Opioid analgesics
Mechanism
- Agonists at opioid receptors (μ=β-endorphin, δ=enkephalin, κ=dynorphin) that modulate synaptic transmission by closing presynaptic Ca²⁺ channels and opening postsynaptic K⁺ channels → reducing synaptic transmission. Inhibit release of ACh, norepinephrine, 5‑HT, glutamate, substance P.
Efficacy
- Full agonists: morphine, meperidine (long‑acting), methadone, codeine (prodrug; activated by CYP2D6), fentanyl.
- Partial agonist: buprenorphine.
- Mixed agonist/antagonists: butorphanol, nalbuphine.
- Antagonists: naloxone, naltrexone, methylnaltrexone.
Clinical use
- Moderate to severe or refractory pain; diarrhea (loperamide, diphenoxylate); acute pulmonary edema; maintenance therapy in opioid use disorder (methadone, buprenorphine + naloxone); neonatal abstinence syndrome (methadone, morphine).
Adverse effects
- Nausea, vomiting, pruritus (histamine release), opioid use disorder, respiratory depression, constipation, sphincter of Oddi spasm, miosis (except meperidine → mydriasis), additive CNS depression with other drugs; tolerance does not develop to miosis or constipation; treat toxicity with naloxone, relapse prevention with naltrexone after detoxification.
Tramadol
Mechanism
- Very weak opioid agonist that also inhibits reuptake of norepinephrine and serotonin.
Clinical use
- Chronic pain
Adverse effects
- Similar to other opioids; lowers seizure threshold; risk of serotonin syndrome.
Fentanyl
Indication
- Preoperative analgesia
- Anaesthesia adjunct
- Regional anaesthesia adjunct
- General anaesthesia
- Postoperative pain control
- Moderate to severe acute pain (off-label)
Mechanism of action
- Mu-selective opioid agonist
- Capability to activate other opioid system receptors such as the delta and potentially the kappa-receptors
- Neurotransmitter dopamine (Da) is increased in the reward areas of the brain
- Causes addiction to the drug
- Fentanyl decreases cerebral blood flow
Pharmacokinetics
- Hepatically metabolized via the CYP450 enzyme system
- Half-life of 3 to 7 hours.
- Excretion
- 75% in the urine
- 9% in faeces
CI
- After operative interventions in the biliary tract, these may slow hepatic elimination of the drug.
- Respiratory depression or obstructive airway diseases (i.e., asthma, COPD, obstructive sleep apnoea, obesity hyperventilation, also known as, Pickwickian syndrome)
- Liver failure
- Known intolerance to fentanyl or other morphine-like drugs, including codeine, or any components in the formulation
- Known hypersensitivity (i.e., anaphylaxis) or any common drug delivery excipients (i.e., sodium chloride, sodium hydroxide).
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