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Acetaminophen Mechanism of Action

Paracetamol (acetaminophen) is generally considered to be a weak inhibitor of the synthesis of prostaglandins (PGs). However, the in vivo effects of paracetamol are similar to those of the selective cyclooxygenase-2 (COX-2) inhibitors. Paracetamol also decreases PG concentrations in vivo, but, unlike the selective COX-2 inhibitors, paracetamol does not suppress the inflammation of rheumatoid arthritis.

It does, however, decrease swelling after oral surgery in humans and suppresses inflammation in rats and mice. Paracetamol is a weak inhibitor of PG synthesis of COX-1 and COX-2 in broken cell systems, but, by contrast, therapeutic concentrations of paracetamol inhibit PG synthesis in intact cells in vitro when the levels of the substrate arachidonic acid are low (less than about 5 mumol/L).

When the levels of arachidonic acid are low, PGs are synthesized largely by COX-2 in cells that contain both COX-1 and COX-2. Thus, the apparent selectivity of paracetamol may be due to inhibition of COX-2-dependent pathways that are proceeding at low rates.

This hypothesis is consistent with the similar pharmacological effects of paracetamol and the selective COX-2 inhibitors. COX-3, a splice variant of COX-1, has been suggested to be the site of action of paracetamol, but genomic and kinetic analysis indicates that this selective interaction is unlikely to be clinically relevant.

There is considerable evidence that the analgesic effect of paracetamol is central and is due to activation of descending serotonergic pathways, but its primary site of action may still be inhibition of PG synthesis.

The action of paracetamol at a molecular level is unclear but could be related to the production of reactive metabolites by the peroxidase function of COX-2, which could deplete glutathione, a cofactor of enzymes such as PGE synthase.

Medicines containing acetaminophen

Acetaminophen is the most common drug ingredient in America. More than 600 medicines contain acetaminophen. These include both prescription medicines and medicines available without a prescription, also called “over-the-counter,” or “OTC” medicines. To prevent acetaminophen overdose, you need to be able to read labels and recognize when their medicines contain acetaminophen. The active ingredients in OTC medicines are clearly listed on the label, and the word “acetaminophen,” is listed on the front of the package or bottle and in the Active Ingredient section of the Drug Facts label. On prescription labels, acetaminophen is sometimes listed as “APAP,” “acetam,” or other shorted versions of the word. To know what is in your medicines, read the list of active ingredients on the label each and every time you take a medicine.

You may be surprised to learn just how many medicines contain this acetaminophen:

Common Over-the-Counter Brand Name Medicines Containing Acetaminophen

  • Actifed®
  • Alka-Seltzer Plus LiquidGels®
  • Anacin®
  • Benadryl®
  • Cepacol®
  • Contac®
  • Coricidin®
  • Dayquil®
  • Dimetapp®
  • Dristan®
  • Excedrin®
  • Feverall®
  • Formula 44®
  • Goody’s®
  • Powders Liquiprin®
  • Midol®
  • Nyquil®
  • Panadol®
  • Robitussin®
  • Saint Joseph®
  • Aspirin-Free Singlet®
  • Sinutab®
  • Sudafed®
  • Theraflu®
  • Triaminic®
  • TYLENOL® Brand Products
  • Vanquish®
  • Vicks®
  • Zicam®
  • *And store brands

Common Prescription Medicines Containing Acetaminophen

  • Endocet®
  • Fioricet®
  • Hycotab
  • Hydrocet®
  • Hydrocodone Bitartrate
  • Lortab®
  • Percocet®
  • Phenaphen®
  • Sedapap®
  • Tapanol®
  • Tylenol® with Codeine
  • Tylox®
  • Ultracet®
  • Vicodin®
  • Zydone®
  • *And generic medicines

Important Acetaminophen Warning from FDA

Taking too much acetaminophen can cause liver damage, sometimes serious enough to require liver transplantation or cause death. You might accidentally take too much acetaminophen if you do not follow the directions on the prescription or package label carefully, or if you take more than one product that contains acetaminophen.

To be sure that you take acetaminophen safely, you should

  • not take more than one product that contains acetaminophen at a time. Read the labels of all the prescription and nonprescription medications you are taking to see if they contain acetaminophen. Be aware that abbreviations such as APAP, AC, Acetaminophen, Acetaminoph, Acetaminop, Acetamin, or Acetam. may be written on the label in place of the word acetaminophen. Ask your doctor or pharmacist if you don’t know if a medication that you are taking contains acetaminophen.
  • take acetaminophen exactly as directed on the prescription or package label. Do not take more acetaminophen or take it more often than directed, even if you still have fever or pain. Ask your doctor or pharmacist if you do not know how much medication to take or how often to take your medication. Call your doctor if you still have pain or fever after taking your medication as directed.
  • be aware that you should not take more than 4000 mg of acetaminophen per day. If you need to take more than one product that contains acetaminophen, it may be difficult for you to calculate the total amount of acetaminophen you are taking. Ask your doctor or pharmacist to help you.
  • tell your doctor if you have or have ever had liver disease.
  • not take acetaminophen if you drink three or more alcoholic drinks every day. Talk to your doctor about the safe use of alcohol while you are taking acetaminophen.
  • stop taking your medication and call your doctor right away if you think you have taken too much acetaminophen, even if you feel well.

Talk to your pharmacist or doctor if you have questions about the safe use of acetaminophen or acetaminophen-containing products.

Fioricet dosing information and fioricet overdose treatment

Usual Adult Dose of Fioricet for Headache:

Acetaminophen 300 mg, butalbital 50 mg, and caffeine 40 mg:
1 or 2 capsule(s) orally every 4 hours as needed. Maximum daily dose: 6 doses.

Acetaminophen 325 mg, butalbital 50 mg, and caffeine 40 mg:
1 or 2 tablet(s), capsule(s), or tablespoonful(s) orally every 4 hours.
Maximum daily dose: 6 doses

Acetaminophen 500 mg, butalbital 50 mg, and caffeine 40 mg:
1 tablet or capsule orally every 4 hours.
Maximum daily dose: 6 doses

Acetaminophen 750 mg, butalbital 50 mg, and caffeine 40 mg:
1 tablet orally every 4 hours.
Maximum daily dose: 5 tablets

Usual Pediatric Dose of Fioricet for Headache:

12 years and older:
Acetaminophen 300 mg, butalbital 50 mg, and caffeine 40 mg:
1 or 2 capsule(s) orally every 4 hours as needed. Maximum daily dose: 6 doses.

Fioricet Overdose Treatment

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include insomnia, restlessness, tremor, diarrhea, increased shallow breathing, uneven heartbeats, seizure (convulsions), or fainting.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Fioricet can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include insomnia, restlessness, tremor, diarrhea, increased shallow breathing, uneven heartbeats, seizure (convulsions), or fainting.

A single or multiple drug overdose with this combination product is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation.

Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.

To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.