12.1 Mechanism of Action Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects, but the precise mechanism of action is unknown. Tretinoin is a metabolite of vitamin A that binds with high affinity to specific retinoic acid receptors located in both the cytosol and nucleus. Tretinoin activates three members of the retinoic acid (RAR) nuclear receptors (RARα , RARβ, RARγ) which act to modify gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. It has not been established whether the clinical effects of tretinoin are mediated through activation of retinoic acid receptors, and/or other mechanisms. Although the exact mode of action of tretinoin in acne treatment is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
12.1 Mechanism of Action Like other topical corticosteroids, clobetasol propionate shampoo, 0.05%, has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 .
In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins.[A6505] Erythromycin acts by inhibition of protein synthesis by binding to the 23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible bacterial organisms. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.[L7261,A14179] This results in the control of various bacterial infections.[A174193,L7261] The strong affinity of macrolides, including erythromycin, for bacterial ribosomes, supports their broad‐spectrum antibacterial activities.[A174193]
Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.
Lidocaine is a local anesthetic of the amide type [F4349, L5930, L5948]. It is used to provide local anesthesia by nerve blockade at various sites in the body [F4349, L5930, L5948]. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action [F4349, L5930, L5948]. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes [F4349, L5930, L5948]. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions [F4349, L5930, L5948]. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization [F4349, L5930, L5948]. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential [F4349, L5930, L5948]. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place [F4349, L5930, L5948].
In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system [F4349, L5930, L5948]. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction [F4349, L5930, L5948].
prednisolone sodium phosphate
12.1 Mechanism of Action Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisolone which are due to its glucocorticoid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion. Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited. Prednisolone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisolone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.
12.1 Mechanism of Action Naturally occurring corticosteroids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, such as prednisone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Corticosteroids, such as prednisone, cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli. Prednisone is a synthetic adrenocortical steroid drug with predominantly corticosteroid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisone which are due to its corticosteroid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion. Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited. Prednisone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.
12.1 Mechanism of Action Remibrutinib is an oral, small molecule kinase inhibitor that inhibits Bruton’s tyrosine kinase (BTK). BTK is an intracellular protein expressed in mast cells, basophils, B cells, macrophages, and thrombocytes. BTK is involved in intracellular signaling via Fc epsilon receptor-1 (FcεR1), Fc gamma receptors (FcγR), and the B cell antigen receptor (BCR). Remibrutinib also inhibits the BTK-related kinases tec protein tyrosine kinase (TEC) and BMX non-receptor tyrosine kinase (BMX). Remibrutinib inhibits mast cell and basophil degranulation, including release of histamine and other proinflammatory mediators, mediated by pathogenic IgE or IgG directed against the FcεR1 or IgE.
Salicylic acid directly and reversibly inhibits COX-1 and COX-2 to decrease conversion of arachidonic acid to precursors of prostaglandins and thromboxanes.[A33150, A274656] Salicylate's use in rheumatic diseases is due to it's analgesic and anti-inflammatory activity. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. Salicylic acid allows cells of the epidermis to more readily slough off. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid competitively inhibits oxidation of uridine-5-diphosphoglucose (UDPG) with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of the glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to a phenolic acceptor. Inhibition of mucopoly saccharide synthesis is likely responsible for the slowing of wound healing with salicylates.