11 -Leukotrienes, mechanism

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

Cells respond to some extracellular factors such as leukotriene B (Ford-Hutchin-son et al., 1980) by increasing the locomotion rate in an undirected manner as opposed to chemotaxis. This mechanism, known as chemokinesis, is likely on purely statistical grounds to result in cells accumulating at the site of origin of this stimulus (Wilkinson, 1987). The differentiation of factors that are chemotactic from chemokinetic responses can be difficult, but this has been greatly facilitated using the Boyden chamber (Lackie, 1986). 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

K. R. and Roberts, L.J. (1990). Formation of unique biologically active prostaglandins in vivo by a non-cyclooxygenase free radical catalyzed mechanism. Adv. Prostagland. Thromboxanes Leukotriene Res. 21, 125-128. 

Although there are data on the variability of the treatment response for each of these classes of agents, there are no systematic studies on the reasons for variance in the treatment response to steroids or theophylline. Therefore, this chapter will focus on the specific pharmacogenomics of /1-agonists and inhibitors of the cysteinyl-leukotriene pathway [18, 30] and on general considerations related to pharmacogenomic mechanisms. 

The answer is b. (Hardman, p 1061.) Sulfasalazine consists of sul-fapyridine with 5-aminosalicylic acid linked by an azo- bond. This bond is broken by bacteria that release the salicylic acid, which is believed to be the active agent. Sulfa drugs or salicylic acid used alone is not as effective. The mechanism of action is unknown, but it is believed to be protective action on the mucosa by inhibition of the synthesis of prostaglandins and leukotrienes. 

Stimulation of free nerve endings known as nociceptors is the first step leading to the sensation of pain. These receptors are found in both somatic and visceral structures and are activated by mechanical, thermal, and chemical factors. Release of bradykinins, K1, prostaglandins, histamine, leukotrienes, serotonin, and substance P may sensitize and/or activate nociceptors. Receptor activation leads to action potentials that are transmitted along afferent nerve fibers to the spinal cord. 

McLeish, K. R., Gierschik, P., Schepers, T., Sidiropoulos, D., Jakobs, K. H. (1989). Evidence that activation of a common G-protein by receptors for leukotriene B4 and IV-formylmethionine-leucyl-phenylalanine in HL-60 cells occurs by different mechanisms. Biochem. J. 260, 427-434. 

In addition to mechanical and thermal stimulation, there are a number of endogenous chemicals that activate or sensitize primary afferents. These include K+, serotonin, bradykinin, histamine, prostaglandins, leukotrienes, and neurokinins such as substance P. 

Cromoglycate and nedocromil are known to stabilize the outer cell membrane of mast cells and thereby inhibiting the release of histamine and leukotrienes. Their antiallergic effect might be due to more than one mechanism, for example by additionally reducing the sensitivity of inflammatory cells towards histamine. 

Zileuton Mechanisms 5-Upogenase inhibition or leukotrien receptor antagonist Elevation of liver enzymes... 

Until the late 1990s, nearly 3 decades had passed since the introduction of a truly new class of antiasthma drugs having a novel mechanism of action. This situation changed with the introduction of zafirlukast (Accolate) and montelukast (Singulair), cysteinyl leukotriene (CysLT)... 

Parthenolide inhibits serotonin release, an action that is thought to be a likely source of its effectiveness in migraine. Extracts have also been shown to reduce the production of prostaglandins (another possible mechanism) and leukotrienes. Interestingly, melatonin has been identified in feverfew, a possibly significant observation, since chronic migraines have been associated with low melatonin levels. 

Mechanism of Action An antiasthmatic and antiallergic agent that prevents mast cell release of histamine, leukotrienes, and slow-reacting substances of anaphylaxis by inhibiting degranulation after contact with antigens. Therapeutic Effect Helps prevent symptoms of asthma, allergic rhinitis, mastocytosis, and exercise-induced bron-chospasm. 

Mechanism of Action An antiasthmatic that binds to cysteinyl leukotriene receptors, inhibiting the effects of leukof rienes on bronchial smooth muscle. Therapeutic Effect Decreases bronchoconstriction, vascular permeability, mucosal edema, and mucus production. 

Mechanism of Action A mast cell stabilizer that prevents the activation and release of inflammatory mediators, such as histamine, leukotrienes, mast cells, eosinophils, andmonocytes.T herapeuticEffect Prevents both early and late asthmatic responses. Pharmacokinetics The extent of absorption is 7% to 9% of a single inhaled dose of 3.5 to 4 mg and 17% of multiple inhaled doses, with absorption largely from the respiratory tract. Although most of the inhaled dose is subsequently swallowed, only 2% to 3% is absorbed from the G1 tract. Less than 4% of the total dose is systemically absorbed following multiple doses of ophthalmic solution. Protein binding 89%. Not metabolized. Excreted in urine. Half-life 1.5-3.3 hr. 

Mechanism of Action An antiasthmaticthat binds to leukotriene receptors, inhibiting... 

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