Leukotriene inhibitors + phosphodiesterase inhibitor Flashcards
Leukotriene inhibitors - 2 groups
Leukotriene receptor antagonists.
5-lipoxygenase inhibitors
Leukotriene receptor antagonists - 2 drugs
5-lipoxygenase inhibitor - 1 drugs
Leukotriene receptor antagonists - montelukast, zafirlukast.
5-lipoxygenase inhibitor - Zileuton.
Montelukast and zafirlukast - MOA
Structurally similar to cysteinyl leukotrienes. Competative inhibition of CysLT1. Inhibit early and late phases of asthma.
Do not inhibit effects of leukotriene B4.
Leukotriene receptor antagonists - adm
Oral.
Zafirlukast - 2 hours after food
Leukotriene receptor antagonists - interactions
Enhance bronchodilating effect of β2-agonitst
Zafirlukast: metabolized by P450 enzymes. Inhibits CYP2C9 (phenytoin, warfarin) and CYP3A4 (felodipine, lovastatin, triazolam)
Montelukast and zafirlukast - indications
Asthma: pt unable/unwilling to take steroids. Asthma that is not adequately controlled by steroids alone.
Allergic, aspirin-sensitive, and exercised-induced asthma.
Montelukast and zafirlukast are most effective for which pts?
Young children
Leukotriene receptor antagonists - onset
Maximal effect after weeks/months.
Leukotriene receptor antagonists - adverse effects
Rarely cause side effects.
Liver injury and failure.
Churg-Strauss syndrome (allergic granulomatous vasculitis) - if montelukast or zafirlukast replaces glucocorticoids.
Zileuton - MOA
Inhibits 5-lipoxygenase, blocking formation of all leukotrienes
Zileuton is most effective for …
Severe asthma
Zileuton - adverse effects
Flulike syndrome. Headache. Drowsiness. Dyspepsia. Hepatitis.
Zileuton - contraindications
Caution in high alcohol consumption.
Zileuton - interactions
Inhibits CYP1A3 and CYP3A4 - elevate theophylline and warfarin
Leukotriene receptor antagonist preferred in concomitant drug therapy
Montelukast.
Phosphodiesterase inhibitor - 1 drug
Roflumilast
Roflumilast - MOA
Selective inhibitor of PDE in lungs. Increases cAMP intracellularly
Roflumilast - indications
Reduce risk of COPD exacerbations in chronic bronchitis in pts with history of exacerbations.
Roflumilast - adverse effects
Diarrhea, nausea, weight loss.
Anxiety, insomnia, depression.
Roflumilast - interactions
Metabolized by CYP3A4 and CYP1A2
Roflumilast - contraind
Strong inducers (rifampin) and inhibitors (erythromycin) of CYP enzymes. Acute respiratory episodes (has no function in these cases)
Roflumilast - adm
Orally