Opioid antagonists

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Opioid antagonists

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USMLE® Step 2 style questions USMLE

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A 65-year-old woman is diagnosed with metastatic breast cancer and started on high-dose oxycodone to manage severe bone pain. Two weeks later, the patient returns to the office because of increasingly hard, small volume, and difficult to pass stools with associated bloating. She has tried a high fiber diet, polyethylene glycol, and bisacodyl without significant symptomatic improvement. However, she has experienced significant improvement in bone pain. Vitals are within normal limits. Physical examination shows a mildly distended abdomen and decreased bowel sounds. Which of the following µ-receptor antagonists can be used to help in the management of this patient’s symptoms without precipitating symptoms of opioid withdrawal?  

External References

First Aid

2024

2023

2022

2021

Naloxone

dextromethorphan overdose p. 705

heroin detoxification p. 594

for opioid toxicity p. 247, 567, 588

Transcript

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Opioid antagonists, like the name suggests, are medications used mainly to reverse the side effects of opioid agonists and to prevent opioid addicts from relapsing after they’ve recovered.

Now, all opioids work by binding to opioid receptors in the brain, spinal cord, and gastrointestinal tract.

Some are endogenous, meaning they are produced naturally by the body, like endorphin, short for endogenous morphine.

But others are exogenous, meaning they come from outside the body, like heroin and morphine, which come from the opium poppy; a flowering plant that oozes a milky white liquid.

To understand how opioids work, let’s zoom into a region of the brain tissue that has opioid receptors.

Normally, in the absence of endorphins, inhibitory neurons secrete a neurotransmitter called gamma-aminobutyric acid, or GABA, that prevents nearby neurons from releasing neurotransmitters like dopamine, serotonin, and norepinephrine.

Now, let’s say someone goes to play a rigorous game of badminton. Exercise releases endorphins which activate the three major opioid receptors located on the inhibitory neurons, called the mu, kappa, and delta receptors.

As endorphins bind to these receptors, they block the inhibitory neuron from releasing GABA, allowing the dopamine, serotonin, and norepinephrine secreting neurons to freely unload their neurotransmitters, which then gets picked up by another neuron in the same area.

Norepinephrine and serotonin release takes place in pain processing regions of the brain like the thalamus, brainstem, and spinal cord, resulting in a decreased sensitivity to pain.

When dopamine release takes place in reward pathway regions like the ventral tegmental area, nucleus accumbens, and prefrontal cortex, the result is a calming sensation that feels really good.

Summary

Opioid antagonists are drugs that strongly bind to opioid receptors and prevent their activation. They are used to treat opioid overdose and addiction, and can also help to reverse respiratory depression and other adverse effects of opioids. Examples include drugs like naloxone, naltrexone, methylnaltrexone, and alvimopan.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Naloxone treatment in opioid addiction: the risks and benefits" Expert Opin Drug Saf (2007)
  5. "Methylnaltrexone" Drugs (2010)
  6. "Naltrexone: A Pan-Addiction Treatment?" CNS Drugs (2016)
  7. "Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting" The American Journal of Emergency Medicine (2019)