common GI side effect of opioids and why? Name three non-CNS organ systems opioids affect and how? What immune and dermatologic side effects can opioids cause?

Answer 33

Constipation, due to slowed peristalsis and increased fluid absorption. Renal (decreased flow), uterine (prolonged labor), endocrine (↓LH, ↑ADH) Histamine-mediated itching and altered immune cell activity.

Question 34

What type of pain is best treated with opioids? What are three non-pain-related clinical uses of opioids? How do opioids assist in anesthesia?

Answer 34

Severe, constant pain such as that from cancer or terminal illness. Pulmonary edema relief, cough suppression, and diarrhea treatment. They provide sedation, anxiolysis, analgesia, and can be used epidurally or intrathecally due to dorsal horn action.

Question 35

Which effects of opioids do not develop tolerance? Where do opioids act to modulate descending pain pathways? How do opioids affect GABAergic neurons in the descending pain pathway? Where are opioid receptors located and what is their effect? What ion channels do opioids modulate to reduce pain?

Answer 35

Miosis and constipation. Periaqueductal gray (PAG), rostral ventral medulla, and dorsal horn of the spinal cord. They inhibit GABA release, leading to disinhibition of descending pain inhibition. In spinal cord and brain regions; they inhibit pain transmission. Inhibit Ca²⁺ influx (presynaptic) and increase K⁺ efflux (postsynaptic).

Question 36

What are the cellular effects of opioid receptor activation? Why should morphine be used cautiously in renal impairment? Which morphine metabolite is active and crosses the BBB? Which tissues accumulate opioids the most? Why are some opioids like oxycodone more effective orally?

Answer 36

Decreased Ca²⁺ influx, increased K⁺ efflux, and inhibition of neurotransmitter release. Active glucuronide metabolites can accumulate and cause toxicity. Morphine-6-glucuronide (M6G). Brain, lungs, liver, kidneys, spleen (high perfusion tissues). They undergo less first-pass metabolism.

Question 37

What is the function of the nociceptin/orphanin FQ system? What are the sources of endogenous opioid peptides? Name the three families of endogenous opioid peptides. What type of opioid is morphine, and which receptor does it target? What is the difference between opioids and opiates? What is the natural source of morphine?

Answer 37

Modulates nociception, reward, mood, anxiety, and cough; similar to dynorphin. POMC, proenkephalin A, and proenkephalin B. Endorphins, enkephalins, and dynorphins. Full agonist at the mu-opioid receptor. Opioids act on opioid receptors; opiates are natural alkaloids like morphine and codeine. The opium poppy (Papaver somniferum).