Opioids, Opioid Substitutes, Opioid Antagonists

OPIOID AGONISTS

* Morphine
* Methadone
* Fentanyl
* Codeine
* Hydrocodone

MIXED OPIOID AGONIST­ANTAGONISTS

* Buprenorphine
* Nalbuphine

ANTITUSSIVES

* Dextromethorphan

OPIOID ANTAGONISTS

* Naloxone

OTHER ANALGESICS USED IN MODERATE PAIN

* Tapentadol
* Tramadol

OPIOID AGONISTS (Additional)

* Hydromorphone, oxymorphone: Like morphine in efficacy, but higher potency
* Meperidine: Strong agonist with anticholinergic effects
* Oxycodone: Dose­dependent analgesia
* Sufentanil, alfentanil, remifentanil: Like fentanyl but shorter durations of action
* Carfentanil: Like fentanyl but much more potent

OPIOID ANTAGONISTS (Additional)

* 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 weight­loss programs
* Alvimopan, methylnaltrexone bromide, naldemedine: Potent µ antagonists with poor entry into the central nervous system; can be used to treat severe opioid­induced constipation without precipitating an abstinence syndrome

MOA: Morphine, Methadone, Fentanyl

* Strong µ­ receptor agonists
* variable affinity for δ and κ receptors

Effects: Morphine, Methadone, Fentanyl

* Analgesia
* relief of anxiety
* sedation
* slowed gastrointestinal transit

Clin App: Morphine, Methadone, Fentanyl

* Severe pain
* adjunct in anesthesia (fentanyl, morphine)
* pulmonary edema (morphine only)
* maintenance in rehabilitation programs (methadone only)

PIT: Morphine, Methadone, Fentanyl

* First­pass effect
* duration 1–4 h except methadone, 4–6 h
* Toxicity: Respiratory depression
* severe constipation
* addiction liability
* convulsions

MOA: Codeine, Hydrocodone

* Less efficacious than morphine
* can antagonize strong agonists

Effects: Codeine, Hydrocodone

* Like strong agonists
* weaker effects

Clin App: Codeine, Hydrocodone

* Mild­moderate pain
* cough (codeine)

PIT: Codeine, Hydrocodone

* Like strong agonists, toxicity dependent on genetic variation of metabolism

MOA: Buprenorphine

* Partial µ agonist
* κ antagonist

Effects: Buprenorphine

* Like strong agonists but can antagonize their effects
* also reduces craving for alcohol

Clin App: Buprenorphine

* Moderate pain
* some maintenance rehabilitation programs

PIT: Buprenorphine

* Long duration of action 4–8 h
* may precipitate abstinence syndrome

MOA: Nalbuphine

* κ Agonist
* µ antagonist

Effects: Nalbuphine

* Similar to buprenorphine

Clin App: Nalbuphine

* Moderate pain

PIT: Nalbuphine

* Like buprenorphine

MOA: Dextromethorphan

* Poorly understood but strong and partial µ agonists are also effective antitussives

Effects: Dextromethorphan

* Reduces cough reflex
* dextromethorphan, levopropoxyphene not analgesic

Clin App: Dextromethorphan

* Acute debilitating cough

**PIT**: Dextromethorphan

* Duration 30–60 min
* Toxicity: Minimal when taken as directed

MOA: Naloxone

* Antagonist at µ, δ, and κ receptors

Effects: Naloxone

* Rapidly antagonizes all opioid effects

Clin App: Naloxone

* Opioid overdose

**PIT**: Naloxone

* Duration 1–2 h (may have to be repeated when treating overdose)
* Toxicity: Precipitates abstinence syndrome in dependent users

MOA: Tapentadol

* Moderate µ agonist, strong NET inhibitor

Effects: Tapentadol

* Analgesia

Clin App: Tapentadol

* Moderate pain

**PIT**: Tapentadol

* Duration 4–6 h
* Toxicity: Headache; nausea and vomiting; possible dependence

MOA: Tramadol

* Mixed effects: weak µ agonist, moderate SERT inhibitor, weak NET inhibitor

Effects: Tramadol

* Analgesia

Clin App: Tramadol

* Moderate pain
* adjunct to opioids in chronic pain syndromes

PIT: Tramadol

* Duration 4–6 h
* Toxicity: Seizures
* risk of serotonin syndrome