Paracetamol and Alcohol

Subcutaneous

Paracetamol doesn't do much at all to cox 1 or 2, which is why we don't fully understand how it works and why it isn't classed as an NSAID- NSAIDS such as aspirin, ibuprofen, diclofenac work on inhibiting the release of prostaglandins which form the inflammatory response in our body- inhibiting this, involves working on the COX enzymes. It's not as comparable to aspirin or NSAIDS as your wiki article describes and is in a different class.

We don't know fully how paracetamol works (and tbh we kinda don't need too) but we do know it doesn't work as NSAIDS do

That is not how I understand it... i understand it (Paracetamol) as affecting pain relief via the brain (hypothalmus) which override an interluken increase in temp.The body then works to lower the temperature resulting in a reduction in fever like other anti-pyretics. Paracetamol along with NSAIDS inhibit prostagladin synthesis and show varying levels of anti inflammatory and anti-pyretic properties. it may not have as much anti-inflammatory properties/action as NSAIDs, but it does the exact same thing.

To say that you don't understand the pathways that it uses to produce its properties in not the same as saying that it does not produce a vasodilation effect. It means that the pathway is not fully understood, no one would argue that it does not produce the same vasodilation effect as NSAIDS, but to say that it has none is not true.

It may have less affinity for COX-1 than COX-2 but it does affect COX-1, as the link suggests:

http://www.fasebj.org/cgi/content/short/22/2/383

Reply 27

Revd. Mike

17

vnupe

Which I said in my response to the OP... it is right above your original response...

You didn't say that in your post. You stated (somewhat incorrectly) that paracetamol is a vasodilator, but that the dose wasn't sufficient to have an adverse effect. The implication in your post was that the adverse effects of mixing paracetamol and alcohol come from the supposed vasodilation - which is not true.

Reply 28

bestie

15

You'll be fine. The evidence that says it's dangerous to take alcohol and paracetamol together refers to overdose situations, and is generally only considered significant with alcoholics. This is because alcoholics generally have higher CYP P450 2E1 levels, which is responsible for the metabolism of paracetamol into it's toxic metabolite. Alcoholics also have lower levels of glutathione which is needed for glutathione conjugation which makes the toxic metabolite safe.

Reply 29

Gez1990

NHS advises that there will be no adverse effects as long as it was as much as the daily unit guideline allowance or under. For women that's 2-3 units so you'll be fine. Check the website if you want to look into this further.

Reply 30

Revd. Mike

You didn't say that in your post. You stated (somewhat incorrectly) that paracetamol is a vasodilator, but that the dose wasn't sufficient to have an adverse effect. The implication in your post was that the adverse effects of mixing paracetamol and alcohol come from the supposed vasodilation - which is not true.

Then you didn't understand what I wrote, I explained the effects of both drugs and then stated that the amounts she described should not have an adverse effect. I then added that there have been cases in which an adverse effect have been noted, but those are usually overdose cases.

That is what I wrote, and I do not understand why you are being so pedantic, but I stand behind what I wrote...

Reply 31

vnupe

That is not how I understand it... i understand it (Paracetamol) as affecting pain relief via the brain (hypothalmus) which override an interluken increase in temp.The body then works to lower the temperature resulting in a reduction in fever like other anti-pyretics. Paracetamol along with NSAIDS inhibit prostagladin synthesis and show varying levels of anti inflammatory and anti-pyretic properties. it may not have as much anti-inflammatory properties/action as NSAIDs, but it does the exact same thing.

To say that you don't understand the pathways that it uses to produce its properties in not the same as saying that it does not produce a vasodilation effect. It means that the pathway is not fully understood, no one would argue that it does not produce the same vasodilation effect as NSAIDS, but to say that it has none is not true.

It may have less affinity for COX-1 than COX-2 but it does affect COX-1, as the link suggests:

http://www.fasebj.org/cgi/content/short/22/2/383

well we had a lecture on its mechanism so it must be reasonably well understood... paracetomal mops up oxygen radicals which the cyclo-oxgenase enzyme requires to convert arachadonic acid to cyclic-endoperoxins and then to prostagladins - prostaglandins set the thermostatic level in the hypothalamus so by stopping the enzyme which creates them from working properly you alter PG production thus reduce pyrexia.. I don't think it acts by directly binding to COX but by removing radicals

Reply 32

Subcutaneous

Paracetamol doesn't do much at all to cox 1 or 2, which is why we don't fully understand how it works and why it isn't classed as an NSAID- NSAIDS such as aspirin, ibuprofen, diclofenac work on inhibiting the release of prostaglandins which form the inflammatory response in our body- inhibiting this, involves working on the COX enzymes. It's not as comparable to aspirin or NSAIDS as your wiki article describes and is in a different class.

We don't know fully how paracetamol works (and tbh we kinda don't need too) but we do know it doesn't work as NSAIDS do

paracetomol is actually often classed as an NSAID, it is in Rang & Dale infact though it has little appreciable affect on the inflammatory response (though in some cases it deos have an effect, eg following dental extraction), its mechanism is reasonably similar to other NSAIDS in that it acts on COX1 (and maybe 3) by mopping up oxygen radicals.. (at least that's what our pharm prof. says..)

Reply 33

Sambo2

well we had a lecture on its mechanism so it must be reasonably well understood... paracetomal mops up oxygen radicals which the cyclo-oxgenase enzyme requires to convert arachadonic acid to cyclic-endoperoxins and then to prostagladins - prostaglandins set the thermostatic level in the hypothalamus so by stopping the enzyme which creates them from working properly you alter PG production thus reduce pyrexia.. I don't think it acts by directly binding to COX but by removing radicals

Are you at undergrad or grad level and how do you explain it binding by over 85% (I think that is what the article stated, maybe higher) to COX-2, surely if it binds directly the O2 radicals and indirectly to COX 1 & or 2, then how do you account for such a high level of binding to COX-2?
Perhaps it has a greater affinity to COX-2 than one, which would explain its somewhat shaky reliability for vaso-dilation... hmmm ... I stand corrected...

Sorry I read it wrong, it does inhibit COX-2 much more than it inhibits COX-1 (as stated by the article), which is also the domain of many other NSAIDS. I definitely stand corrected on the way the mechanism works... thanks for clearing it up... Sambo1

As I stated though it does have some vaso-dialtion properties, not as extensive as other NSAIDS but nonetheless it has some.

Sorry if I am being pedantic... I am like a dog with a bone sometimes...

Where do you attend uni? Are you undergrad or grad?

Reply 34

bestie

15

vnupe

Are you at undergrad or grad level and how do you explain it binding by over 85% (I think that is what the article stated, maybe higher) to COX-2, surely if it binds directly the O2 radicals and indirectly to COX 1 & or 2, then how do you account for such a high level of binding to COX-2?
Perhaps it has a greater affinity to COX-2 than one, which would explain its somewhat shaky reliability for vaso-dilation... hmmm ... I stand corrected...

Sorry I read it wrong, it does inhibit COX-2 much more than it inhibits COX-1 (as stated by the article), which is also the domain of many other NSAIDS. I definitely stand corrected on the way the mechanism works... thanks for clearing it up... Sambo1

As I stated though it does have some vaso-dialtion properties, not as extensive as other NSAIDS but nonetheless it has some.

Sorry if I am being pedantic... I am like a dog with a bone sometimes...

Where do you attend uni? Are you undergrad or grad?

It's effects on COX 1 and 2 have nothing to do with it's toxicity.

Reply 35

Subcutaneous

Sambo2

well we had a lecture on its mechanism so it must be reasonably well understood... paracetomal mops up oxygen radicals which the cyclo-oxgenase enzyme requires to convert arachadonic acid to cyclic-endoperoxins and then to prostagladins - prostaglandins set the thermostatic level in the hypothalamus so by stopping the enzyme which creates them from working properly you alter PG production thus reduce pyrexia.. I don't think it acts by directly binding to COX but by removing radicals

When working with specialist nurses, I was told there was a lot of theories into how paracetamol works, and small studies, but there has never been enough to really give us a proper definition, purely because we don't really need to know how it works, its too expensive and its a very good drug for the economy. If like you said about that the mechanism was truly similar to an NSAID, we'd have to deal with the same precautions..however this isn't the case. Fact is there isn't much research, there is a lot of speculation and ideas- but its simply not needed. I'd really like to see vnupes ideas about vasodilation then, as if this is the case then dear god... :rofl:

Reply 36

bestie

It's effects on COX 1 and 2 have nothing to do with it's toxicity.

Nobody was postulating its interaction with COX-1 or 2 had anything to do with this toxicity? Where did you get that from?

Reply 37

vnupe

Are you at undergrad or grad level and how do you explain it binding by over 85% (I think that is what the article stated, maybe higher) to COX-2, surely if it binds directly the O2 radicals and indirectly to COX 1 & or 2, then how do you account for such a high level of binding to COX-2?
Perhaps it has a greater affinity to COX-2 than one, which would explain its somewhat shaky reliability for vaso-dilation... hmmm ... I stand corrected...

Sorry I read it wrong, it does inhibit COX-2 much more than it inhibits COX-1 (as stated by the article), which is also the domain of many other NSAIDS. I definitely stand corrected on the way the mechanism works... thanks for clearing it up... Sambo1

As I stated though it does have some vaso-dialtion properties, not as extensive as other NSAIDS but nonetheless it has some.

Sorry if I am being pedantic... I am like a dog with a bone sometimes...

Where do you attend uni? Are you undergrad or grad?

Bute med school, undergrad - I'm no expert, this is what I was taught though..

Reply 38