Basic &Clinical Pharmacology, 15e >Opioid Agonists &Antagonists
Bertram G. Katzung, Todd W. Vanderah+ SUMMARY Opioids, Opioid Substitutes, and Opioid Antagonists
Subclass, Drug
Mechanism of Action
Effects
Clinical Applications
Pharmacokinetics, Toxicities
OPIOID AGONISTS
• Morphine
• Methadone
Strong µ-receptor agonists • variable
affinity for δ and κ receptors
Severe pain • adjunct in anesthesia
(fentanyl, morphine) • pulmonary
edema (morphine only) • maintenance
in rehabilitation programs (methadone
only)
First-pass effect • duration 1–4 h
except methadone, 4–6 h • Toxicity:
Respiratory depression • severe
constipation • addiction liability •
convulsions
Like strong agonists • weaker effects
Mild-moderate pain • cough (codeine)
Like strong agonists, toxicity
dependent on genetic variation of
metabolism
Moderate pain • some maintenance
rehabilitation programs
Long duration of action 4–8 h • may
precipitate abstinence syndrome
Analgesia • relief of anxiety • sedation
• slowed gastrointestinal transit
• Fentanyl
• Hydromorphone, oxymorphone: Like morphine in efficacy, but higher potency
• Meperidine: Strong agonist with anticholinergic effects
• Oxycodone: Dose-dependent analgesia
• Sufentanil, alfentanil, remifentanil: Like fentanyl but shorter durations of action
• Carfentanil: Like fentanyl but much more potent
• Codeine
• Hydrocodone
Less efficacious than morphine • can
antagonize strong agonists
MIXED OPIOID AGONIST-ANTAGONISTS
• Buprenorphine
Partial µ agonist • κ antagonist
Like strong agonists but can
antagonize their effects • also reduces
craving for alcohol
• Nalbuphine
κ Agonist • µ antagonist
Similar to buprenorphine
Moderate pain
Like buprenorphine
Poorly understood but strong and
partial µ agonists are also effective
antitussives
Reduces cough reflex •
dextromethorphan, levopropoxyphene
not analgesic
Acute debilitating cough
Duration 30–60 min • Toxicity: Minimal
when taken as directed
Opioid overdose
Duration 1–2 h (may have to be
repeated when treating overdose) •
Toxicity: Precipitates abstinence
syndrome in dependent users
ANTITUSSIVES
• Dextromethorphan
• Codeine, levopropoxyphene: Similar to dextromethorphan in antitussive effect
OPIOID ANTAGONISTS
• Naloxone
Antagonist at µ, δ, and κ receptors
Rapidly antagonizes all opioid effects
• Naltrexone, nalmefene: Like naloxone but longer durations of action (10 h); naltrexone is used in maintenance programs and can block heroin effects for up to 48 h; naltrexone is also used for alcohol and
nicotine dependence; when combined with bupropion, may be effective in weight-loss programs
• Alvimopan, methylnaltrexone bromide, naldemedine: Potent µ antagonists with poor entry into the central nervous system; can be used to treat severe opioid-induced constipation without precipitating an
abstinence syndrome
OTHER ANALGESICS USED IN MODERATE PAIN
• Tapentadol
Moderate µ agonist, strong NET
inhibitor
Analgesia
Moderate pain
Duration 4–6 h • Toxicity: Headache;
nausea and vomiting; possible
dependence
• Tramadol
Mixed effects: weak µ agonist,
moderate SERT inhibitor, weak NET
inhibitor
Analgesia
Moderate pain • adjunct to opioids in
chronic pain syndromes
Duration 4–6 h • Toxicity: Seizures •
risk of serotonin syndrome
NET, norepinephrine reuptake transporter; SERT, serotonin reuptake transporter.
Date of download: 08/24/23 from AccessMedicine: accessmedicine.mhmedical.com, Copyright © McGraw Hill. All rights reserved.