Pathways

Aspirin (acetylsalicylic acid) is an NSAID used to treat pain, fever, inflammation, migraines, and reducing the risk of major adverse cardiovascular events. Aspirin possesses anti-inflammatory, analgesic and antipyretic activity. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Aspirin inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because aspirin decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects results in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

Acetylsalicylic acid, also known as ASA or aspirin, belongs to a class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs). In addition to its anti-inflammatory properties, aspirin also acts as an analgesic, antipyretic and antithrombotic agent. Like most other NSAIDs, aspirin exerts its therapeutic effects by inhibiting prostaglandin G/H synthase 1 and 2, better known as cyclooxygenase-1 and -2 or simply COX-1 and -2. COX-1 and -2 catalyze the conversion of arachidonic acid to prostaglandin G2 and prostaglandin G2 to prostaglandin H2. Prostaglandin H2 is the precursor to a number of other prostaglandins, such as prostaglandin E2, involved in pain, fever and inflammation. The antipyretic properties of aspirin arise from inhibition of prostaglandin E2 synthesis in the preoptic region of the hypothalamus. Interference with adhesion and migration of granulocytes, polymorphonuclear leukocytes and macrophages at sites of inflammation account for its anti-inflammatory effects. The analgesic effects of aspirin likely occur due to peripheral action at the site of injury and possibly within the CNS. Aspirin is unique from other NSAIDs in that it is an irreversible COX inhibitor. Aspirin irreversibly acetylates a serine side chain of COX rendering the enzyme inactive. Enzyme activity can only be regained by production of more cyclooxygenase. This unique property of aspirin and its higher selectivity for COX-1 over COX-2 makes it an effective antiplatelet agent. Platelets contain COX-1, a key enzyme in the production thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation. Since platelets lack the ability to make more enzyme, TXA2 production is inhibited for the lifetime of the platelet (approximately 8 – 12 days). Aspirin is commonly used at low doses to prevent cardiovascular events such as strokes and heart attacks. At higher doses, aspirin may be used as an analgesic, anti-inflammatory and antipyretic. Aspirin may cause gastric irritation and bleeding by inhibiting the synthesis of prostaglandins that enhance and maintain the protective gastric mucous layer.

Acetylene is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Acetylene passes through the liver and is then excreted from the body mainly through the kidney.

Metabolites of Acetyldigitoxin are predicted with biotransformer.

Acetylcysteine is a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose. A number of possible mechanisms for the mucolytic activity of acetylcysteine have been proposed. Acetylcysteine's sulfhydryl groups may hydrolize disulfide bonds within mucin, breaking down the oligomers, and making the mucin less viscous Acetaminophen (APAP) is metabolized in 3 main ways: glucuronidation, sulfation and oxidation. Glucuronidation and sulfation of acetaminophen produces non-toxic acetaminophen conjugates (APAP-glucuronide and APAP-sulfate). In the case of acetaminophen overdoses, a portion of the drug is metabolized by CYP2E1 to form the potentially toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The amount of NAPQI produced in an overdose saturates and depletes glutathione stores. Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation. Acetylcysteine can also provide sulfur for the sulfate conjugation of acetaminophen. Therefore, acetylcysteine aims to prevent formation of toxic NAPQI and detoxify NAPQI that has already been formed. NAPQI can cause mitochondrial dysfunction and leading to necrotic cell death. Acetylcysteine may prevent cellular toxicity by increasing oxygen delivery to tissues, increasing mitochondrial ATP production, and altering the microvascular tone to increase the blood flow and oxygen delivery to the liver and other vital organs. Oral NAC may cause nausea, vomiting, diarrhea, flatus, and gastroesophageal reflux. IV NAC can cause rate related anaphylactoid reactions in up to 18% of patients, which is not an issue with the oral route. Most of the anaphylactoid reactions are mild (6%) or moderate (10%) with severe reactions like bronchospasm and hypotension rare at 1%.