Discussions that mention tylenol

Pain Management board


Hiya Shoreline, how are you doing? I have been away for a little over a week, was wondering how youre doing? Last I spoke with you, you had a nasty fall coming out of the shower, and was wondering if youre doing better now? I hope so! I even mentioned you in my prayers---I figured any little bit helps, hehehe. I was reading thru some of the posts Ive missed, and see youve been back in your usual top-notch helpful form, so Im assuming you are doing better---something everyone on this board is happy about, Im sure, hehe.

On a side note, I had a curious question about something you said in one of your always-informative posts. Its nothing major, more just something I found fascinating, more than anything. You were talking about an enzyme, and its something Ive never heard of, so Ill paste it here to show you part of what I read:

"If you have several meds using the same route of eliminaton, serum levels can rise to unsafe levels, the Cytochrome P450 Inhibitors like tagament can either reduce or increase the serum level of several drugs including opiates making them dangerous, alcohol and opiate or alcohol and benzo's are dangerous. But if your not overloading the ability of the P450 cytochrome enzyme it can effectvely break down and excreete any amount of opiate unless you using other drugs that take the same route of elimination using the same enzyme. Cold meds, stomache meds and nausea meds can cause problems due to this same enzyme.OxyC uses the P450, Morphine uses the P450, and many otrher drugs use the same cytochrome and if you overload this one enzymes abilty to break down meds down you will have consequences and sometimes lethal consequences. But pure opiates alone, as much as I have researched don't damage the liver. - Shoreline."

I found this fascinating, because I had never even heard of such a problem. I was wondering, can things like the Ibuprofen and Tylenol add to this problem? Im wondering now if part of the problems I was having before might have been caused by some of the medications I was taking at the same time. Is it a certain amount of time before the enzyme gets "refreshed" or something, or taking certain meds hours apart might help? Just wondering exactly how to be cautious about the "same route meds", for those of us who take several different types of medication, since it both surprised and interested me at the same time.

Anyways, thats more of a curious question, so if youre still not quite back up to your old-self after what youve been thru---by all means take your time! I wanted to check on ya more than anything, so if youre time to reply is limited just lemme know how you are holding up! Or if youre glued to the election coverage like alot of us here probably are, I will talk to ya tomorrow, hehe. Take Care Dave!
Hey Phlox, There is usually a warning on the paper work you get about interaction with other meds that use the same liver enzymes to break them down.

West Virginia University School of Pharmacy, Morgantown, West Virginia

Many drug interactions are a result of inhibition or induction of cytochrome P450 enzymes (CYP450). The CYP3A subfamily is involved in many clinically significant drug interactions, including those involving nonsedating antihistamines and cisapride, that may result in cardiac dysrhythmias. CYP3A4 and CYP1A2 enzymes are involved in drug interactions involving theophylline. CYP2D6 is responsible for the metabolism of many psychotherapeutic agents. The protease inhibitors, which are used to treat patients infected with the human immunodeficiency virus, are metabolized by the CYP450 enzymes and consequently interact with a multitude of other medications. By understanding the unique functions and characteristics of these enzymes, physicians may better anticipate and manage drug interactions and may predict or explain an individual's response to a particular therapeutic regimen.

The basic purpose of drug metabolism in the body is to make drugs more water soluble and thus more readily excreted in the urine or bile.1,2 One common way of metabolizing drugs involves the alteration of functional groups on the parent molecule (e.g., oxidation) via the cytochrome P450 enzymes. These enzymes are most predominant in the liver but can also be found in the intestines, lungs and other organs.3-6 These cytochrome P450 enzymes are designated by the letters "CYP" followed by an Arabic numeral, a letter and another Arabic numeral (e.g., CYP2D6).7 Each enzyme is termed an isoform since each derives from a different gene. It should be noted, however, that structural similarity of enzymes cannot be used to predict which isoforms will be responsible for a drug's metabolism.

Drug interactions involving the cytochrome P450 isoforms generally result from one of two processes, enzyme inhibition or enzyme induction. Enzyme inhibition usually involves competition with another drug for the enzyme binding site. This process usually begins with the first dose of the inhibitor,8,9 and onset and offset of inhibition correlate with the half-lives of the drugs involved.9


Until genetic tests for isoform expression become available, a physician can often anticipate drug interactions in a patient by knowing which medications inhibit or induce P450 enzymes.SSRIs and cimetidine inhibit metabolism of tricyclic antidepressants, but the clinical significance of this finding depends on individual genetic variations and concomitant medications.


Enzyme induction occurs when a drug stimulates the synthesis of more enzyme protein,9 enhancing the enzyme's metabolizing capacity. It is somewhat difficult to predict the time course of enzyme induction because several factors, including drug half-lives and enzyme turnover, determine the time course of induction.

If you do a google search for cytochrome p450 you will get tons of info. It's alslso not just drugs that use this enzyme but foods too. Grapefruit juice is a notorious cyp 450 inhibtor.
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I can do a quick search adding Tylenol to the search like Tylenol and the cytochrome p450.
Be right back.

Bye the way, I am feeling better now, It took agood 5 days for things to setle down and I've just been buisy wit my daughter and haloween and yesterday I got to test my standing limits again while waiting to vote. I did manage 90 minutes of alternating from standing, kneeling and sitting on the curb, But was a sweaty mess by the time I got my name checked. I gueess it's good to test your limits from time to time. :eek:
Take care, Dave
PS IF I find anything about Apap and p450 I will let you know
Hey phlox , just quickly it loks like you would have to take overdose amounts to create a problem with this enzyme. I did a search using tha phrase
cytochrome p450 Tylenol interactions and did get several more articles about P450 and one particulalry about Tylenol and the history or apap , way more than anyone nees to know unless apearing on Jeopardy. LOL

Metabolism

Acetaminophen is metabolized primarily in the liver, where most of it is converted to inactive compounds by conjugation with sulfate and glucuronide, and then excreted by the kidneys. Only a small portion is metabolized via the hepatic cytochrome P450 enzyme system. The toxic effects of acetaminophen are due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine), not acetaminophen itself or any of the major metabolites. This toxic metabolite reacts with sulfhydryl groups. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.

Toxicity
Overview


Acetaminophen is one of the safest medications available for analgesia. The drug lacks effects on the cyclooxygenase system so does not cause injury to the esophagus, stomach, small intestine or large intestine, in contrast to NSAID's. Additionally, patients with kidney disease are able to take acetaminophen wheras NSAID's can cause acute renal failure in certain patients. Acetaminophen also lacks problems with drug interactions. The analgesic potency is equivalent in non-inflammatory conditions to NSAIDs as long as the dose of acetaminophen is adequate. 1 gram of acetaminophen three times a day is equivalent to analgesia provided by NSAID's in osteoarthritis, for example. When coadministered with amitriptyline 50 mg twice a day, the combination is as effective as acetaminophen with codiene, but does not lose effectivness as an analgesic over time as does chronic administration of narcotics. For children, acetaminophen does not contribute to the risk of Reye's syndrome in patients with viral illnesses. These factors have made acetaminophen the anagesic of choice for mild and moderate pain for patients in hospitals and makes it the leading analgesic for outpatient use.

However, acetaminophen single doses above 10 grams or chronic doses over 5 grams per day in a well nourished non-consumer of alcohol, or above 4 grams per day in a poorly nourished consumer of alcohol, can cause significant injury to the liver. Without timely treatment, acetaminophen overdoses can lead to liver failure and death within days. Because of the wide over-the-counter availability of the drug, it is often used in suicide attempts.

Acetaminophen should not be taken after alcohol consumption, because the liver, when engaged in alcohol breakdown, cannot properly dispose of acetaminophen, thus increasing the risk of hepatotoxicity.



Mechanism of action
As mentioned above, acetaminophen is mostly converted to inactive compounds by conjugation with sulfate and glucuronide, with a small portion being metabolized via the cytochrome P450 enzyme system. The cytochrome P450 system oxidizes acetaminophen to produce a highly reactive intermediary metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione.

In cases of acetaminophen toxicity, the sulfate and glucuronide pathways become saturated, and more acetaminophen is shunted to the cytochrome P450 system to produce NAPQI. Subsequently, hepatocellular supplies of glutathione become exhausted and NAPQI is free to react with cellular membrane molecules, resulting in widespread hepatocyte damage and death, clinically leading to acute hepatic necrosis. In animal studies, 70% of hepatic glutathione must be depleted before hepatotoxicity occurs.


If you have specific meds your worried about I can check, But generally Antidepressants, cold medications, and some of the benzo's and many other drugs that aren't involved in pain mnagement are metabolized by P450
http://medicine.iupui.edu/flockhart/table.htm
Hey Phlox, The last article suggested injesting 5 or 6 pounds of this material before causing chronic renal faulure, But when I think of when My pain went unmanaged for years I would go through 500 count botles of Tylenol and Ibuprofin in 2-3 months. 1000mgs of apap and 600mgs of IBU was my standard cocktail every 4 hours for several years.

17,000 people die every year from OTC medications

Put 15 500 count bottles on the scale and I'll bet you have 5 pounds of crud your kidneys had to excreete. I'm sure I have consumed that much, If I go low and figure 3 bottles of each for 5 years thats 30 500 count bottles of that crud. Then add in the hydro/apap and oxy/apap from 93-2000 I know I put that much in me. Fortuantely I haven't had an alcoholic drink since I was 23 years old. I Drank like a fish in New orleans and made myself sick and never developed a taste for it again. I remeber trying to swig Vodka to kill the pain and simply not being able to do it. I doubt I could do 5 shots even if I was on fear factor competing for 50K. I'de rather eat a roach than drink.LOL
Take care, Dave