OTC Analgesics: Acetaminophen

Kristen Mouser, Student Pharmacist

History of Use and Abuse

KristenMouser

Acetaminophen was approved as an over-the-counter (OTC) analgesicby the FDA in 1955.1 It is currently the most common drug ingredient, being incorporated into over 600 different medications.2 With it being used in so many patients at an uncontrolled rate, comes a high amount of overdose A study done in 2021 reveals that around 56000 emergency room visits and 26000 hospitalizationsare due to acetaminophenoverdoses each year.3

The use of the medication continues to grow, and overuse tends to occur due to self-treating and the addition of OTC acetaminophen to an already prescribed medication with acetaminophen in it.4 A research article evaluating the use of nonprescription analgesics, reveals that in a study of 39767 people 38.3% reported havingused acetaminophen more than once a week for the past month.4 Then even more specifically, 10.6% of participants reported utilizing it at least once daily in the past month.4 These results reveal the frequency of acetaminophenuse in the population.

The majority of patients who reported usinghigh amounts of acetaminophen, also reported having intermittent opioid use and chronicpain (71.5%)

4Chronicpain is defined as pain that lasts more than 3 months.5 Patients experiencingthis use analgesics to make themselves more comfortable, but the problem is developingtolerance and dependence, which ultimately can lead to an increased risk of overdose. Tolerance is establishedfrom the frequent exposure to a medication where they begin developinga resistance to it, meaningthey will need a higher dose to elicit the same response.6 Then dependence is also due to the frequent use of a medication where they grow accustomed to it being in the body.6 This can create an environment where the body wont function without the medication and even if the pain resolves, the patient will feel the need to continue utilizingit.

An acetaminophen addictionis not usually due to the same reasons as many other drugs. Unlike opioids or illicit substances there is no “high” or sense of euphoria. However, a few studies show that it may reduce emotional response.7 This indicates that those who use acetaminophen at a higher than recommended level may have reduced neural responses and has shown a decrease in both positive and negative emotions.7

Other Names for Acetaminophen

- Pain meds

- Liver killers

- Painkillers

Pharmacology/ Drug Effects https://www.flaticon.com/free-icon/pain_387630

Acetaminophen is used as an analgesicand antipyretic, but unlike NSAIDs it does not show peripheral anti inflammatory effects. The mechanism of action is still unknown;however, it is thought to work by inhibiting the COX pathway which blocks prostaglandinsecretion in the central nervous system.8 By acting on the hypothalamus the medicationis able to play a role on temperature and reduce fever. Then there is thought to be an antinociceptive effect that occurs by activating the descendingserotonergicpathways.9 This is the response mechanism of sensory neurons to toxicities, injuries, or pain.9 With this occurring in the central nervous system it is possible this is also the cause of the reduced emotional response.

Drug interactions/ toxicology

Acetaminophendoesn’t have any severe interactions with other medications. However, it does have drug disease interactions with alcoholism and liver disease.10 Elevated and sometimes prescribed amount of acetaminophencan cause hepatotoxicity indicated by elevated serum aminotransferase.11 When there is an overdose, it can result in jaundice, confusion, acute liver injury and failure that can lead to death or need for a liver transplant. 11

Professional opinion

I would recommend Acetaminophen as a short term, as needed therapy for pain and fever management. I would consider it to be safe and have a low chance of addiction. The main concern is it is easy to overdose, patients need to be properly educated on maximum dosingand the large incorporation of acetaminophen into combinationproducts. ~ K. Mouser

References

1. Leichty J. Selection of AcetaminophenforConsiderationfor Listing . US FDA. https://oehha.ca.gov/media/dockets/19653/19710u.s._food_and_drug_administration_fda/fda_comments_notice_of_avai lability_of_hazard_identification_materials_for_acetaminophen_11420 19.pdf.Published 2019.Accessed October 10, 2022.

2. Acetaminophen.ConsumerHealthcareProductsAssociation. https://www.chpa.org/our-issues/otcmedicines/acetaminophen#:~:text=Acetaminophen%20is%20the%20m ost%20common,%2C%20cold%2C%20and%20allergy%20medicines. Published 2022.Accessed October 13, 2022.

https://www.shutterstock.com/image-illustration/conceptual-image-druginducedhepatotoxicity-3d-illustration-774287005

Laws

Currently there are no laws concerning OTC acetaminophen. In the past there have been actions made to limit the amount of drug to 325mg per unit in combinationproducts.12 This is to make the product safer for patients by reducingrisk of accidental overdose. 12

Monitoring/ drug screens

Patients frequently usingacetaminophen should first be informed of the maximum daily dosage of 4 grams a day in patients with normal liver function. It is also important to monitor for signs and symptoms of hepatictoxicity.13 These include dark colored urine, light colored bowel movements, jaundice, and loss of appetite.13 If there is an overdose the serum or blood acetaminophenlevel should be obtainedafter 4 hours of ingestion.13 If the level is at or above 150 mcg/mL then begin on acetylcysteine, the medication used to manage an acute overdose.13 If the acetaminophen level remains elevated an ALT or AST will be obtained after the acetylcysteine infusion.13 Then the infusion will continue until an ALT of less than 50% and an acetaminophenvalue of 10 mcg/mL.13

3. WhatHappensif youTakeToo MuchAcetaminophen?Piedmont Healthcare.https://www.piedmont.org/living-better/what-happens-ifyou-take-too-muchacetaminophen#:~:text=%E2%80%9CAcetaminophen%20overdose%2 0is%20one%20of,patients%20aged%2015%20to%2024.%E2%80%9D. Accessed October 13, 2022.

4. Dale, O., Borchgrevink, P.C., Fredheim, O.M.S. et al. Prevalence of use of non-prescription analgesics in theNorwegian HUNT3 population: Impactof gender, age, exercise andprescription of opioids. BMC Public Health15, 461 (2015). https://doi.org/10.1186/s12889-0151774-6

5. Commonlyusedterms. Centers for Disease ControlandPrevention. https://www.cdc.gov/opioids/basics/terms.html.Published 2021. Accessed October 13, 2022.

6. Acetaminophen -over-the-counter painmedicationabuse.New Beginnings Drug Rehab. https://www.newbeginningsdrugrehab.org/acetaminophen.Published 2019.Accessed October 13, 2022.

7. Grey H. Tylenol relief from emotionaldistress. Healthline. https://www.healthline.com/health-news/tylenol-relieve-hurtfeelings#May-blunt-positive-emotions,-too. Published 2017. Accessed October 13, 2022.

8. Gerriets V, Anderson J, NappeT. Acetaminophen.StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK482369/.Published 2022. Accessed October 14, 2022.

9. Dogrul A, Seyrek M, Akgul EO, CayciT, KahramanS,Bolay H. Systemic paracetamol-inducedanalgesicandantihyperalgesiceffects through activationof descendingserotonergic pathwaysinvolving spinal5-HT₇ receptors. Eur J Pharmacol.2012;677(1-3):93-101. doi:10.1016/j.ejphar.2011.12.016

10. Acetaminopheninteractionschecker.Drugs.com. https://www.drugs.com/drug-interactions/acetaminophen.html. Accessed October 13, 2022.

11. Toxic hepatitis. MayoClinic. https://www.mayoclinic.org/diseasesconditions/toxic-hepatitis/symptoms-causes/syc-20352202.Published 2022.Accessed October 13, 2022.

12. Prescription acetaminophenproductstobe limited to325 mgper dosage. U.S. FoodandDrug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drugsafety-communication-prescription-acetaminophen-products-belimited-325-mg-dosage-unit. Published 2018.Accessed October 13, 2022.

13. Tylenol® Products &ProfessionalResources. TYLENOL® Professional. https://www.tylenolprofessional.com/.Accessed October 13, 2022.

Arianna Dollinger, Student pharmacist

Pharmacology of alcohol

Alcohol binds directly to acetylcholine (ACh), serotonin, GABA, and the NMDA receptors for glutamate. GABA and glycine receptors mediate the sedative effects of alcohol. Alcohol is a dehydrating agent and disrupts the osmotic homeostasis across cell membranes.There are two main pathways for alcohol metabolism: alcohol dehydrogenase (ADH) pathway and microsomal ethanol-oxidizing system (MEOS).

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Street names

3,000 - 2,000 B.C.

Beer was made in Ancient Mesopotamia. Alcohol was used in sacrificial settings.

16th & 17th Century

Intoxication and drunkenness became a crime in the 1600s. Britain began taxing alcohol in 1643.

2,000 B.C.

The earliest vineyards were established by the Ancient Greeks and the Greek god of wine – Dionysus Alcohol was used as currency, medicine, and religious offering to the gods.

2016

488,000 adolescents (12-17) have had an alcohol use disorder. 10.9 million adults (> 26) have had an alcohol use disorder.

17th - 20th Centuries

Banning alcohol as payment resulted in extreme labor strike. By 1830, Americans consumed an average of 7.1 gallons per person each year. This equates to ~55 handles of alcohol. In 1860, the U.S. produced ~88 million gallons of liquor per year. In 1952, the American Medical Association first defined alcoholism.

Drug Interactions:

Aspirin and acetaminophen

Can cause liver damage

Antihistamines, such as diphenhydramine

Increased drowsiness, sedation, and decreased motor skills

Anticoagulants: warfarin

Acute alcohol consumption may increase anticoagulation by decreasing warfarin metabolism

Chronic alcohol consumption decreases anticoagulation by increasing warfarin metabolism

Benzodiazepines, such as alprazolam, lorazepam

Increased drowsiness, sedation, and decreased motor skills

NSAIDs: ibuprofen, naproxen

Increased risk of GI bleeding

MANY OTHERS!!

Alcohol Laws:

Minimum Legal Drinking Age (MDLA) of 21 years old in the United States.

National Highway System Designation Act of 1995 requires a zero-tolerance law prohibiting drivers < 21 from operating a motor vehicle with 0.02% BAC.

Public intoxication is a class B misdemeanor in Indiana.

References:

Monitoring/Testing

Blood alcohol concentration test: Blood test that shows blood alcohol levels up to 12 hours after drinking

Breathalyzer: Estimates blood alcohol content in deep lung air

Professional Opinion:

I believe that alcohol is okay in moderation. However, it is extremely important to be educated on its effects and interactions with other substances and medications. Alcohol is a drug and does need to be treated as such, although it is legally and socially acceptable. ~ A. Dollinger

1. Street names and nicknames for alcohol. Drug Rehab Options. Published September 28, 2022. Accessed October 13, 2022. https://rehabs.com/blog/street-names-and-nicknames-for-alcohol/.

2. The history of alcohol throughout the world. Recovery.org. Published July 18, 2022. Accessed October 13, 2022. https://recovery.org/alcohol-addiction/history/.

3. Ethanol. Uses, Interactions, Mechanism of Action. DrugBank Online. https://go.drugbank.com/drugs/DB00898. Accessed October 13, 2022.

4. Chapter 23: The alcohols. AccessMedicine. Accessed October 13, 2022. https://accessmedicine.mhmedical.com/content.aspx?bookid=2249§ionid=175218881#1148435877.

5. Weathermon R, Crabb DW. Alcohol and medications interactions. Alcohol Res Health. 1999;23(1):40-54. PMID: 10890797; PMCID: PMC6761694.

6. Minimum legal drinking age of 21 saves lives. Centers for Disease Control and Prevention. Published April 19, 2022. Accessed October 14, 2022. https://www.cdc.gov/alcohol/fact-sheets/minimum-legal-drinkingage.htm#:~:text=Minimum%20Legal%20Drinking%20Age%20(MLDA)%20laws%20specify%20the%20legal%20age,varied%2 0from%20state%20to%20state.

7. Blood alcohol level: Medlineplus medical test. MedlinePlus. Accessed October 14, 2022. https://medlineplus.gov/lab-tests/bloodalcohol-level/#:~:text=A%20blood%20alcohol%20concentration%20(BAC,of%20alcohol%20that%20you%20drank.