werner@aecom.UUCP (Craig Werner) (01/20/86)
The mechanism of Aspirin is at the end of this article.
Aspirin has three actions tha make it ideal. It is an analgesic -
it releives pain. It is also an anti-inflammatory and anti-pyretic -- it
reduces swelling and fever, thus actually objectively lessens symptoms, in
addition to masking them by analgesia.
Tylenol (Acetominophen) is purely an analgesic without anti-inflam
or anti-pyretic effects. It has the advantage, however, of having less
short-term side effects, so is better tolerated. Moreover, it is the belief
of the author that a large portion of its success is due to the fact that
most people don't have about the objective relief of signs, as long as the
pain/discomfort goes away.
Phenacetin (Acetophenetidin) is an older drug, whose active metabolite
turns out to the Acetominophen. It was used very extensively at one point,
but it was found that heavy use or abuse causes permanent Kidney damage.
It is no longer available in the US.
The mechanism of Aspirin:
Aspirin mechanism is at least two fold. In its original form,as
Acetylsalicylic Acid, it can permanently acetylate the enzyme Cyclooxygenase
which is the first step towards Prostaglandin synthesis. This enzyme can
be reformed as soon as the Aspirin is degraded (about 15 minutes), except in
the platelets, where it is estimated 1 lick of 1 children's Aspirin will
destroy all Platelet cyclooxygenase for 2-3 days (as Platelets regenerate)
A second effect is caused by Salicylic Acid (sans Acetate) which blocks a
step towards Leukotriene formation, HPETE--> HETE, and the resulting
HPETE inhibits the Cyclooxygenase, and hence Prostaglandin formation.
Both Leukotrienes and Prostaglandins arise from an essential fatty
acid, Arachidonic Acid, so the pathways aren't as unlinked as it seems from
words. Moreover, both Leukotrienes and Prostaglandins are mediators of
inflammation, and both (but particularly PG-E2) have something to do with
fever.
Whether any of this has anything directly to do with Aspirin's
analgesic effect, I do not know. Obviously, Tylenol is proof tha one can
be analgesic without being anti-anything.
--
Craig Werner
!philabs!aecom!werner
"It's hard to argue with someone who knows what he's talking about."hachiya@uiucuxc.CSO.UIUC.EDU (01/23/86)
What's the word on ibruprophen (sp?), i.e. Nuprin, Advil?
dyer@harvard.UUCP (Steve Dyer) (01/25/86)
In article <2208@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: > Tylenol (Acetominophen) is purely an analgesic without anti-inflam > [-matory] > or anti-pyretic effects. It has the advantage, however, of having less > short-term side effects, so is better tolerated. Moreover, it is the belief > of the author that a large portion of its success is due to the fact that > most people don't have about the objective relief of signs, as long as the > pain/discomfort goes away. Um, acetaminophen is an effective antipyretic, and reduces fever about as well as aspirin. As Craig says, it is notoriously lacking a strong anti-inflammatory effect, unlike aspirin and ibuprofen. However, for most run-of-the-mill mild headaches and muscle aches, clinical anti- inflammatory actions are much less important than direct analgesia, which explains why acetaminophen is still fairly popular. This has been mentioned before, but it should be repeated that, although acetaminophen is better tolerated than aspirin in typical therapeutic doses, it is actually a lot more toxic than aspirin when taken in massive overdose. -- /Steve Dyer dyer@harvard.harvard.edu harvard!dyer
uribe@muddcs.UUCP (Lydia Uribe) (01/25/86)
In article <2208@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: > > Tylenol (Acetominophen) is purely an analgesic without anti-inflam >or anti-pyretic effects. It has the advantage, however, of having less >short-term side effects, so is better tolerated. Moreover, it is the belief >of the author that a large portion of its success is due to the fact that >most people don't have about the objective relief of signs, as long as the >pain/discomfort goes away. > Acetaminophen is indeed an effective antipyretic, of equal efficacy with aspirin. > >The mechanism of Aspirin: > Moreover, both Leukotrienes and Prostaglandins are mediators of >inflammation, and both (but particularly PG-E2) have something to do with >fever. > Prostaglandin-E is produced as a response to endogenous pyrogen and causes the hypothalamus to increase the body's temperature set point, resulting in fever. Aspirin and acetaminophen block this prostaglandin synthesis, causing the hypothalamus to re-establish the normal set point; they also cause increased heat dissipation (by cutaneous vasodilatation and increased sweating). > > Craig Werner (Reference: American Pharmaceutical Association, _Handbook of Nonprescription Drugs_, 7th edition, Chapter 11) Lydia Uribe ...scgvaxd!muddcs!uribe
werner@aecom.UUCP (Craig Werner) (01/30/86)
> > Moreover, both Leukotrienes and Prostaglandins are mediators of > >inflammation, and both (but particularly PG-E2) have something to do with > >fever. > > > Prostaglandin-E is produced as a response to endogenous pyrogen and causes > the hypothalamus to increase the body's temperature set point, resulting in > fever. Aspirin and acetaminophen block this prostaglandin synthesis, causing > the hypothalamus to re-establish the normal set point; they also cause > increased heat dissipation (by cutaneous vasodilatation and increased > sweating). > Lydia Uribe The above by L. Uribe is wrong in one respect. Yes, I did say Acetominophen was a pure analgesic without anti-imflammatory or anti-pyretic properties. Yes, it does in fact have anti-Pyretic properties (that was a misreading on my part) But, NO, Tylenol has no effect in inhibiting Prostaglandin synthesis. It is the only available analgesic that has this effect, which is why it is so easy on the stomach. Tylenol (Acetominophen) still lacks Anti-inflammatory properties. PG-E is only one of many endogenous pyrogens and does not directly cause fever if injected into the hypothalamus but is neccessary for the development of fever (put another way, it's necessary, but NOT sufficient). I do not know how Tylenol lowers fever, but it does not do it by blocking PG-E2 synthesis, as Aspirin does. Maybe it's a direct effect? -- Craig Werner !philabs!aecom!werner "The end. 94. 95. The very, very, very end."