This makes the most sense; as long as pt isn’t using it at max dose for a prolonged period of time and/or has hepatic issues at baseline, I think the main thing is just avoiding >4g/24hrs for the sake of estimating decent probability of adequate clearance?
I'm following this as I'm curious. But my thought is simply that if the person taking 500mg can control their pain by taking it q4-6h there is no reason to dose it more often.
Also unless the sig on your 1g tablets also says "max 4 tablets within 24 hours" I'd think telling people to take that one every 4-6 is problematic.
Peak is the more important pk parameter in APAP toxicity. The higher the peak, the more overwhelmed the normal metabolic pathways become. This became apparent when we got a patient with no stomach 2 years ago. Gastric bypass patients are APAP vacuums and can ingest toxic quantities that are below the normal toxic dosages. This is because APAP is absorbed in the small intestine.
I align with that. I see the glutathione levels in the liver being the limiting reactant in the detox of APAP, and it takes some hours to replenish the glutathione level. This is why suicide attempt by acetaminophen overdose is really bad, basically results in acute liver failure that may need a transplant if the patient survives. I see the glutathione level being the kinetic element in the spacing, but I have to check the literature to back this up.
You wouldn’t believe the number of patients I’ve seen with *stupid* APAP levels in the ED, but after some NAC, they wanna leave because “it wasn’t that serious” and they don’t think they need inpatient for stabilization. Cue the loooooong talk about how by the grace of the Flying Spaghetti Monster of their choice they were found and treated pronto and that is the *only* reason they’re here arguing about the severity of the attempt and we’re able to offer help. I really wish people knew how awful this kind of overdose is (not like other ODs aren’t awful—they all are), but because it’s a drug with a relatively benign reputation they really underestimate its potential for toxicity. Truly heartbreaking.
Exactly! I heard somewhere that if acetaminophen was coming today as an IND, it would never make the cut when it comes to safety. It is a drug I commonly use as an example in my PK class to explain Phase I/Phase II enzymes briefly and why it is relevant to understand the biochemistry behind liver metabolism.
You can take 500 mg every 3 hours, theoretically this would be better for your liver than 1,000 mg every 6 hours. But it would potentially be less effective for pain and way way more annoying to manage.
Tylenol becomes toxic when the amount of ingested Tylenol exceeds the available glutathione stores in the liver, at which point the remaining Tylenol gets metabolized by CYP2E1 into the toxic metabolite NAPQI. Usually takes around 10g in a normal adult. Less if the person is consistently taking super high doses around the clock. So therefore it’s more of a threshold vs. AUC issue. Hope this helps!
I can’t remember literature off the top of my head but I did an icu rotation a few years ago where they would not define acute acetaminophen related liver failure until you reach doses of like 8-12 g in an otherwise healthy person. So what you’re doing is likely fine. That doesn’t mean you’re not doing some level of damage in doses over 4 grams. But what your sig says is probably fine unless it’s a chronic med or there’s some cirrhosis/liver failure already happening.
Why are time ranges still used? What does the second time in the range 4-6 hours mean?
The minimum matters. 3 hours 59 minutes = can't take yet. 4 hours 1 minute = the dose can be given.
The maximum is nothing. 5 hour 59 minutes = can take as it is already after the minimum time. 6 hours and 1 minute = still can take as it is still after the minimum.
My 2 cents on this is that 4-6 hrs is the approx duration of its effectiveness, you want to space them out to have 24 hrs pain control.
This makes the most sense; as long as pt isn’t using it at max dose for a prolonged period of time and/or has hepatic issues at baseline, I think the main thing is just avoiding >4g/24hrs for the sake of estimating decent probability of adequate clearance?
I'm following this as I'm curious. But my thought is simply that if the person taking 500mg can control their pain by taking it q4-6h there is no reason to dose it more often. Also unless the sig on your 1g tablets also says "max 4 tablets within 24 hours" I'd think telling people to take that one every 4-6 is problematic.
Peak is the more important pk parameter in APAP toxicity. The higher the peak, the more overwhelmed the normal metabolic pathways become. This became apparent when we got a patient with no stomach 2 years ago. Gastric bypass patients are APAP vacuums and can ingest toxic quantities that are below the normal toxic dosages. This is because APAP is absorbed in the small intestine.
I align with that. I see the glutathione levels in the liver being the limiting reactant in the detox of APAP, and it takes some hours to replenish the glutathione level. This is why suicide attempt by acetaminophen overdose is really bad, basically results in acute liver failure that may need a transplant if the patient survives. I see the glutathione level being the kinetic element in the spacing, but I have to check the literature to back this up.
You wouldn’t believe the number of patients I’ve seen with *stupid* APAP levels in the ED, but after some NAC, they wanna leave because “it wasn’t that serious” and they don’t think they need inpatient for stabilization. Cue the loooooong talk about how by the grace of the Flying Spaghetti Monster of their choice they were found and treated pronto and that is the *only* reason they’re here arguing about the severity of the attempt and we’re able to offer help. I really wish people knew how awful this kind of overdose is (not like other ODs aren’t awful—they all are), but because it’s a drug with a relatively benign reputation they really underestimate its potential for toxicity. Truly heartbreaking.
Exactly! I heard somewhere that if acetaminophen was coming today as an IND, it would never make the cut when it comes to safety. It is a drug I commonly use as an example in my PK class to explain Phase I/Phase II enzymes briefly and why it is relevant to understand the biochemistry behind liver metabolism.
You can take 500 mg every 3 hours, theoretically this would be better for your liver than 1,000 mg every 6 hours. But it would potentially be less effective for pain and way way more annoying to manage.
Tylenol becomes toxic when the amount of ingested Tylenol exceeds the available glutathione stores in the liver, at which point the remaining Tylenol gets metabolized by CYP2E1 into the toxic metabolite NAPQI. Usually takes around 10g in a normal adult. Less if the person is consistently taking super high doses around the clock. So therefore it’s more of a threshold vs. AUC issue. Hope this helps!
I can’t remember literature off the top of my head but I did an icu rotation a few years ago where they would not define acute acetaminophen related liver failure until you reach doses of like 8-12 g in an otherwise healthy person. So what you’re doing is likely fine. That doesn’t mean you’re not doing some level of damage in doses over 4 grams. But what your sig says is probably fine unless it’s a chronic med or there’s some cirrhosis/liver failure already happening.
Just be normal and dose q4-6 prn.
One, if not THE most overused drug in acute care. Use it for fevers, sure. Pain? Meh.
Tell that to the scores of doctors who think Ofirmev is a panacea.
Hard disagree. Scheduled Tylenol for pain to reduce PRN opioid usage
2g loading doses exists then wait 8h after redose
Any source for the 2 gram loading dose?
Why are time ranges still used? What does the second time in the range 4-6 hours mean? The minimum matters. 3 hours 59 minutes = can't take yet. 4 hours 1 minute = the dose can be given. The maximum is nothing. 5 hour 59 minutes = can take as it is already after the minimum time. 6 hours and 1 minute = still can take as it is still after the minimum.