Opioid Narcotic Analgesics

Question 1

Endorphins

Answer 1

Mu Rc (supra-spinal analgesia)

Question 2

Dynorphins

Answer 2

Kappa Rc (spinal analgesia)

Question 3

Enkephalins/Endorphins

Answer 3

Delta Rc

Question 4

Mu opioid Rc - Full agonist

Answer 4

1. Fentanyl (more potent)

2. Morphine

Question 5

Partial agonist (Mu)/mixed (Mu/K/delta)

Answer 5

1. Buprenorphine (partial agonist/mixed)

2. Pentazocine (mixed)

Question 6

Mu opioid Rc - antagonist

Answer 6

1. Naloxone
2. Naltrexone
   BOTH inhibit heroin, morphine, fentanyl –> ANTIDOTE for opioid overdose

Question 7

Tolerance to morphine

Answer 7

Response dec over time –> increase dose or different opioid
NO TOLERANCE TO - miosis, constipation
Contraindication - brain injury, emphysema

Question 8

Group 1
Full agonists
Parenteral/Oral

Answer 8

1. Morphine (low oral:parenteral ratio)
2. Methadone (high O:P ratio)
3. Meperidine
4. Hydromorphine
5. Oxymorphine
6. Levorphanol (high O:P ratio)

Question 9

Group 2
Full agonists
Short acting

Answer 9

1. Fentanyl
2. Sufentanil (Mu, K, delta)
3. Remifentanyl - VERY short acting
4. Alfentanil
   This group is 100x more potent than morphine and methadone

Question 10

Group 3

Partial agonists

Answer 10

1. Codeine - high O:P ratio; low efficiency; give higher dose
2. Hydrocodone - usually given with acetaminophen
3. Oxycodone - usually given with acetaminophen

Question 11

Morphine

Answer 11

CYP 3A4 = normorphine (INACTIVE)
UGT 1A1/2B7 = Morphine-3-glucuronide and Morphine-6-glucuronide (ACTIVE)
Dehydrogenase = Hydromorphone (ACTIVE)

Question 12

Methadone

Answer 12

• useful for withdrawal/maintenance, detoxification
• affects electrical conduction of heart - QT interval prolonged in overdose/long term trt
• block K channel –> delayed repol (HERG channels)
• longer half life than morphine

Question 13

Meperidine

Answer 13

• eye: dilation
• Normeperidine (toxic) accumulates –> seizures
  Fentanyl –> meperidine –> morphine
  (faster –> slower onset)

Question 14

Remifentanyl

Answer 14

• childbirth analgesia
• metab by plasma and tissue esterases (rapid in fetus)
• RAPID onset/SHORT acting

Question 15

Fentanyl (lollipop)

Answer 15

• RAPID onset/SHORT duration (Lipophilic)
• transmucosal
• used for ‘break through pain’ due to morphine
• transdermal patch delivery (slow onset)
• NO active metabolite (like Hydromorphone and oxymorphone)

Question 16

Codeine

Answer 16

• less chance for resp depression
• moderate pain analgesia
• 50% oral absorption
• anti-tussive –> cough relief (Mu independent)
  Adverse effect - sleep apnea and death in kids
• CYP 3A4 = norcodeine (INACTIVE)
• UGT 2B7 - codeine-6-glucuronide (ACTIVE)

Question 17

Safer anti-tussive

Answer 17

Dextromethophan

• not analgesic/not addictive
• relieves cough INDEPENDENT of opioid Rc

Question 18

Minimal abuse - Gut & opioids

Answer 18

1. Loperamide

2. Diphenoxylate

Question 19

Loperamide

Diphenoxylate

Answer 19

• anti-diarrheals
• poor solubility
• poor BBB penetration

Question 20

Tramadol

Answer 20

• Mu-desmethyl (active metabolite)
• 70% bioavailability
• inhibit catecholamine release
• can cause seizures
• treats moderate/uncontrolled/persisting pain

Question 21

Pentazocine

Answer 21

• supra-spinal analgesia
• precipitates ‘withdrawal’
• tachycardia, hallucinations

Question 22

Buprenorphine

Answer 22

• precipitates ‘withdrawal’

- detox/maintained in combo with Naloxone

Question 23

Abuse potential opioids

Answer 23

Heroin

• di-acetylmorphine
• penetrates BBB rapidly –> euphoria

Question 24

Naloxone (IV)

Answer 24

• reverses coma/resp depression

- NOT ABSORBED FROM GUT

Question 25

Naltrexone (PO)

Answer 25

- long duration in overdose | - 45 hrs for single dose

Question 26

Acetaminophen

Answer 26

Liver toxicity!!!

Question 27

Methylnaltrexone

Answer 27

- quaternary derivative of naltrexone - cannot cross BBB - acts peripherally --> inhibits opioid induced decrease in GI motility - DECREASES CONSTIPATION - DOES NOT affect opioid analgesic affects