Narcotic Pharmacology

Question 1

Three endogenous opioid receptors and transmitters:

Answer 1

Mu Receptor: Endorphins
Delta Receptor: Enkephalins and Endorphins
Kappa Receptor: Dynorphins

Question 2

Mu receptor actions:

Answer 2

• Good for acute pain
• Strongest response
• Spinal and Supraspinal Analgesia
• Slow GI transit
• Hormone release

Question 3

Delta receptor actions:

Answer 3

• Spinal and supraspinal analgesia

- Hormone release

Question 4

Kappa receptor actions:

Answer 4

• Only good for low level background pain not acute
• Spinal and supraspinal analgesia
• Psychomimetic -> Dysphoric Pain relief not euphoric

Question 5

Endorphin Functions:

Answer 5

• Modulate pain impulse in periphery
• Stimulate release of ADH, prolactin, ACTH and GH
• Inhibit release of LH, FSH, thyrotropin

Question 6

Opiate receptors:

Answer 6

• All are GPCR
• Reduce inward Ca current
• cAMP formation activating PKA

Question 7

Morphine:

Answer 7

• Opiates
• Act on Mu Delta and Kappa
• Central actions and peripheral actions
• Sedation in humans

Question 8

Peripheral Actions of Morphine (opiate): Cardiovascular system

Answer 8

-Mu receptor -> Bradycardia reduced preload and reduced dyspnea with pulmonary edema

Question 9

Peripheral Actions of Morphine (opiate): Mast cells

Answer 9

-Histamine release from Mast Cells -> Transient hypotension and pruritus

Question 10

Peripheral Actions of Morphine (opiate): GI tract

Answer 10

-Constipation, increased resting tone, decreased propulsive movement

Question 11

Peripheral Actions of Morphine (opiate): Brain Biliary Urinary Lungs

Answer 11

• Decreased breathing rate -> increased pCO2 -> brain vessels dilate -> increase in intracerebral pressure
• Biliary tract spasm
• Urethral and Ureter spams
• Urinary retention

Question 12

Morphine (opiate) respiratory suppression:

Answer 12

1st. ) Upper voluntary respiratory centers blocked
2nd. ) CO2 drive suppressed
3rd. ) O2 drive suppressed

Question 13

Why do you not give oxygen to a patient with morphine O2 drive suppression?

Answer 13

The only reason they continue to breath is due to the oxygen drive, if you give them oxygen they will stop breathing on their own

Question 14

What reverses the reduced preload and after load due to narcotics?

Answer 14

Naloxone -> Mu receptor inverse agonist (binds to the Mu receptor but instead of activating it, it causes the complete opposite reaction than normal agonists)

Question 15

Narcotics to treat diarrhea:

Answer 15

• Loperamide

- Diphenoxylate

Question 16

Loperamide:

Answer 16

• Diarrhea treatment
• Does not achieve significant CNS levels
• Only exposure is in the GI tract

Question 17

Diphenoxylate:

Answer 17

• Diarrhea treatment
• Contains atropine
• Atropine makes you sick to reduce addiction or abuse

Question 18

Narcotic Analgesic Groups:

Answer 18

• Morphine-like
• Methadone
• Phenylpiperidines (most effective)

Question 19

Morphine-Like Structure Drugs: Opiates

Answer 19

• Morphine
• Hydromorphine
• Oxomorphone
• Codeine
• Hydrocodone
• Oxycodone

Question 20

Tincture Opiates:

Answer 20

• Laudanum (stonger)

- Paregoric

Question 21

Hydromorphone:

Answer 21

Stronger than morphine

Question 22

Oxycodone/Hydrocodone:

Answer 22

More potent than morphine and longer half-life

Question 23

Codeine:

Answer 23

• Less potent than morphine

- Body converts codeine to morphine

Question 24

Morphine Metabolism:

Answer 24

First pass of liver

Question 25

Methadone-like drugs: opiods

Answer 25

- Methadone | - Diphenoxylate

Question 26

Methadone:

Answer 26

- Slower progression of tolerance | - Less severe immediate physical withdrawal symptoms

Question 27

Diphenoxylate:

Answer 27

- Contains atropine | - Antidiarrheal

Question 28

Fentanyl-Like: Opiods

Answer 28

- Fentanyl - Remifentanil - Meperidine - Diphenoxylate - Loperamide

Question 29

Fentanyl:

Answer 29

Way more potent than morphine

Question 30

Remifentanil:

Answer 30

- Short acting drug | - Used Post-Surgery

Question 31

Meperidine:

Answer 31

- Anticholinergic - Can cause grand mal seizures - DRUG INTERACTIONS with MAO Inhibitors and SSRI

Question 32

Mixed Agonist-Antagonist Actions:

Answer 32

- Mixed narcotic agonists of kappa receptors - Partial narcotic agonists or antagonist of mu receptors - Not effective pain relievers and will precipitate withdrawal

Question 33

Mixed Agonist-Antagonist Use:

Answer 33

- Short term pain relief | - Not as much respiratory depression

Question 34

What are Mixed Agonist-Antagonists reversal resistant to?

Answer 34

Naloxone and other Mu-receptor antagonists bc they

Question 35

Morphine like Mixed agonist antagonists:

Answer 35

- Nalbuphine | - Buprenorphine

Question 36

Other Mixed agonist antagonists:

Answer 36

- Butorphanol | - Pentazocine

Question 37

Buprenorphine:

Answer 37

- Partial agonist at mu receptor | - Binds and unbinds slowly from mu receptor

Question 38

Nalbuphine:

Answer 38

- Less effect on respiratory depression - Precipitates acute withdrawal in physically dependent patients (mu antagonist) - Significant analgesia mediated through kappa receptor

Question 39

Tramadol:

Answer 39

- Weak mu receptor agonist | - Inhibits reuptake of serotonin and norepinephrine in the braine

Question 40

Tapentadol:

Answer 40

- Weak mu agonist | - Inhibits reuptake of norepinephrine in the brain

Question 41

Antitussives:

Answer 41

- Codeine - Dextromethorphan - Benzonatate

Question 42

Codeine:

Answer 42

- Mu mediated action | - NOT for children under 6

Question 43

Dextromethorphan:

Answer 43

- Weak mu agonist - NOT for children under 6 - NOT combined with SSRI or MAO - NMDA receptor agonist -> Dysphoria and Seizures - NOT NALOXONE reversible

Question 44

Benzonatate:

Answer 44

- Not an Opiate - Local anesthetic - NOT for children under 6

Question 45

Treatment as antitussive for children under 6:

Answer 45

Teaspoon of honey

Question 46

Pure Mu Receptor Narcotic Antagonists:

Answer 46

- Naloxone - Naltrexone - Methylnaltrexone - Alvimopan

Question 47

Naloxone:

Answer 47

Short acting

Question 48

Naltrexone:

Answer 48

- Long acting | - Used for long term treatment of narcotic nicotine and ETOH dependence

Question 49

Methylnaltrexone and Alvimopan:

Answer 49

- Used for mu receptor mediated constipation | - Dose not pass BBB so it does not affect analgesic affects in the brain

Question 50

Narcotic withdrawal symptoms:

Answer 50

- Complete opposite of the initial effects of the drugs | - Urinary retention is the only symptom that occurs in withdrawal and initial drug use

Question 51

Tolerance:

Answer 51

- Initially regulated by G protein -> deactivate opioid receptors, Arrestin activation - Later on is alteration of neurotransmitters