254
10.7.3 Leukotriene Inhibitors
Leukotrienes are fatty acid-derived proinflammatory molecules released in response
to inflammatory stimuli from mast cells, basophils, and eosinophils. They trigger
airway constriction, mucus production, and swelling and inflammation in the lungs,
and mediate allergic and asthmatic complications, and also play immune- modulating
functions. Thus, leukotriene modifiers or blockers are used to inactivate leukotrienemediated proinflammatory activities and thereby ameliorate the hyperimmune reactions associated with hypersensitive and autoimmune basis of development and
progression (Chagnon et al. 1985). Leukotriene inhibitors are effective in treating
allergic and asthmatic complications. So leukotriene blocking has been regarded as
an effective therapeutic strategy against allergic reaction (Garcia-Marcos and
Schuster 2001; Kemp 2003). This can be achieved by two approaches: either targeting leukotriene receptors or by inhibiting the biosynthesis of leukotriene such as
5-lipoxygenase inhibitor. Leukotriene modifiers are usually used to treat and prevent chronic asthma and allergic rhinitis along with corticosteroids for the best
result. Leukotriene receptor antagonists (LTRAs) are a class of nonsteroidal oral
medication. LTRAs are considered as anti-inflammatory agents that prevent bronchoconstriction, thereby inhibiting inflammation in the airways (Garcia-Marcos and
Schuster 2001; Montuschi et al. 2006). Leukotriene inhibitors can potentially reduce
hyperimmune response following allergic reactions and thus implemented for treating atopic dermatitis, aspirin-induced asthma, and chronic idiopathic urticaria.
Leukotriene inhibitors approved for clinical use are Montelukast, Zafirlukast,
and Zileuton. Montelukast and Zafirlukast are leukotriene receptor antagonists and
Zileuton is a 5-LOX inhibitor. Montelukast is used for treating seasonal allergy by
inhibiting LTC4, LTD4, and LTE4 (Garcia-Marcos and Schuster 2001; Kemp 2003).
Zafirlukast is a peptide inhibitor against leukotriene receptor and can prevent
smooth-muscle constriction. It is generally prescribed to treat different levels of
asthma and allergic rhinitis in patients who are above seven years old. Other leukotriene receptor antagonists developed include Verlukast and Pranlukast, which are
under investigation and development. Zileuton is a 5-LOX inhibitor that inhibits the
synthesis of LTA4, LTC4, LTD4, and LTE4 and is used to treat chronic asthma in
adolescents (Piatti et al. 2003). Other 5-LOX inhibitors include ZD2138 and
A-79175. Compared to the effectiveness of these inhibitors against asthma, leukotrienes are less effective over the inhaled corticosteroids. Leukotriene inhibitors are
thus prescribed along with inhaled corticosteroids for control of mild to moderate,
persistent asthma for better efficacy. Leukotriene antagonists help when used with
β2 agonist drugs and are found promising in aspirin-sensitive asthma patients.
Leukotriene inhibitors are also found promising for esophagitis. Montelukast has
been used to successfully treat a chronic inflammation of the bladder as well.
Leukotriene antagonists are the only class of asthma drugs with bronchoconstrictive
and anti-inflammatory potential. Some of the clinically relevant leukotrienemodifying drugs are summarized in Table 10.3.
B.C. Bhavya and M. Haridas
10.7.3 Leukotriene Inhibitors
Leukotrienes are fatty acid-derived proinflammatory molecules released in response
to inflammatory stimuli from mast cells, basophils, and eosinophils. They trigger
airway constriction, mucus production, and swelling and inflammation in the lungs,
and mediate allergic and asthmatic complications, and also play immune- modulating
functions. Thus, leukotriene modifiers or blockers are used to inactivate leukotrienemediated proinflammatory activities and thereby ameliorate the hyperimmune reactions associated with hypersensitive and autoimmune basis of development and
progression (Chagnon et al. 1985). Leukotriene inhibitors are effective in treating
allergic and asthmatic complications. So leukotriene blocking has been regarded as
an effective therapeutic strategy against allergic reaction (Garcia-Marcos and
Schuster 2001; Kemp 2003). This can be achieved by two approaches: either targeting leukotriene receptors or by inhibiting the biosynthesis of leukotriene such as
5-lipoxygenase inhibitor. Leukotriene modifiers are usually used to treat and prevent chronic asthma and allergic rhinitis along with corticosteroids for the best
result. Leukotriene receptor antagonists (LTRAs) are a class of nonsteroidal oral
medication. LTRAs are considered as anti-inflammatory agents that prevent bronchoconstriction, thereby inhibiting inflammation in the airways (Garcia-Marcos and
Schuster 2001; Montuschi et al. 2006). Leukotriene inhibitors can potentially reduce
hyperimmune response following allergic reactions and thus implemented for treating atopic dermatitis, aspirin-induced asthma, and chronic idiopathic urticaria.
Leukotriene inhibitors approved for clinical use are Montelukast, Zafirlukast,
and Zileuton. Montelukast and Zafirlukast are leukotriene receptor antagonists and
Zileuton is a 5-LOX inhibitor. Montelukast is used for treating seasonal allergy by
inhibiting LTC4, LTD4, and LTE4 (Garcia-Marcos and Schuster 2001; Kemp 2003).
Zafirlukast is a peptide inhibitor against leukotriene receptor and can prevent
smooth-muscle constriction. It is generally prescribed to treat different levels of
asthma and allergic rhinitis in patients who are above seven years old. Other leukotriene receptor antagonists developed include Verlukast and Pranlukast, which are
under investigation and development. Zileuton is a 5-LOX inhibitor that inhibits the
synthesis of LTA4, LTC4, LTD4, and LTE4 and is used to treat chronic asthma in
adolescents (Piatti et al. 2003). Other 5-LOX inhibitors include ZD2138 and
A-79175. Compared to the effectiveness of these inhibitors against asthma, leukotrienes are less effective over the inhaled corticosteroids. Leukotriene inhibitors are
thus prescribed along with inhaled corticosteroids for control of mild to moderate,
persistent asthma for better efficacy. Leukotriene antagonists help when used with
β2 agonist drugs and are found promising in aspirin-sensitive asthma patients.
Leukotriene inhibitors are also found promising for esophagitis. Montelukast has
been used to successfully treat a chronic inflammation of the bladder as well.
Leukotriene antagonists are the only class of asthma drugs with bronchoconstrictive
and anti-inflammatory potential. Some of the clinically relevant leukotrienemodifying drugs are summarized in Table 10.3.
B.C. Bhavya and M. Haridas