Acetaminophen Mechanism of Action

Acetaminophen is a pain reliever and fever reducer. Butalbital is in a group of drugs called barbiturates. It relaxes muscle contractions involved in a tension headache. Caffeine is a central nervous system stimulant. It relaxes muscle contractions in blood vessels to improve blood flow.

Acetaminophen, butalbital, and caffeine is a combination medicine used to treat tension headaches that are caused by muscle contractions.

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.

Currently, products that contain butalbital/aspirin/caffeine are classified as schedule III controlled substances; butalbital products listed on the DEA’s list of Exempted Prescription Products, including butalbital/acetaminophen/caffeine products, are unscheduled. This rule change eliminates the disparity of scheduling for butalbital-containing products and recognizes all products containing butalbital, including Fioricet, as schedule III controlled substances under the Iowa uniform Controlled Substances Act.

Important Acetaminophen Warning from FDA

Fioricet capsules contain a combination of acetaminophen, butalbital, and caffeine. Acetaminophen is a pain reliever and fever reducer. Butalbital is in a group of drugs called barbiturates. It relaxes muscle contractions involved in a tension headache. Caffeine is a central nervous system stimulant. It relaxes muscle contractions in blood vessels to improve blood flow.

Acetaminophen APAP Caffeine
Acetaminophen APAP Caffeine

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.

Are there alternatives to butalbital-acetaminophen-caffeine?

If you’re not able to take BAC, a healthcare professional may suggest one or more of the following interventions:

  • lifestyle changes, including staying hydrated, getting adequate sleep, and reducing stress
  • over-the-counter medications such as aspirin, acetaminophen, or ibuprofen, with or without caffeine
  • other prescription medications, depending on the underlying cause of your headache, such as:
    • ketorolac
    • naproxen
    • antidepressants
    • beta-blockers

What is the Max Dosage of Acetaminophen ?

Acetaminophen, which is also known as paracetamol, is a commonly used OTC (over-the-counter) pain reliever (analgesic) and fever reducer (antipyretic). People use it for headaches, and minor aches and pain. Liver injury from acetaminophen overdose remains a serious public health problem despite ongoing regulatory and educational efforts over the past several years to improve the safe use of medicines that contain acetaminophen.

Fioricet contains acetaminophen 325 mg per tablet. The max dosage of an adult for acetaminophen goes down from 4000mg to 3000mg per day (http://www.medicalnewstoday.com/articles/231915.php). So only acetaminophen, you should not take more than eight tablet fioricet per day. IF you take more than eight fioricet tablet per day, you will hurt your liver.

acetaminophen

From tylenol website, they lowered the maximum daily dose for single-ingredient Extra Strength TYLENOL® (acetaminophen) products sold in the U.S. from 8 pills per day (4,000 mg) to 6 pills per day (3,000 mg). The dosing interval has also changed from 2 pills every 4 – 6 hours to 2 pills every 6 hours.

Recommended dosages for this drug are based on someone’s age and weight and also the scheduled frequency of taking it.

Acetaminophen overdoses happen when someone:

  • Takes too much of the pain medication at one time
  • Re-doses too soon
  • Takes multiple medications at the same time that also contain acetaminophen

For a healthy adult weighing at least 150 pounds, the maximum daily dose of acetaminophen is 4,000 milligrams (mg). However, you can experience liver damage even if you stay at or below 4,000mg if you take this maximum dose for an extended period.

As such, doctors often recommend a maximum daily dose closer to 3,000 mg. Read the drug label carefully and know exactly how much acetaminophen is in each tablet, capsule or liquid dose.

The following table further details acetaminophen dosage recommendations:

325mg 500mg 650mg (extended-release)
Take how many pills at a time? 1 or 2 1 or 2 1 or 2
Take how often? Every 4 to 6 hours Every 4 to 6 hours Every 8 hours
Safest maximum daily dose for most adults 8 pills 6 pills 4 pills
Never take more than this in a 24-hour period 12 pills (3,900mg) 8 pills (4000mg) 6 pills (3,900mg)

For children, acetaminophen doses usually come in 80mg and 160mg, although many of the medications are delivered in liquids (syrups), not pills or chewable tablets.

Body weight plays more of a factor in dosing for kids than it does for adults. The smaller and younger a child is the more careful adults must be when giving the correct dosage. Get an updated weight on your child before administering acetaminophen or any medications that have acetaminophen in them.

Here are basic guidelines for children taking acetaminophen:

Child’s Weight Syrup/Liquid (160mg) Pills (80mg)
24 to 35 lbs 1 tsp 2 tablets
26 to 47 lbs 1.5 tsp 3 tablets
48 to 59 lbs 2 tsp 4 tablets
60 to 71 lbs 2.5 tsp 5 tablets
72 to 95 lbs 3 tsp 6 tablets
96 or more lbs 4 tsp 8 tablets

An important note: Children under the age of 6 should not take more than one medication at a time that has acetaminophen as an active ingredient.

If your child is younger than 2 years old, check with your pediatrician, an urgent-care physician or pharmacist before giving any medication that contains acetaminophen.

For adults and children, if the recommended dosages don’t relieve symptoms, consult with a doctor before making the decision to increase any dosages. Acetaminophen toxicity can lead to life-threatening acute liver failure.

How Often Can You Take Acetaminophen?

Dosing frequency is a crucial part of how much acetaminophen you can take at one time or during a one-day period. How long it takes acetaminophen to work, duration of its effects, and how long the medication stays in your body determine how often you should re-dose.

The recommended frequency is every four to six hours. After ingestion, it takes acetaminophen between 30 and 90 minutes to start working. Several factors, including formulation, other drug and alcohol intake influence the effects of acetaminophen.

If you have questions about acetaminophen and the right dose for you, speak with your doctor. Discuss other medications you may be taking and your overall health to determine the best plan for your needs.

How Long Does Acetaminophen Work For?

Acetaminophen typically lasts four hours for both pain relief and fever reduction. This is why the recommended dosing frequency is no more than every four to six hours.

The biological half-life of a drug plays an essential role in its effectiveness and safety. It is also an important factor for determining dosage recommendations.

How Long Does Acetaminophen Stay in Your System?

Scientists gauge the time it takes for your body to eliminate acetaminophen from the system by using the medication’s estimated half-life. A drug’s half-life is the time it takes for half a dose to be metabolized and eliminated from your bloodstream. Acetaminophen half-life elimination for therapeutic doses is between one and two-and-a-half (2.5) hours.

However, the expected half-life of acetaminophen can vary from person to person. Factors that affect its half-life include age, genetics, weight and overall health. Generally, a therapeutic dose of acetaminophen flushes fully from your system within 24 hours.

An acetaminophen overdose can extend the half-life of the drug to four and eight, meaning it may take up to three times longer for you to get the drug out of your body. If you re-dose too soon following even a small overdose period, it can lead to an acute case of severe acetaminophen toxicity.

How Much Acetaminophen Is Too Much?

Aside from determining how long acetaminophen works and how long it stays in your system, the drug’s half-life also determines how much is too much to take. The goal of medication is to achieve a steady state, at which point the amount of the drug you ingest and the amount that’s eliminated are equal.

Regardless of a drug’s half-life, it takes approximately four times longer for its concentration to reach a steady state in your body. Acetaminophen side effects often occur when you’re not in a steady state. A small amount of acetaminophen is metabolized into the compound NAPQI, which can cause liver toxicity in large amounts.

Taking too much acetaminophen can cause acute liver damage, which can be fatal. As such, you should not exceed the 4,000 mg maximum daily dose recommendation (you should ideally stay closer to 3,000 mg). Acetaminophen may also effect blood pressure. One 2022 clinical research study found that regular daily intake of 4 g acetaminophen increased systolic blood pressure in individuals with hypertension by about 5 mm Hg compared with a placebo.

Primary symptoms of acetaminophen overdose are:

  • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
  • Excessive sweating
  • Jaundice
  • Irritability
  • Seizures
  • Coma

In case you suspect someone took an overdose of acetaminophen or if you see someone exhibit the above symptoms, you should immediately call 911, emergency medical services, a poison control center or a doctor.

Emergency room treatment will depend on the presenting condition and other drugs that may have been taken. If you make it to the hospital just after taking an overdose, the doctor will attempt to empty your stomach.

Doctors like to prescribe a dose of activated charcoal within four hours of an overdose to bind drugs remaining in your gastro-intestinal tract. They also give N-Acetylcysteine, an antidote for acetaminophen toxicity, orally or intravenously within eight hours.

Emergency doctors recommend that anyone suspected to have taken an acetaminophen overdose get treatment as soon as possible, even before the symptoms occur. Early treatment of acetaminophen overdose can improve the outcome significantly.

 

Medicines Containing Acetaminophen

Acetaminophen is the most common drug ingredient in America. Fioricet capsules contain a combination of acetaminophen, butalbital, and caffeine. Acetaminophen is a pain reliever and fever reducer. Butalbital is in a group of drugs called barbiturates. It relaxes muscle contractions involved in a tension headache. Caffeine is a central nervous system stimulant. It relaxes muscle contractions in blood vessels to improve blood flow.

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