Why Would You Use an Opioid Agonist-Antagonist?
Question by T: Why would you use an opioid agonist-antagonist?
I am currently taking a pharmacology course and my professor has yet to e-mail me back. I’m wondering why opioid agonist-antagonists (aka “partial agonists” or “mixed agonists”) are used rather than simply using low doses of opioid agonists?
I know that opioid agonist-antagonists have a “ceiling effect” so they are often given to opioid addicts and women in labor. Does the ceiling effect have something to do with why opioid agonist-antagonists are chosen over low doses of opioid agonists sometimes?
Thank you!
Tiffany
PS: I always choose a best answer. I won’t leave you guys in limbo, ha!
Best answer:
Answer by A
I used brupenorphine (Subutex, or Suboxone there in the US) to get off of heroin. It eased the withdrawals but also blocked the effects of heroin, making it completely pointless to buy some. That was eight years ago and I’ve been free of all opiates since then, this is something that another opiate like methadone could never have helped me to achieve, that stuff just made me more addicted than ever instead.
Edit: Good answer Jared. I hadn’t realised that Suboxone contained naloxone too, so far as I know only Subutex or methadone is prescribed here in the UK, well that was the situation back then anyway.
Answer by Jared
Great question Tiffany!
You have the crux of the primary reason(s) for opioid compounds with mixed antagonist and agonist properties already in your mind – from the prose of your question.
A, the first comment/answer — gave a good anecdotal personal story of his addiction and use of a very well known opiate agonist/antagonist (buprenorphine).
This, when combined with Naloxone (a PURE opiate antagonist at all receptor sites) is referred to as Suboxone. The buprenorphine’s brand name in the US is called “Subutex”. Thus, Combining Subutex with the opioid antagonist Naloxone resulted in the naming of “Suboxone” — just for clarification.
That said,.. in *some* cases JUST Subutex, (pure buprenorphine) is used for opiate addiction (and even pain control in some less common cases). The reasons are varied, but buprenorphine is still, without the naloxone adjunct , an opioid antagonist and agonist. Thus it has properties of a ceiling effect for the analgesia, and CNS effects of opiate/opioid agonist effects.
Buprenorphine is a very potent partial agonist at the mu-receptor (a primary receptor for analgesia and the desired receptor of choice for common opioid painkillers) — to put it in perspective Intramuscular injection of buprenorphine is 30 times more potent than morphine. (Given morphine is the gold standard of comparison for opioid/opiate efficacy.)
That said, Buprenorphine has a ceiling effect (as you alluded to) generally 16mg (sublingual) for example is about the ceiling in a 24hour period (though with each individuals physiology anecdotal reports can vary) — This particular drug is most commonly used for addiction treatment to opioids and is often given in 2mg increments – though this is going beyond the scope of your question.
The primary reason(s) to use opioid agonist/antagonists OVER pure opioid agonists is to reduce the potential CNS effects of the parent drug — With agonist/antagonists , by their very nature of receptor binding and and removal, — reduce the amount of possible respiratory depression. (Which is a primary concern for opioid/opiate lethality.)
So taking this example – in a woman during labor this would be a beneficial choice of analgesic for childbirth in which the patient may not have ANY tolerance to opiates,.. further to not cause any preventible complications such as CNS respiratory depression during child birth/labor. (In short, it would be a safer choice.) All of that stated, it is still quite common to use pure opioid agonists in small monitored dosages because we are still much more familiar with their action and conversions than the agonist/antagonist variety.
The ceiling effect PRIMARILY allows for the abuse potential to be lower because ANY Opioid (agonist or mixed) will give some side effect of ‘euphoria’ at least initially until tolerance and brain adaptation (receptor neuroplasticity) have occurred. Thus, again using the Suboxone (buprenorphine/naloxone) example a patient who is an addict won’t be inclined to take say, double their daily dose in an effort to get ‘high’ or increase effect. They may try,.. and due to all the aforementioned effects they will not be putting themselves in any danger by doing so — and will quickly realize more does NOT equal (high/higher).
Since you are studying pharmacology – I thought I would clarify the Naloxone added to the Buprenorphine is not for active effect when taken orally (sublingually) — the naloxone does not enter the brain/cns when taken properly — however, if one decides (as some addicts may do) to inject their oral/sublingual suboxone they will have the naloxone become active and it will , as it is a pure opioid antagonist, knock all the opioids in the brain from their respective receptor sites — leaving the person in acute precipitated withdrawal.
You may ask why include a drug that has no ‘value’ unless injected (misused) — well this is due to buprenorphine being MANY times more potent when injected (I.V.) verses oral/sublingual use.
Which is why in addicts Suboxone (Buprenorphine + Naloxone) is immensely preferred over Buprenorphine alone.
Lastly – opioid agonist/antagonist mixed medications (ie: nalbuphine) give “moderate” analgesia while limiting the typical side effect profile of pure agonist opioids. Limiting: pruritis, nausea/emisis, constipation, urinary retention, respiratory depression, excessive sedation, etc.
Hope that helps,