opioid receptor agonist (narcotic)

Introduction

Any morphine-like compound, natural or synthetic, that stimulates opioid receptors producing bodily effects including pain relief, sedation, constipation, & respiratory depression.

Indications

• treatment of moderate-severe acute pain or chronic pain
  • maximum dose for chronic pain = 90 mg morphine QD
• cough

Contraindications

• avoid morphine in patients with renal failure
  • hydromorphone is an effective alternative if renal failure
    • reduce dose with liver failure
    • methadone 1/2life averages 25 hours
  • transdermal fentanyl safest opiate in renal failure & liver failure
    • use only in opioid-tolerant patients
• meperidine is not recommended due to increased risk for seizures
• tramadol has drug interactions with other serotoninergic agent
• methadone 1/2life averages 25 hours

Dosage

• rescue dose for breakthrough pain should be 10% of daily dose
• when switching opioids, lower the dose of the new opioid by at least 25-50% of the calculated equianalgesic dose to account for inter-patient variability in response to opioids
• opioids do not have ceiling of analgesic efficacy

Relative opioid receptor potency: (mg for equipotent effects) (also see reference)

drug	route	dose (mg)
morphine	IM, SC	10
morphine	PO	30
hydromorphone (Dilaudid)	IM, SC	1.5
hydromorphone (Dilaudid)	PO	7.5
oxymorphone (Numorphan)	IM, SC	1
oxymorphone (Numorphan)	PR	5
oxymorphone (Numorphan)	PO	10
levorphanol (Levo-Dromoran)	IM, SC	2
levorphanol (Levo-Dromoran)	PO	4
methadone (Dolophine)	IM	5
methadone (Dolophine)	PO	10
meperidine	IM, SC	75
meperidine	PO	300
fentanyl* (Sublimaze)	IM	0.1
hydrocodone (Hycodan)	PO	30
oxycodone (OxyContin)	PO	20
propoxyphene	PO	65
pentazocine (Talwin)	IM, SC	60
pentazocine (Talwin)	PO	180
nalbuphine (Nubain)	IM	10
butorphanol (Stadol)	IM	10
Antitussive/antidiarrheal doses:
diphenoxlate	PO	5
loperamide	PO	2
codeine	IM	60
codeine	PO	180

* see fentanyl for patch equivalent to oral morphine

Combination drugs containing opiate

Percodan, Percocet, Endocet: see oxycodone

Darvon, Darvocet: see propoxyphene

* coprescribing naloxone with opioids for chronic pain may diminish opioid-related emergency department visits

Pharmacokinetics

• metabolized by cyt P450
  • glucuronide metablites excreted in urine
• duration of action:
  • generally 4-6 hours
  • exceptions:
    • meperidine 3-5 hours
    • fentanyl 1-2 hours
• 1/2 lives more variable than duration of action
• accumulation of glucuronide metablites with renal failure or in elderly patients taking high doses of morphine for prolonged periods
• hydromorphone, fentanyl, methadone, buprenorphine, hydrocodone show minimal pharmacokinetic changes in patients with renal failure

Adverse effects

• sedation
  • level of arousal dose-dependent
  • tolerance develops within a few days
• supression of the hypothalamic-pituitary axis
  • decreased secretion of gonadotropins (LH, FSH)
    • hypogonadism (both genders), erectile dysfunction
    • central origin; down regulation of GnRH
  • decreased secretion of ACTH
    • suboptimal morning cortisol in as many as 10%
• nausea/vomiting (tolerance develops within a few days)
• constipation
  • prevention & treatment of constipation (all patients
  • stimulant laxative (senna, bisacodyl) with or without docusate
    • stool softener (dosusate) may not add benefit to senna
  • osmotic agent (polyethylene glycol, sorbitol, lactulose)
  • naldemedine, naloxegol, or naltrexone
    • methylnaltrexone may help relieve constipation in palliative care patients without negating analagesic effect of opioid
  • tolerance does NOT develop to constipating effects
• distal esophageal spasm resulting in esophagogastric outflow obstruction
• urinary retention
• respiratory depression (tolerance develops)
• higher risk for invasive pneumococcal infection
• hypotension
• hypothermia
• hyporeflexia
• pruritus, hives, flushing due to release of histamine from mast cells
• miosis (usually)
• true allergy uncommon, generally adverse effect
• opioid-induced hyperalgesia
  • worsening pain (hyperalgesia) despite increase in opioid dosage
  • cognitive slowing, hyperreflexia, myoclonus
• long-acting opioids prescribed for non-cancer pain associated with increased risk for all-cause mortality (RR=1.72) & cardiovascular mortality (RR=1.65)
• increased risk of major depression & anxiety & stress-related disorders
• sleep disordered breathing: central sleep apnea
  • 70% of patient on chronic opioid therapy

also see opioid overdose

also see abuse-deterrent opioid

* Boxed warnings:

• risks for abuse, addiction, and misuse
• immediate-release opioids q4-6 hours only for severe pain not relieved by alternative treatments
• treatment should not be stopped suddenly in patients who are physically dependent on the drugs
• pregnant women who chronically use opioids put their newborns at risk for neonatal opioid withdrawal syndrome

* evaluate for opiate abuse if indicated

* concurrent opioid prescriptions from multiple providers increases risk for opioid-related hospitalization

• drug adverse effects of opiates
• drug adverse effects of psychotropic agents
• drug adverse effects of sedatives

Drug interactions

• avoid coadministation of CNS depressants
• benzodiazepines should not be used in combination

• drug interaction(s) of benzodiazepine with opiates
• drug interaction(s) of antidepressant with opiates
• drug interaction(s) of Z-drugs with opiates
• drug interaction(s) of alcoholic beverage with opiates
• drug interaction(s) of pregabalin with opiates
• drug interaction(s) of gabapentin with opiates

Laboratory

• see ARUP consult

Complications

• children of parents who use prescription opioids are more likely to attempt suicide (0.37% vs 0.14%)
• also see opioid overdose

Management

• CDC's 2022 guidelines cover acute, subacute, & chronic pain
• at hospital discharge, inquire about existing opioids at home

Notes

• FDA advisory panel endorses mandatory training for clinicians who prescribe opiates
• DEA to reduce opioid manfacturing by 25% in 2017
• higher opioid prescribing at the county level associated with
  • higher proportion of non-Hispanic whites
  • more uninsured & Medicaid patients
  • lower education levels
  • higher unemployment
  • greater density of primary care physicians
  • higher incidence of diabetes, arthritis, & disability

More general terms

• receptor agonist
• analgesic (antalgic)
• sedative/hypnotic (tranquilizer)

More specific terms

• 6-monoacetylmorphine
• abuse-deterrent opioid
• alfentanil (Alfenta, ALF)
• butorphanol (Stadol, Stadol NS)
• carfentanil
• codeine
• diacetylmorphine (diamorphine, heroin)
• difelikefalin (Korsuva)
• difenoxin
• dihydrocodeine
• fentanyl (Sublimaze, Subsys, Fentanyl Oralet, Actiq, Fentora, Onsolis, Abstral, Lazanda)
• hydromorphone; dihydromorphinone (Dilaudid, Palladone)
• levorphanol (Levo-Dromoran)
• meperidine (Demerol, Isonipecaine, Chlorbycyclen, Centralgin)
• methadone (Dolophine, Methadose, Physeptone, Algolysin)
• metonitazene
• Mitragyna speciosa; kratom
• mixed opioid agonist-antagonist (analgesic narcotic partial-mixed agonist)
• morphine (morphine sulfate [MS], MS Contin, Roxanol, Oramorph SR, Kadian, Avinza, DepoDur, Duromorph)
• narcotic combination
• normeperidine (Norpethidine)
• normorphine; desmethylmorphine; demethylmorphine
• oliceridine (Olinvyk)
• opioid partial agonist
• oxycodone (Roxicodone, OxyContin, OxyIR, OxyFast, Oxecta, Xtampza ER)
• oxymorphone (Numorphan, Opana, Opana ER)
• propoxyphene (Darvon, Dolene, Proxagesic, Novopropoxyn)
• sufentanil (Sufenta,Dsuvia)
• tapentadol (Nucynta)
• thiafentanil oxalate (Thianil)
• tianeptine
• tramadol (Ultram)

Additional terms

• opioid maintenance therapy
• Opioid Overdose
• opioid receptor antagonist or narcotic antagonist

Component of

• narcotic combination

Patient information

opioid receptor agonist patient information