9. Pharm: Opioids

Question 1

What are the most common drugs involved in prescription opioid OD deaths?

Answer 1

1. Methadone
2. Oxycodone
3. Hydrocodone

Question 2

Who is more likely to OD on opioids?

Answer 2

1. 25 - 54 YO
2. M
3. Whites & American-Indian or Alaskan Natives

Question 3

Opioid AGO (9)

Answer 3

1. Morphine
2. Hydromorphine
3. Methadone
4. Oxycodone
5. Hydrocodone
6. Fentanyl
7. Codeine
8. Propoxyphene
9. Meperidine

Question 4

Opioid Partial AGO (Mixed AGO/ANT)

Answer 4

1. Buprenorphine
2. Nalbuphine
3. Butorphanol
4. Pentazocine

Question 5

Opioid ANT

Answer 5

1. Naloxone
2. Naltrexone

Question 6

General MOA of opioid analgesics

Answer 6

1. Binds to opioid receptor in the CNS: close presynaptic Ca2+ channels; open post-synpatic K+ channel => ↓ synaptic transmission => inhibit release of ACh, NE, 5HT, glutamate and substance P
   
   1. Inhibiting ascending pain pathways
   2. Decrease response and pain perception (nociception)
   3. CNS depression

Question 7

What is the general onset of action of opioid drugs?

Answer 7

• Depends on the patient: dosing must be individualized
  
  • Oral (immediate release) => work in 30 minutes
  • IV => work in 5 - 10 minutes

Question 8

What is the general duration of pain relief of

• 1. Immediate release opioids (tablet, oral solution or injection)
• 2. Extended release capsule and tablet
• 3. Epidural or intrathecal
• 4. Suppository

Answer 8

1. 3- 5 hours
2. 8 - 24 hours
3. 1 dose lasts up to 24 hours
4. 3 -7 hours

Question 9

Black Box Warning for Opioids

Answer 9

• Can cause respiratory depression: watch closely, especially when initiating or increasing dose.
  
  • CO2 retention from opioid-induced respiratory depression can worsen sedating effects of opiods.

Question 10

Opioid AE

Answer 10

1. CNS depression
2. Constipation: problematic in ppl with [unstable angine or post-MI], so consider preventative measures to decrease possib of constiptation (stool softner or fiber)
3. HypOtension: can cause severe hypOtension (including orthostatic hypotension and syncope); use with caution in ppl with
   
   1. hypovolemia/shock
   2. CV disease
   3. Drugs that worsen hypotensive effects (phenothiasinzes or general anesthetics)

Question 11

What opioid is the most potent?

Answer 11

fentanyl > buprenorphine

Question 12

Indications for Opioids

Answer 12

Manage pain and acute/chronic pain in patients with

1. MI
2. Sickle cell crisis
3. Post-op
4. Trauma/cancer
5. Back pain
6. Kidney stones
7. General anesthesia/epidural anesthesia
8. Palliative care
9. Antitussive
10. Anti-diarrheal (Loperamide)

Question 13

Types of opioid receptors

Answer 13

1. Mu (u)

2. Delta

3. Kappa

Question 14

Mu receptors respond best to what endogenous opioid peptides?

Answer 14

endorphins > enkaphalins > dysnorphins

Question 15

Delta receptors respond best to what endogenous opioid peptides?

Answer 15

Enkephalins > [endorphins and dysnorphins]

Question 16

Kappa receptors respond best to what endogenous opioid peptides?

Answer 16

Dysnorphins >>> endorphins and enkephalins

Question 17

MOA of Methadone

Answer 17

Mu opiod receptor full AGO

Treats: opioid addiction

Question 18

MOA of Buprenorphine

Answer 18

Mu, kappa and delta partial AGO.

Treats: opioid addiction

Question 19

MOA of Naltrexone

Answer 19

Mu-R ANT and kappa partial AGO.

Treat: alcohol and opioid addiction

Question 20

MOA of Nalmefene

Answer 20

Mu-R ANT and Kappa-R partial AGO.

Treat: alcohol addiction

Question 21

High degree of tolerance may develop to what effects of opioids?

Answer 21

1. Analgesia
2. Euphoria, dysphoria
3. Mental clouding
4. Sedation
5. Respiratory depression
6. Antidiuresis/N/V
7. Cough suppression

Question 22

Moderate degree of tolerance may develop to what effects of opioids?

Answer 22

1. Bradycardia

Question 23

Minimal/no degree of tolerance may develop to what effects of opioids?

Answer 23

1. Miosis
2. Constipation
3. Convulsions

Question 24

AE of Chronic Opioid Use

Answer 24

1. Hypogonadism
2. Immunosupression
3. Increased feeding
4. Withdrawal, tolerance/dependence
5. Abuse/addiction
6. Hyperalgesia

Question 25

**Opioid** Drug Interactions

Answer 25

1. **Sedative-Hyponotics:** ↑ CNS depressions (resp depression) 2. **Antipsychotic agents:** ↑ sedation, worsen CV effects (antimuscarinic and a-blocking actions) 3. **MAO-I:** relative CI to all opioids d/t ↑ incidence of _hyperpyrexic coma_

Question 26

**_Morphine Sulfate_** 1. Indication 2. CI 3. Warnings and precautions\*\*\* 4. Adverse reactions\*\*\*

Answer 26

1. **Opioid AGO** used to manage pain that does _NOT_ respond to non-narcotic analgesics 2. **CI**: 1. Hypersensitive/allergy to morphine; 2. Bronchial asthma or UA obstruction, respiratory depression WO resuscitative equipment 3. **Warnings and precautions** 1. Dosing errors: pay atn to confusion in dosing concentrations (mg vs m:) 2. Respiratory depression 3. CNS depressants: increase risk of resp depression 4. CNS toxicity 4. **AE:** 1. Sedation, lightheadedness/dizziness, N/V, constipation

Question 27

**_Buprenophine_** 1. Indication 2. Warnings and precautions 3. Drug interactions\*\*\*\*

Answer 27

1. **_Treat opioid addiction and preferred for induction_** 2. **Warnings and precautions** 1. Can be _abused_: monitor stability of pt 2. _Resp depression_ and death can occur, esp when taking via IV with benzos and CNS depressants 3. ​​**Drug interactions** 1. _Broken down in liver by CYP3A4: Monitor patients starting/ending CYP3A4 inhibitors/inducers to prevent over/underdosing_

Question 28

**_Naloxone_** 1. MOA 2. Indication 3. Warnings and precautions

Answer 28

1. **MOA**: **_Pure_ opioid competitive ANT** that displaces opioid receptor sites 2. **Indication**: _Opioid OD (suspected or known)_ 1. _Completely or partially reverses opioid depression_ (& respiratory depression) caused _by natural/synthetic opioid_s (propoxyphene, methadone, nalbuphine, butorphanol, pentazocine) 2. SUSPECTED/ known acute opioid OD 3. **Warnings and precaution:** 1. **​Acute opioid withdrawal:** giving nalaxone in chronic opioid users =\> release of catecholamines =\> _acute withdrawal_ or _unmask pain_

Question 29

**_Naltrexone_** * MOA * Indication * Warnings and precautions

Answer 29

* MOA * **_Pure Opioid blocker (_mu competitive ANT),** with highest affinity for **mu receptors.** * **​****Indication:** * **​1. Alcohol use disorder:** prevents intoxication, euphoria and cravings * **2. Opioid dependence:** blocks effects of exogenous opioids; must withdraw first * Warnings and precaustions 1. **Accidental opioid overdose:** _respond to lower opioid doses than before_ =\> life-threatening opioid intoxication 2. **Acute opioid withdrawal:** cause withdrawal in pts dependent on opioids: pain, HTN, sweating, agitiation and withdrwaral; in neonates: _shrill cry, failure to feed._

Question 30

**Addicts** who cant get opioids OD on what? Treatment for OD?

Answer 30

* **Diarrhea drugs (Loperamide)** =\> tx diarrhea adn decrease drainage in ps with ostomies. Safe at recommeded doses. * **Tx for OD** = Naloxone: monitor vitals for at least 24 hours after last dose.