Opioid antagonists

Definitions & Key takeaways

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.

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Introduction0:00–0:39

Opioid antagonists like the name suggests are medications that block opioid receptors. They're used mainly to urgently reverse the side effects of opioid agonists and to help individuals who are recovering from opioid use disorder.
Now, 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 endorphins named for endogenous morphine due to their similar effects on the body.
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.

Physiology0:39–1:51

Let's zoom in on a region of the spinal cord that has opioid receptors normally in the absence of endorphins. No susceptive fibers carry pain signals from the body to the dorsal or posterior horn of the spinal cord where they release neurotransmitters like glutamate substance P and calcitonin gene related peptide.
These neurotransmitters cause pain signals to be transmitted to the brain via ascending pain pathways. 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 neurons called the mu kappa and delta receptors.
As endorphins or other opioids bind to these receptors on the presynaptic terminals of nociceptive fibers. They inhibit the opening of calcium channels, preventing calcium influx and thereby blocking the release of pain causing neurotransmitters like glutamate substance P and calcitonin gene related peptide.
At the same time, endorphins also bind to postsynaptic neurons opening potassium channels here leading to hyperpolarization and decreased excitability of the neuron.

Pathology1:51–2:24

These effects together reduce the transmission of pain signals to the brain. Now, opioids also have action on the body's dopaminergic, noradrenergic and serotonergic pathways in the brain's reward pathway located in the midbrain opioids bind to receptors on inhibitory gabaergic neurons causing a decrease in the release of gamma Aminobutyric acid, also known as Gabaa.

Mechanism of action2:24–2:38

This in turn leads to less inhibition of dopaminergic neurons and therefore more dopamine. This increase in dopamine is why opioids cause feelings of pleasure or euphoria.

Naloxone2:38–3:53

For the noradrenergic effects, opioids inhibit noradrenergic neurons in the brain, especially in the locus ceruleus leading to a decrease in norepinephrine release.
This contributes to the sedative effects of opioids. Last certain opioids activate neurons that release serotonin in the spinal cord helping to reduce pain transmission.
Now that we've covered how opioids work. Let's talk more about some of the unwanted effects.
There are opioid receptors throughout our body like in the gastrointestinal tract. So, when a person receives a dose of morphine, it could also result in a series of unwanted side effects like nausea, vomiting and constipation.
Other side effects of opioids include pupillary constriction as well as flushing. However, the most dangerous side effect is respiratory depression caused by decreased activity in the medulla.
The part of the brain that regulates breathing. This happens when a person overdoses on an opioid, like morphine, fentaNYL or heroin.
Respiratory depression can be life threatening and should be treated right away because the person can literally stop breathing.

Naltrexone3:53–4:22

Also watch out for central nervous system depression, which can lead to coma and cardiac problems like bradycardia and other arrhythmias.
Now, in order to treat opioid overdoses, we can use an opioid antagonist like naloxone naltrexone. On the other hand, is a medication that is helpful as maintenance therapy and opioid use disorder and alcohol use disorder.

Methylnaltrexone4:22–4:42

Other opioid antagonists like methyl naltrexone and Alvimopan can help counteract opioid induced constipation. These medications all bind strongly to opioid receptors without activating them.
Since naloxone has a higher affinity for opioid receptors than opioid agonists like morphine, fentaNYL and heroin do. It actually displaces the agonist from the receptor and doesn't allow another to bind naloxone readily crosses the blood brain barrier and has a rapid onset and short duration of action of 1 to 2 hours.

Memory palace4:42–6:01

So when it's given intravenously or intranasally, it can reverse the central effects of opioids within minutes, potentially saving a person's life.
Another potential use of naloxone is to detect when a person is physically dependent on opioids. Although not commonly done, this can sometimes be useful before starting a long acting medication like NALTREXONE to help manage opioid use disorder.
The idea is that the patient is given naloxone under medical supervision to see if withdrawal symptoms occur prior to starting the long acting NALTREXONE.
If an individual has developed a physical dependence on opioids, administration of naloxone will cause the onset of withdrawal symptoms such as sweating, pupillary dilation, rhinorrhea, nausea, vomiting, or diarrhea, dysphoric mood, myalgias and yawning.
In this case, the use of naltrexone should be delayed until the individual has been opioid free for a sufficient period of time with supportive care provided to manage withdrawal symptoms.

Review6:01–6:30

In the meantime, now, naltrexone is also a centrally acting opioid antagonist like naloxone, but it has a much longer duration of action lasting from 24 to 48 hours.
This makes it useful in preventing relapse in people who recently recovered from an opioid use disorder because they no longer get a euphoric feeling even if they try to use opioids again.
Now, since alcohol can make people feel good by triggering the release of endogenous opioids like endorphins, naltrexone can also be helpful for people recovering from alcohol use disorder through the same mechanism.

Mind map6:30–9:36

The last group of opioid antagonists includes methylnaltrexone and alvimopan, which can't cross a blood brain barrier and are therefore said to be peripherally acting.
This means they can't be used to reverse central opioid effects like respiratory depression. But they are helpful to treat gi symptoms like constipation caused by opioid analgesics.
Alvimopan is particularly useful for treating postoperative ileus where there's decreased gi motility that's worsened by opioid use.
Methyl naltrexone is commonly used to treat opioid induced constipation in individuals on chronic opioid therapy. Now, let's make a simple and fun mnemonic that'll help you efficiently memorize these pharmacology facts since a lot of these medications have now in them, let's use a nail salon.
The right side of the salon is where we keep the medications that could cross the blood brain barrier. So let's put ATV showing the brain here.
Watching this show, we have a customer who's wearing a giant lock around her neck for naloxone. She's on a ventilator respirator to help you.
Remember, it's used to treat respiratory depression and the other side effects of opioid overdose. She's rather short to help you remember?
It's short acting. Now, waiting with her is a very tall lady in a tracksuit for the long acting Naltrexone.
She's adopting a more physically active lifestyle while recovering from substance use disorder as can be seen by an alcohol bottle and a needle in the trash can next to her.
This will help you remember, NALTREXONE is used to help people abstain from future substance use. Ok.
So on the left side of the room, we have the medications that don't cross the blood brain barrier, the TV, on this side is showing intestines to help you.
Remember, these are used for the gi side effects caused by opioid analgesics. Here we have naloxone s cousin Methyl Naltrexone who's wearing a nerdy.
I love Math t-shirt. Her husband is an Elvis impersonator for Alvimopan and he's moping about having to come to the nail salon.
All right. As a quick recap, opioid antagonists are medications that strongly bind to opioid receptors and prevent their activation.
Naloxone is used to treat respiratory depression caused by opioid overdose and to detect when a person is opioid dependent naltrexone is used to help individuals recovering from opioid or alcohol use disorders maintain abstinence.
Finally, methyl naltrexone and Alvimopan are used to treat gi side effects like constipation caused by opioid analgesics.
But wait, there's more, here's a mind map with all the pneumonics from the video. Go ahead and pause the video so you can test yourself to see what you remember.
Stay tuned for the answers at the end.