Oxygen and opiates

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Lara

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As a student I have been told that oxygen metabolizes opiates and reduces the half life of opiates which I found quite interesting and that when an opiate OD (post naloxone) has recovered having a normal GCS and no signs of respiratory depression it is good practice to administer oxygen routinely regardless of oxygen saturations. This is against our guidelines so I did a bit of research. However, doing my own literature search I cannot find any explanation for this. Has anyone else been told this? Can anyone direct me to any evidence to support this?
 
Never heard of that. Sounds like bs to me, but I could be wrong.

@Remi ?
 
Yeah... Never heard of it.
 
I mean you should always oxygenate/ventilate your overdoses due to respiratory depression, but I have never heard of O2 reducing the half life of an opiate. Chemistry wise I'm not even sure how it would work honestly, the math just doesn't work out... There are a lot of studies out there that discuss the harmful effects of excessive oxygenation if anything.
 
"As a student I have been told that oxygen metabolizes opiates and reduces the half life of opiates"

I could be wrong, and this is a bit over my head, but I don't think this is a good way to think about it. It seems to me that oxygen plays a role in the process the same way that oxygen plays a role in the electron transport chain. In other words it's an important and necessary component, and metabolism of opiates will probably be inhibited if there is a lack of oxygen, but it's not like bumping their O2 sat from 96 to 100 is going to speed up the process.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/
Most opioids undergo extensive first-pass metabolism in the liver before entering the systemic circulation. First-pass metabolism reduces the bioavailability of the opioid. Opioids are typically lipophilic, which allows them to cross cell membranes to reach target tissues. Drug metabolism is ultimately intended to make a drug hydrophilic to facilitate its excretion in the urine. Opioid metabolism takes place primarily in the liver, which produces enzymes for this purpose. These enzymes promote 2 forms of metabolism: phase 1 metabolism (modification reactions) and phase 2 metabolism (conjugation reactions).

Phase 1 metabolism typically subjects the drug to oxidation or hydrolysis. It involves the cytochrome P450 (CYP) enzymes, which facilitate reactions that include N-, O-, and S-dealkylation; aromatic, aliphatic, or N-hydroxylation; N-oxidation; sulfoxidation; deamination; and dehalogenation. Phase 2 metabolism conjugates the drug to hydrophilic substances, such as glucuronic acid, sulfate, glycine, or glutathione. The most important phase 2 reaction is glucuronidation, catalyzed by the enzyme uridine diphosphate glucuronosyltransferase (UGT). Glucuronidation produces molecules that are highly hydrophilic and therefore easily excreted. Opioids undergo varying degrees of phase 1 and 2 metabolism. Phase 1 metabolism usually precedes phase 2 metabolism, but this is not always the case. Both phase 1 and 2 metabolites can be active or inactive. The process of metabolism ends when the molecules are sufficiently hydrophilic to be excreted from the body.
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"and that when an opiate OD (post naloxone) has recovered having a normal GCS and no signs of respiratory depression it is good practice to administer oxygen routinely regardless of oxygen saturations."

I haven't heard this. It's within the realm of possibility that this could be true - if oxygen is the limiting reactant in that stage of metabolism, then maybe... But if the person who told you this was not an MD or PhD, I would probably disregard that advice.
 
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I've never heard this and was unable to find any sources.
 
I've never heard of this, either.

I can't say for sure that it isn't theoretically possible that hyperoxia somehow speeds up the first or second phases of hepatic transformation, but I am very confident that oxygen has no clinically important effect in opioid metabolism.

Considering that the liver does little auto-regulation of its blood supply, I don't even see how the vasoactive effects of oxygen could play a role.
 
Lara said:
As a student I have been told that oxygen metabolizes opiates and reduces the half life of opiates which I found quite interesting and that when an opiate OD (post naloxone) has recovered having a normal GCS and no signs of respiratory depression it is good practice to administer oxygen routinely regardless of oxygen saturations. This is against our guidelines so I did a bit of research. However, doing my own literature search I cannot find any explanation for this. Has anyone else been told this? Can anyone direct me to any evidence to support this?
Click to expand...

This is a bit of an aside, but I just wanted to point something out.

We all know that the "elimination half life" of a drug refers to the length of time it takes for serum concentrations to be reduced by 50%, and that it takes roughly 5 half-lives for a drug to be completely eliminated from your system. But we also need to keep in mind when discussing drugs that the half-life of many drugs has little to do with the duration of their clinical effects. So saying "the half-life of a drug is X amount of time" really tells us nothing about how long we can expect the effects of the drug to last.

Propofol, for instance, has a half-life of 5 hours, but the clinical effects of a 1mg/kg dose last 10 minutes, tops, and within 30 minutes of receiving it, most people are 100% free of it's effects, even though their serum levels are not much lower than they were immediately after the drug was injected. Succinylcholine has a half life of seconds - 90% of sux that you give is metabolized before it even takes clinical effect. Some other drugs have clinical effects that last beyond the half-life of the drug, either because they are metabolized to pharmacologically-active metabolites that are actually more potent than the parent drug, or because they have such high affinity for their receptors that they remain bound even after serum concentrations fall.

Also, many of the drugs that we use in EM and anesthesia are highly protein-bound and/or lipid soluble, which means that the amount of drug injected and the amount available to be measured in the serum (which is what determines half-life) are very different.

I only mention this because many people use the term "half-life" as though it is an indication of the duration of a drug's clinical effects.
 
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I did a literature search, but I was unable to find any studies that supported the oxygen & opiates theory.
 
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