Opioids: MOA

Question 1

Dextromethorphan

Answer 1

active at the dextramethorphan receptors –> cough relief

also possibly antagonist at NMDA receptor

Question 2

Naloxone

Answer 2

MOR antagonist

Question 3

Pentazocine

Answer 3

KOR agonist and MOR antagonist

good for analgesia at spinal and supra-spinal sites

Question 4

Buprenorphine

Answer 4

same MOA as morphine but PARTIAL agonist

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 5

Morphine (detailed)

Answer 5

full MOR agonist

spinal effect:
activates MOR at terminal end of C-fibers at dorsal horn –> inhibition of Ca/Na channels –> inhibition of depol –> no NT release by C fibers –> inhibition of ascending pain pathway

supra-spinal effect:
activates MOR in PAG (brain) –> activation of descending pain inhibitory pathway –> release of enkephalins at dorsal horn –> hyperpolarization s/t efflux of K at ascending pain neurons –> inhibition of ascending pain pathway

Question 6

Hydromorphone

Answer 6

full MOR agonist like morphine

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 7

Methadone

Answer 7

full MOR agonist like morphine

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 8

Meperidine

Answer 8

full MOR agonist like morphine

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 9

Fentanyl

Answer 9

full MOR agonist like morphine but SHORT ACTING

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 10

Codeine

Answer 10

PRODRUG – has to be metab first by CYP2D6, then same as morphine (full MOR agonist)

RESISTANCE TO CODEINE EXISTS D/T GENETIC MUTATION

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn

Question 11

Hydrocodone and oxycodone

Answer 11

full MOR agonist like morphine

WEAK acting, but undergoes partial metab by CYP2D6 and friends to MORE ACTIVE metabolite

spinal effect: prevents depol of C fibers

supra-spinal effect: release enkephalins to hyperpol second order neurons at dorsal horn