Pathways

Salbutamol is a beta-2 adrenergic receptor agonist used to treat asthma, bronchitis, COPD, as well as prevent exercise induced bronchospasms. It can be found under the brand names Airomir, Combivent, Proair, Proventil, Ventolin, and Xopenex. Salbutamol is a short-acting, selective beta2-adrenergic receptor agonist used in the treatment of asthma and COPD. It is 29 times more selective for beta2 receptors than beta1 receptors giving it higher specificity for pulmonary beta receptors versus beta1-adrenergic receptors located in the heart. Salbutamol is formulated as a racemic mixture of the R- and S-isomers. The R-isomer has 150 times greater affinity for the beta2-receptor than the S-isomer and the S-isomer has been associated with toxicity. This lead to the development of levalbuterol, the single R-isomer of salbutamol. However, the high cost of levalbuterol compared to salbutamol has deterred wide-spread use of this enantiomerically pure version of the drug. Salbutamol is generally used for acute episodes of bronchospasm caused by bronchial asthma, chronic bronchitis and other chronic bronchopulmonary disorders such as chronic obstructive pulmonary disorder (COPD). It is also used prophylactically for exercise-induced asthma. Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-3′,5′-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Salbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Salbutamol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.

Salbutamol is a selective beta-2 selective adrenergic receptor agonist drug used for the symptomatic relief and prevention of bronchospasm due to bronchial asthma, chronic bronchitis, reversible obstructive airway disease, and other chronic bronchopulmonary disorders in which bronchospasm is a complicating factor, and/or the acute prophylaxis against exercise-induced bronchospasm and other stimuli known to induce bronchospasm. It administered orally or via inhalation and is short acting. It targets the bronchiole smooth muscle where it aims to produce relaxation of these muscles to allow for greater airflow into the lungs. Activation of beta-2 adrenergic receptor by salbutamol activates the Gs signaling pathway. This involves the activation of adenylyl cyclase, which convert ATP to cAMP. This results in high levels of cAMP in the cytosol, which leads to activation of protein kinase A (PKA). For muscle contraction to occur, myosin light chain kinase (MLCK) must phosphorylate myosin light chain. This phosphorylated myosin light chain interacts with actin to produce muscle contraction. MLCK can be activated by a calcium-calmodulin complex. On the other hand, myosin light chain phosphorylase catalyzes the dephosphorylation of the phosphorylated myosin light chain, thus causing relaxation. PKA inactivates the enzyme MLCK, preventing it from phosphorylating myosin light chain. PKA may also perform phosphorylation of intracellular substrates, for example, Gq-coupled receptors, leading to a cascade of intracellular signals which reduce intracellular Ca2+, and therefore reduce activation of the MLCK present in the cytosol. These two mechanisms result in inactivation/reduced activation of MLCK, and as a result, muscle contraction is inhibited and since the dephosphorylated myosin light chain kinase accumulates rather than the phosphorylated myosin light chain kinase, muscle relaxation is enhanced. This allows for greater airflow and is beneficial in conditions like asthma where the individual experiences bronchospasm. Side effects of salbutamol include tremors, nervousness, insomnia, nausea and vomiting, fever, bronchospasm, headache, dizziness, cough, allergic reactions, increased appetite, urinary tract infections, dry mouth, gas, pain, otitis media, epistaxis, fast or irregular heartbeat, sweating.

Metabolites of Salbutamol are predicted with biotransformer.

Metabolites of Salicylamide are predicted with biotransformer.

Salicylate-sodium (also named salsonin or clin) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used for relieving pain and reducing fever. Salicylate-sodium can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of salicylate-sodium.

Salicylate-sodium is an NSAID which 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. Salicylate-sodium 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 salicylate-sodium decreases PGE2 in the CNS, it has an antipyretic effect. Antipyretic effects results in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.