I saw some post here and other threads about COX inhibitors and Tylenol (a.k.a. acetaminophen or paracetamol) and wanted to try to advance the conversation a little. This post is only for POISers who are taking prepacks or pharmaceutical drugs
Nothing that I say here can substitute for treatment by a personal physician. Excedrin (acetaminophen, aspirin, caffeine) is a drug combination that is FDA approved (in the USA) to treat migraines and is an over-the-counter (OTC) drug. These three drugs taken together are synergetic and more effective together than if they are taken individually. Some POISers try the drugs one-at-a-time (like trying only acetaminophen) to see if it works before stacking the other drugs.
Trying the drugs one-at-a-time will not be effective at stopping POIS. From my experience and from what other POISers have said, trying the drugs individually will result in you taking more doses over longer periods of time. More doses lead to more side-effects. Taking the 3-drug combination (Excedrin) can help prevent POIS with one dose (this means less drugs and fewer side-effects).
Excedrin:- caffeine: PDE(1,4,5) inhibitor, adenylyl cyclase inhibitor, NF-kB downregulator, vasocontrictor (through adenosine receptor)
- aspirin: antioxidant, COX inhibitor, vasoconstrictor (through PGE2 downregulation)
- acetaminophen: cannabinoid reuptake inhibitor, NF-kB downregulator
My first trial of Excedrin is discussed
here. In my tests of Excedrin, I found that the drug is most effective when timed before the orgasm. I made the concept figure below to explain why I believe timing is very important:
Acetaminophen, aspirin, caffeine have similar
timing pharmacokinetics. After you start (t
start) the Excedrin dose, the blood concentration peaks (t
max) at about 90 min. Then there is roughly a 2 hour window (t
1/2) when it is safe to orgasm. The reason for waiting until after t
max is that absorption of the drug from the blood stream into the cells usually lags behind in time by about 30min. Below are more accurate plasma time-points graphs for Tylenol (Acetaminophen). Note that it takes longer for Acetaminophen to cross the blood-brain-barrier (BBB)(see Mean Cerebrospinal Fluid Values| right graph):
Figure from:
The Role of Intravenous Acetaminophen in Multimodal Pain Protocols for Perioperative Orthopedic Patients (P. LACHIEWICZ, 2013) When you time the drug(s) properly, they are more effective at stopping the arachidonic acid cascade. And when the drug is more effective, you can take less of the drug and experience fewer side-effects. If you do not time the drugs properly, they will be less effective and you will have to take more of the drugs to experience relief (more-drugs = more-side-effects). So the timing is a safety issue just as much as it is a POIS-relief issue. There are several differences between migraines and POIS. So I did a few (about nine) modified-Excedrin trials which resulted in the
Beta-herpes virus stack. This stack is customized more for POIS rather than for migraines. In the Beta-herpes virus stack, I basically replaced aspirin with indomethacin and added vitamin D3. Selenium and N-acetylcysteine were added as detox antioxidants to boost glutathione (
Ref). For me,
this stack was 100% effective with a single dose, and it was more effective at preventing POIS than Excedrin.
Indomethacin (oral, 50mg) (t
max = 2 hours, t
1/2 = 4 hours):
Figure from:
TIVORBEX (indomethacin): The first low-dose SoluMatrix indomethacin. (blood-plasma time points)
More indomethacin trials/experiences from other POISers can be found
here. In theory, the COX inhibitor Diclofenac is the best COX inhibitor for POIS. It is a better COX-2 inhibitor than indomethacin (see
post) and has better BBB penetration. However, I have never tried Diclofenac. So I do not know whether it works in practice.
Diclofenac (oral, 50mg) (t
max = 90min, t
1/2 = 80 min):
Figure from:
DYLOJECT ACHIEVES CMAX 5 TO 7 TIMES ORAL IMMEDIATE-RELEASE (IR) DICLOFENAC Celebrex is not a good prepack drug since it has to be taken long-term. With that said, no COX-inhibitor can prevent POIS on its own. With that said, from my trials of the Excedrin and alternative COX-inhibitors, it seemed that
I needed a COX-inhibitor and a NF-kB inhibitor to prevent POIS. Taking only COX inhibitors or taking only NF-kB inhibitors did not work no matter how high the dose was. But I must reiterate,
for any drug you try, the only way to know if it works or not is to have the right timing and therapudic dose information.Please consult your doctor to make sure that these drugs are safe for you. Also make sure that any other medications you may be taking do not interact negatively with COX inhibitors, cannabinoids or caffeine before trying the Beta-herpes Virus Stack.Some additional plasma time-point graphs are shown below for other popular supplements:
N-Acetylcysteine (t
max = 2 hours, t
1/2 = 18 hours):
Figure from:
Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study (SC Green, et. al., 2016)Tri-methyl-glycine (betain, TMG) (t
max = 55 min, t
1/2 = 14 hours):
Figure from:
Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria (BC Schwahn, et. al., 2003)Taurine (t
max = 2 hours, t
1/2 = 1 hour):
Pharmacokinetics of Oral Taurine in Healthy Volunteers (M Ghandforoush-Sattari, et. al., 2010)Vitamin C (ascorbate, oral 1.25g) (t
max = 2 hours, t
1/2 = 7 hour):
Vitamin C pharmacokinetics:
Fig. from: "Vitamin C pharmacokinetics: implications for oral and intravenous use", Ann Intern Med. 2004 (
Ref) (click figure to show full resolution)
Nicotinic acid (flush niacin) (t
max = 4 hours, t
1/2 = 2 hours):
Figure from:
Niacin and fibrates in atherogenic dyslipidemia: Pharmacotherapy to reduce cardiovascular risk (MJ Chapman, 2010)*Update: I added the timing (90min) and dosage (50mg) information for Diclofenac to satisfy a concern that Muon had.
