Ace
Pharmacology
| Summary | Paracetamol is a commonly used medicine that can help treat pain and reduce a high temperature (fever). It’s typically used to relieve mild or moderate pain, such as headaches, toothache or sprains, and reduce fevers caused by illnesses such as colds and flu | |
| Brand Names | Napa, Ace, Tamen, Fast, Renova, Reset etc. | |
| Generic Name | Paracetamol | |
| Structure |  | |
| Synonyms | Acenol, Acetaminofén, Acetaminophen, Acétaminophène, APAP, Paracetamol, Paracétamol, Paracetamolum | |
| Chemical Formula | C8H9NO2 | |
| FDA Approved | Yes | |
Therapeutic Class | Non opioid analgesics | |
| Type | Small molecule |
Indication
Acetaminophen is a widely used over-the-counter medication for pain relief and fever reduction. It is often prescribed for mild to moderate pain, such as headaches, muscle aches, toothaches, and menstrual cramps. Acetaminophen works by inhibiting the production of prostaglandins, chemicals in the brain that cause pain and fever. It is generally considered safe when taken as directed, but excessive doses can lead to liver damage. It should be used cautiously in individuals with liver disease or alcohol dependence. Always follow the recommended dosage and consult a healthcare professional for appropriate use, especially in children or during pregnancy.
Contraindications
Allergy: Individuals with a known hypersensitivity to acetaminophen should avoid its use.
Liver Disease: Patients with severe liver disease, including cirrhosis or active liver failure, should avoid acetaminophen due to the risk of exacerbating liver damage.
Alcohol: Consumption of alcohol while taking acetaminophen increases the risk of liver damage and should be avoided.
Medication Interactions: Acetaminophen can interact with certain medications, including blood thinners (e.g., warfarin) and other drugs metabolized by the liver. Consultation with a healthcare provider is essential before using acetaminophen alongside other medications.
G6PD Deficiency: Acetaminophen may cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Caution is advised in these individuals.
Pregnancy and Breastfeeding: While acetaminophen is generally considered safe during pregnancy and breastfeeding when used at recommended doses, it is important to consult a healthcare professional before use to weigh potential risks and benefits.
Children: Dosage adjustments are necessary for children, and specific pediatric formulations should be used according to age and weight. Always follow pediatric dosing guidelines and consult a healthcare provider for proper administration.
Pharmacodynamics
Acetaminophen’s pharmacodynamics involve inhibiting the enzyme cyclooxygenase (COX), particularly COX-2, reducing prostaglandin synthesis in the central nervous system (CNS) and peripheral tissues. This action mitigates pain and lowers fever by modulating pain perception and temperature regulation. Unlike nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen has minimal anti-inflammatory effects, focusing more on analgesia and antipyresis. Its precise mechanism isn’t fully elucidated, but it’s believed to involve endocannabinoid system modulation, particularly cannabinoid receptor type 1 (CB1), within the CNS. Upon oral administration, acetaminophen is rapidly absorbed, reaching peak plasma concentrations within 30-60 minutes. Metabolism predominantly occurs in the liver via glucuronidation and sulfation, forming inactive metabolites excreted in urine. Its pharmacological profile makes it effective for mild to moderate pain relief and fever reduction, while its distinct mechanism and reduced gastrointestinal side effects compared to NSAIDs contribute to its widespread use. However, caution is warranted, especially in liver-compromised individuals, emphasizing the importance of appropriate dosing and monitoring.
Absorption
Acetaminophen is rapidly absorbed after oral administration, with peak plasma concentrations typically reached within 30 to 60 minutes. Its absorption primarily occurs in the small intestine, where it quickly enters the bloodstream. Absorption can be affected by factors such as gastric emptying time and the presence of food in the stomach. Although bioavailability is high (approximately 70-90%), it may vary between individuals due to genetic differences and other factors. Once absorbed, acetaminophen is distributed widely throughout the body, crossing the blood-brain barrier to exert its pharmacological effects centrally. Overall, its rapid and efficient absorption contributes to its efficacy as a pain reliever and fever reducer.
Distribution
Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Acetaminophen appears to be widely distributed throughout most body tissues except in fat.
Metabolism
Acetaminophen undergoes hepatic metabolism primarily via glucuronidation (45%-55%) and sulfation (30%-45%), forming inactive metabolites. A small portion (less than 5%) undergoes cytochrome P450-mediated oxidation to a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which, when accumulated, can lead to hepatotoxicity. This is mitigated by conjugation with glutathione.
Route of Elimination
Acetaminophen is primarily eliminated from the body through hepatic metabolism, with the majority of metabolites excreted in the urine (about 80% to 90%). Glucuronidation and sulfation in the liver convert acetaminophen into inactive metabolites, which are then excreted via the kidneys. A small portion (less than 5%) is excreted unchanged in the urine. Additionally, a minor fraction of acetaminophen and its metabolites may be excreted in feces and exhaled air. Overall, renal excretion is the main route of elimination for acetaminophen and its metabolites.
Clearance
Acetaminophen clearance primarily occurs via hepatic metabolism, with the liver being the main site of biotransformation. The clearance rate is influenced by factors such as liver function, age, and concomitant medications. In healthy adults, the clearance of acetaminophen is typically around 15 to 30 mL/min/kg. However, in individuals with liver impairment or reduced hepatic function, clearance may be significantly decreased, leading to a longer half-life and increased risk of toxicity. Renal impairment can also affect clearance to a lesser extent, as a small portion of the drug and its metabolites are excreted unchanged in the urine. Monitoring of liver function and dosage adjustments are essential in individuals with hepatic impairment to prevent adverse effects.
Adverse Effects
Acetaminophen is generally considered safe when taken at recommended doses; however, misuse or overdose can lead to adverse effects, particularly hepatotoxicity. Excessive consumption can overwhelm the liver’s detoxification mechanisms, leading to liver damage, liver failure, and even death. Chronic high-dose use may also contribute to kidney damage. Allergic reactions such as skin rash or swelling may occur, although these are rare. Long-term use of acetaminophen has been associated with an increased risk of gastrointestinal bleeding, although less so than nonsteroidal anti-inflammatory drugs (NSAIDs). Additionally, combining acetaminophen with alcohol can increase the risk of liver toxicity. It’s important to adhere to recommended dosages and seek medical attention if adverse effects occur.
Adverse Effects
Acetaminophen is generally considered safe when taken at recommended doses; however, misuse or overdose can lead to adverse effects, particularly hepatotoxicity. Excessive consumption can overwhelm the liver’s detoxification mechanisms, leading to liver damage, liver failure, and even death. Chronic high-dose use may also contribute to kidney damage. Allergic reactions such as skin rash or swelling may occur, although these are rare. Long-term use of acetaminophen has been associated with an increased risk of gastrointestinal bleeding, although less so than nonsteroidal anti-inflammatory drugs (NSAIDs). Additionally, combining acetaminophen with alcohol can increase the risk of liver toxicity. It’s important to adhere to recommended dosages and seek medical attention if adverse effects occur.
Toxicity
Acetaminophen toxicity, often due to overdose, can result in severe liver damage and even liver failure, which can be life-threatening. Overdosing overwhelms the liver’s capacity to metabolize the drug, leading to the formation of toxic metabolites, notably N-acetyl-p-benzoquinone imine (NAPQI). NAPQI depletes glutathione stores, causing oxidative stress and hepatocellular injury. Symptoms of acetaminophen toxicity may not be immediately apparent but can progress to nausea, vomiting, abdominal pain, and jaundice. In severe cases, acute liver failure can develop, potentially necessitating liver transplantation or resulting in death. Prompt medical intervention, including administration of the antidote N-acetylcysteine, is crucial in mitigating liver damage and improving outcomes. Preventing acetaminophen overdose through adherence to recommended dosages and avoidance of alcohol consumption while taking the drug is essential.
