According to Prof. Fred Ehlert  (n.d.), pharmacology is divided into two major topics that include pharmacodynamics and pharmacokinetics. While pharmacodynamics covers how drugs produce their effects on the body, pharmacoki8netics covers how the drugs are ingested through excretion. Pharmacokinetics can further be divided into four topics that include absorption, distribution, metabolism, and excretion with the acronym, ADME.

Absorption covers how the drug enters the body and its journey  through systemic circulation subject to the  route of administration. For example, when a drug is administered orally, it travels to the intestines and diffuses across the gastrointestinal epithelium. It further diffuses into the hepatic portal vein that delivers it to the liver, where it finally gains access to the systemic circulation by diffusing into the hepatic vein. However, when a drug is administered intravenously, it enters directly into the systemic circulation thereby, circumventing the absorption phase and minimizing the impact of the first pass effect.

Metabolism of drugs is followed by the elimination or excretion of the byproducts of the metabolism also known as the metabolites. The metabolite can be processed further for absorption of the active constituents in case s such as prodrugs. According to Prof Ehlert, drug molecules are xenobiotics or foreign to the body. Hence, it’s the tendency of the body to process and eliminate foreign molecules from the body. For example, alcohol is metabolized into acetaldehyde by the enzyme, alcohol dehydrogenase or ADH in the first phase of the metabolic process, while further, broken down into acetate by the enzyme, acetaldehyde dehydrogenase for elimination (Kuhn etal, 2019). Xenobiotic metabolism, commonly converts compounds into less active forms. However, according to Prof. Ehlert, some metabolites can have have increased activity or toxicity.

The metabolism of drugs can take two phases. In then first phase, the compound undergoes enzymatic or cytochrome P450 mediated oxidation . While in second phase, conjugation with glucuronic acid is achieved. The derivative metabolite is readily eliminated in the bile. Because most drug metabolism occurs in the liver or more precisely, in the hepatic cells, metabolites produced in the hepatic cells can be transported into the bile canaliculi, from which they enter the bile duct for delivery to the intestines for excretion with feces.

Glucuronosyltransferase is the the enzyme responsible for the catalysis of glucuronidation. The metabolism of acetaminophen mainly involves sulfation and glucuronidation. Under regular dosing, the metabolite of the first phase of metabolism producing benzoquinone is  conjugated with glutathione by GST. However, in acetaminophen overdose, the tissue levels of glutathione can be depleted leading to excessive accumulation of benzoquinone , causing hepatotoxicity and liver cell death (Ehlert, n.d.). Another common name for acetaminophen is paracetamol. According to the latest report on acetaminophen or paracetamol available online, scientists have cautioned the older adult population against self-medicating with acetaminophen due to increased risks of internal bleeding, chronic kidney disease (CKD), cardiovascular disease, and hepatotoxicity (Simmons, 2025).

References

Ehlert, F. (n.d.). Script for Pharmacokinetics 1 Lecture. UC Irvine. www.uci.edu

Kuhn, C., Swartzwelder, S. , & Wilson, W. (2019). BUZZED: The Straight Facts About the Most Used and Abused Drugs From Alcohol to Ecstasy (5th ed.). W.W. Norton & Company, Inc. www.norton.com

Simmons, E. (2025). Urgent warning over paracetamol - regular use of common painkiller linked to deadly health problem. DailyMail.com Urgent warning over paracetamol - regular use of common painkiller linked to deadly health problem | Daily Mail Online