Chemistry of opioids and opioid antagonists 2

Hydromorphone

Dilaudid, Exalgo

4-7.5x potency of morphine

less incidence of OIP

R = H

Hydrocodone

Zohydro, Hysingla

active itself

antitussive activity

6-8x potency of morphine

R = CH3

Oxymorphone

Opana

10x potency of morphine

R = H

Oxycodone

Roxicodone, OxyContin

1.5-2x potency of morphine

active itself

R = CH3

Naloxone

pure opioid antagonist

t ½ plasma = 30-81 min

Tx opioid OD

orally ineffective (1st pass effect, glucuronidation)

Narcan, Evzio, Zimhi

nasal spray, auto-injectable, injection

Naloxegol

Movantik

PAMORA - pgp substrate
Tx OIC

PEG polymer

GI effects of opioids

inhibition of GI propulsion

increase in GI tone

inhibition of GI secretion

OIC (opioid-induced constipation)

hard dry stool

bloating

straining

infrequent/incomplete defecation

sequels/secondary symptoms of OIC

gastro-esophageal reflux

nausea and vomiting

anorexia

abdominal distention

abdominal cramping

interference with digestion

interference with drug absorption

Naltrexone

antagonist - more potent than naloxone

orally active

DOA = 4h

maintenance Tx of OUD

Tx alcohol dependence

Naltrexone metabolism: AKR

forms 6 beta-naltrexol

Bupropion

antidepressant, decreases reuptake of NE, DA

side effect - weight loss

in a combo drug with Naltrexone for Tx obesity

Methylnaltrexone

Relistor

soln for injection, oral tablet

PAMORA (Tx OIC)

Nalmefene

soln for injection

nasal spray, auto-injector

Tx opioid OD, alcohol dependence

naldemedine

Symproic

Tx OIC

Lybalvi

Olanzapine (antipsychotic) + Samidorphan L-malate

olanzipine - causes massive weight gain

Sami - mitigates weight gain