~Teachingcenter的醫學筆記~

鴉片類藥物整理
Opioids, Opioid Substitutes, and Opioid Antagonists

Strong opioid agonists

1. Agents
   • Morphine
   • Methadone
   • 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
2. Mechanism of action
   • Strong μ-receptor agonists.
   • Variable affinity for δ and κ receptors.
3. Effects
   • Analgesia.
   • Relief of anxiety.
   • Sedation.
   • Slowed gastrointestinal transit.
4. Clinical applications
   • Sever pain.
   • Adjunct in anesthesia (fentanyl, morphine).
   • Pulmonary edema (morphine only).
   • Maintenance in rehabilitation programs (methadone only).
5. Pharmacokinetics, toxicities, interactions
   • First-pass effect.
   • Duration 1~4 hours except methadone (4~6 hours).
   • Toxicity
     1. Respiratory depression.
     2. Severe constipation.
     3. Addiction liability.
     4. Convulsions.

Partial agonists

1. Agents
   • Codeine
   • Hydrocodone
2. Mechanism of action
   • Less efficacious than morphine.
   • Can antagonize strong antagonists.
3. Effects
   • Like strong agonists.
   • Weaker effects.
4. Clinical applications
   • Mild-moderate pain.
   • Cough (codeine).
5. Pharmacokinetics, toxicities, interactions
   • Like strong agonists.
   • Toxicity: dependent on genetic variation of metabolism.

Mixed opioid agonist-antagonists

1. Agents
   • Buprenorphine
   • Nalbuphine
2. Mechanism of action
   • Buprenorphine
     1. Partial μ agonist.
     2. Mixed with κ antagonist.
   • Nalbuphine
     1. Mainly κ agonist.
     2. Mixed with μ antagonist.
3. Effects
   • Like strong agonists but can antagonize their effects.
   • Also reduces craving for alcohol.
4. Clinical applications
   • Buprenorphine
     1. Moderate pain.
     2. Some maintenance rehabilitation programs.
   • Nalbuphine: moderate pain.
5. Pharmacokinetics, toxicities, interactions
   • Long duration of action 4~8 hours.
   • May precipitate abstinence syndrome (= withdrawal syndrome).

Antitussives

1. Agents
   • Dextromethorphan
   • Codeine, levopropoxyphene: like dextromethorphan
2. Mechanism of action
   • Poorly understood but strong and partial μ agonists are also effective antitussives.
3. Effects
   • Reduces cough reflex.
4. Clinical applications
   • Acute debilitating cough.
5. Pharmacokinetics, toxicities, interactions
   • 30~60 min duration.
   • Toxicity: minimal when taken as directed by physician.

Opioid antagonists

1. Agents
   • Naloxone
   • Naltrexone, nalmefene: like naloxone but longer durations of action (10+ hours)
     1. Naltrexone is used in maintenance programs and can block heroin effects for up to 48 hours.
     2. Naltrexone is also used for alcohol and nicotine dependence.
     3. When combined with bupropion, may be effective in weight loss programs.
   • Alvimopan, methylnaltrexone bromide: potent μ antagonists with poor entry into the central nervous system, can be used to treat severe opioid-induced constipation without precipitating on abstinence syndrome (= withdrawal syndrome).
2. Mechanism of action
   • Antagonist at μ, δ, and κ receptors.
3. Effects
   • Rapidly antagonizes all opioid effects.
4. Clinical applications
   • Opioid overdose.
5. Pharmacokinetics, toxicities, interactions
   • Duration 1~2 hours (may have to be repeated when treating overdose).
   • Toxicity: precipitates abstinence syndrome in dependent users.

Other analgesics used in moderate pain

1. Agents
   • Tapentadol
   • Tramadol
2. Mechanism of action
   • Tapentadol
     1. Moderate μ agonist
     2. Strong norepinephrine transporter (NET) inhibitor.
   • Tramadol
     1. Weak μ agonist.
     2. Moderate serotonin reuptake transporter (SERT) inhibitor.
     3. Weak NET inhibitor.
3. Effects
   • Analgesia.
4. Clinical applications
   • Tapentadol: moderate pain.
   • Tramadol
     1. Moderate pain.
     2. Adjunct to opioids in chronic pain syndromes.
5. Pharmacokinetics, toxicities, interactions
   • Tapentadol
     1. Duration 4~6 hours.
     2. Toxicity: headache, nausea, and vomiting, possible dependence.
   • Tramadol
     1. Duration 4~6 hours
     2. Toxicity: seizures and risk of serotonin syndrome ().

※ Serotonin syndrome

1. Cognitive effects: headache, agitation, hypomania, mental confusion, hallucinations, coma
2. Autonomic effects: shivering, sweating, hyperthermia, vasoconstriction, tachycardia, nausea, diarrhea.
3. Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor.