What Is Acetaminophen?
Acetaminophen is a common drug prescribed for pain and fever. It is both an analgesic (pain relievers) and antipyretic (used to treat fevers).
Acetaminophen is sold under the brand names Paracetamol, Tylenol, and Panadol.
What Is Acetaminophen Used For?
Acetaminophen is used to treat fever, flu, common cold, headaches, body aches, toothaches, menstrual pain, and even arthritis pain. It is available without the need for a prescription in most parts of the world.
As of 2018, acetaminophen was the 20th most prescribed drug in the United States.
How Does Acetaminophen Work?
Acetaminophen works by changing the way the body experiences pain and increased temperature.
This drug works by blocking the release of certain chemicals that signal pain sensations to the brain. As a result, the person does not feel the intensity of pain.
Acetaminophen also communicates to the heat-regulating center of the brain and asks it to lower the body’s temperature. This helps bring down the fever.
This drug is usually available as oral pills. In some cases, it may also be administered intravenously.
Side Effects Of Acetaminophen
Most people can tolerate acetaminophen well. However, some may develop some allergic reactions.
- Swelling of lips, tongue, and throat
- Itching
- Breathing difficulties
- Hives
Some studies report that the use of acetaminophen during pregnancy increases the risk of childhood asthma in babies.
Acetaminophen overdose can lead to severe liver damage. Here are some of the symptoms of Acetaminophen overdose:
- Yellowing of skin
- Abdominal pain
- Nausea and vomiting
- Dark-colored urine and stools
- Fatigue and loss of appetite
Interactions With Other Drugs
Acetaminophen can interact with many other drugs and can cause increased side effects or nullify the effects of the drugs. Make sure you notify your doctor if you use the below medications.
- Prokinetic drugs (reduce acid reflux)
- Oral anticoagulants (prevent blood clots)
- Chloramphenicol (antibiotics)
- Antiretroviral drugs (AIDS management)
- Estrogen medications
- Cytochrome P-450 enzyme inducers
Acetaminophen: Gene-Drug Interactions
Acetaminophen And TRPV1 Gene
The TRPV1 gene contains instructions for the production of a protein called transient receptor potential cation channel subfamily V member 1. This protein helps the body sense pain.
It is activated in response to high temperature, acidic conditions, and upon consumption of certain foods like hot peppers or mustard.
Acetaminophen is converted into an intermediary metabolite called N-arachidonoylphenolamine (AM404) by the fatty acid hydrolase.
Studies show that this metabolite activates the TRPV1 protein, contributing to the pain-relieving effects of this drug.
Acetaminophen And UGT1A Gene
Glucuronidation is an essential detoxification pathway for acetaminophen clearance from the body.
The UGT1A gene (UDP glucuronosyltransferase 1 family, polypeptide A cluster gene) helps produce the UGT1A enzyme that helps in acetaminophen glucuronidation.
rs8330 is a Single Nucleotide Polymorphism or SNP in the UGT1A gene.
The G allele of this SNP is associated with increased acetaminophen glucuronidation and a lower risk of acetaminophen overdose.
| Genotype | Implications |
| GG | Very high acetaminophen glucuronidation activity and very low risk of acetaminophen overdose |
| CG | Moderately high acetaminophen glucuronidation activity and lesser risk of acetaminophen overdose |
| CC | Normal acetaminophen glucuronidation activity and a normal risk of acetaminophen overdose |
Acetaminophen And OPRM1 Gene
The OPRM1 gene (opioid receptor mu 1 gene) helps produce the mu (μ) opioid receptor protein. This protein is a part of the opioid system in the body that regulates pain.
rs1977791 is an SNP in the OPRM1 gene. People with the G allele of this SNP require a higher dose of medication for pain relief compared to the A allele carriers.
About 19% of the global population has this minor G allele.
| Allele | Implications |
| G | Require higher doses of acetaminophen for pain relief |
| A | Require normal doses of acetaminophen for pain relief |
Recommendations To Use Acetaminophen
Dosage Limits
According to the Food and Drug Administration (FDA), adults should not consume more than 4g of acetaminophen in a day or 325 mg/dose. For children younger than 12, the recommended dosage limit per day is 75mg/kg of body weight.
Check For Allergy Symptoms
If you are consuming acetaminophen for the first time, carefully watch out for allergy symptoms like shortness of breath, itching, hives, and swelling.
Dosage During Pregnancy
Acetaminophen is usually safe for pregnant and breastfeeding women. However, it is always safer to inform your doctor about your pregnancy.
Dosage With Existing Liver Disease
Acetaminophen overdose can cause dangerous side effects in people with existing liver problems. Talk to your doctor before consuming the drug.
Usage In Children Younger Than Two
It may not be safe to use acetaminophen in combination with allergy, cold, and cough medications in children younger than two. Do not combine medications unless instructed by the pediatrician.
Genetic Testing
Genetic testing will help understand an individual’s response to acetaminophen and give insights on how quickly the drug is cleared from the body and dosages that may lead to toxicity.
Genetic testing can make dosage planning more precise and customized to a person’s genetic changes.
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Summary
- Acetaminophen is a pain-relieving and fever-reducing drug available in common brand names like Paracetamol, Tylenol, and Panadol.
- Acetaminophen works by changing the way the body experiences high temperature and pain.
- The side effects of acetaminophen include allergic reactions and liver damage. Acetaminophen use during pregnancy can increase the risk of childhood asthma in babies.
- Changes in TRPV1 and UGT1A genes can alter the pain-relieving effects of acetaminophen.
- Changes in the OPRM1 gene can alter the risk of acetaminophen overdose.
- Acetaminophen overdose can lead to liver failure. You have to be cautious when you consume the drug while pregnant or with existing liver diseases.
- Genetic testing will help plan the exact dosage of acetaminophen based on individual gene changes.
References
- https://medlineplus.gov/druginfo/meds/a681004.html
- https://www.medicinenet.com/acetaminophen/article.htm#what_is_acetaminophen_how_does_it_work_mechanism_of_action
- https://www.drugs.com/acetaminophen.html
- https://en.wikipedia.org/wiki/Paracetamol
- https://www.healthline.com/health/pain-relief/acetaminophen-tylenol-side-effects#side-effects
- https://pubmed.ncbi.nlm.nih.gov/21338428/
- https://pubmed.ncbi.nlm.nih.gov/15662293/
- https://www.medscape.com/answers/820200-27207/what-are-the-recommended-maximum-daily-dosages-of-acetaminophen-in-adults-and-children
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-prescription-acetaminophen-products-be-limited-325-mg-dosage-unit
