Opioids

Question 1

Morphine

Answer 1

Full mu agonists

Use:
-Chronic pain (cancer) (PO, intrathecal, epidural)
-post-operative pain relief (IV, intrathecal, epidural)

PK:
-1st pass metabolism (PO)

AEs:
-histamine release from mast cells –> vasodilation, allergic symptoms (pruritus)

Question 2

Methadone

Answer 2

Full mu agonists

Use:
-Chronic pain
-Maintenance drug for opioid-dependent patients (methadone maintenance program)

PK:
-long half-life

Question 3

Fentanyl

Answer 3

Full mu agonists

Use:
-Induction agent in anesthesiology (IV)
-Chronic pain (transmucosal, transdermal)

Administration:
-transmucosal lozenge among many other formulations

Question 4

Codeine

Answer 4

Full mu agonists

Use:
-mild/moderate pain (ceiling effect on analgesic efficacy)

PK: codeine = prodrug
-analgesic activity is dependent upon conversion of codeine to morphine by CYP2D6
-10% of population have polymorphism in CYP2D6 –> makes codeine ineffective as an analgesic

Question 5

Buprenorphine

Answer 5

Partial mu agonists

Use:
-post-operative pain
-maintenance drug for opioid-dependent patients

PK:
-long half-life

**partial agonist/partial antagonist: acts as partial antagonist in the presence of a full agonist

Question 6

Naloxone

Answer 6

mu Antagonists

MOA:
-blocks all opioid receptors (mu, delta, kappa)

Use:
-opioid overdose

Administration:
-IM, IV, auto-injector

**EVZIO: naloxone autoinjector approved for emergency treatment of known/suspected opioid overdose

*very short half-life

Question 7

Naltrexone

Answer 7

MOA:
-blocks all opioid receptors (mu, delta, kappa)

Uses:
-opioid dependence (alcohol dependence)

Administration:
-PO

*very long half-life (prevents drug-seeking behavior/no reward pathway)

Question 8

Tramadol

Answer 8

MOA:
-weakly stimulate mu opioid receptors
-weakly inhibit NET and SERT

Uses:
-mild to moderate pain (PO)

Administration:
-risk of causing seizures in normal individuals; use with caution in patients with pre-existing seizure disorders or history of seizures

**avoid in patients with seizure risk or on antidepressants (acts on NET and SERT)

Question 9

Other Opioid Considerations

Answer 9

Interactions:
-CYP interactions; Codeine
-CNS depressants

Tolerance:
-Tolerance, as defined by either of the following:
-need for markedly increased amounts of the substance to achieve intoxication/desired effect
-markedly diminished effect with continued use of the same amount of substance
-Cross-tolerance between opioids
-Degree of tolerance differs between various effects
-minimal tolerance to miosis and constipation