27. Opioid analgesic drugs. Semisynthetic, synthetic opioids, opioid antagonists

Semisynthetic opioids

The most important semisynthetic opioids are dihydrocodeine, ethylmorphine, hydrocodone, oxycodone and heroin.

Heroin (diacetylmorphine) is a prodrug which is rapidly metabolised into morphine and 6-monoacetylmorphine (6-MAM), which are active. 6-MAM is more lipophilic than morphine and therefore enters the CNS more readily, causing a stronger euphoria. For this reason, heroin has more abuse potential than morphine. It is purely a drug of abuse and has no clinical use.

Dihydrocodeine and ethylmorphine are used similarly as codeine (for mild pain and as cough suppressants).

Oxycodone is used similarly to morphine.

Synthetic opioids

The most important synthetic opioids are fentanyl, alfentanil, loperamide, methadone and tramadol.

Fentanyl is 100x more potent than morphine, and more lipophilic. It’s mostly used to treat perioperative pain or chronic pain. For chronic pain it’s usually given as a transdermal patch. Fentanyl increases the rigidity of the chest wall, which can impair breathing. Muscle relaxants can help with this.

Alfentanil has similar potency as fentanyl, but shorter duration of action.

Loperamide is an opioid that doesn’t cross the blood-brain barrier, so it doesn’t cause any central effects like analgesia, respiratory depression or sedation. It’s used for the treatment of diarrhoea.

Methadone is a long-acting opioid used for chronic pain and for treating opioid addiction. Due to its long half-life the effect wears off slowly, making it ideal to prevent withdrawal symptoms.

Tramadol is a prodrug. It’s metabolized into an active metabolite which binds to µ receptors. This metabolite also inhibits monoamine uptake. Tramadol doesn’t cause respiratory depression.

Opioid antagonists

Naloxone is a short-acting µ, κ and δ opioid receptor antagonist. It’s used to treat opioid overdose, and rapidly reverses opioid-induce analgesia and respiratory depression. It induces withdrawal symptoms in opioid-dependent persons.

Naltrexone is a long-acting µ, κ and δ opioid receptor antagonist. It’s given to opioid addicts that are at risk for relapse, as naltrexone will block any opioid effects that would occur if the person relapses.

Peripherally acting opioid antagonists like methylnaltrexone don’t cross the blood-brain barrier, and only antagonize opioid effects in the periphery. They’re used to reverse opioid-induced constipation.


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3 thoughts on “27. Opioid analgesic drugs. Semisynthetic, synthetic opioids, opioid antagonists”

  1. I think it’s important to mention the classification from the lecture. The table with the weak and strong agonists.

    Because this way, you haven’t mentioned what the classification for morphine and codeine are.

    1. The last topic mentions that morphine is a strong agonist and codeine a weaker one. I don’t think the classification itself brings anything new to the table.

      1. But in the exam, if they ask you to name some strong agonists, they include both “natural” and semisynthetic.

        Just a thought, since the lecture mentioned there are 2 ways to classify opioids.

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