Pulmonolgy Medications part 3.pdf

P U L M O N A RY M E D I C AT I O N S PA RT 3 Debra Forzese, Pharm. D. MAST CELL STABILIZERS MAST CELL STABILIZERS Cromolyn Sodium Nebulizer solution Nedrocromil • CROMOLYN SODIUM INHALED Indications § Prophylactic use before exposure to asthma trigger such as exercise and/or allergens §...

P U L M O N A RY M E D I C AT I O N S PA RT 3 Debra Forzese, Pharm. D. MAST CELL STABILIZERS MAST CELL STABILIZERS Cromolyn Sodium Nebulizer solution Nedrocromil • CROMOLYN SODIUM INHALED Indications § Prophylactic use before exposure to asthma trigger such as exercise and/or allergens § Chronic use as a controller – alternative to glucocorticoid (requires 3 or 4 doses per day) CROMOLYN SODIUM INHALED Dosing • Adult – maximal dose is used initially • Pediatric • Renal impairment – no dose adjustment • Hepatic impairment – no dose adjustment • CROMOLYN SODIUM INHALED Mechanism of Action • Prevents release of inflammatory mediators (histamine, leukotrienes) from mast cells • Works at surface of mast cells inhibiting degranulation CROMOLYN SODIUM INHALED • Acts to prevent bronchospasm • NO bronchodilation CROMOLYN SODIUM INHALED Pharmacokinetic/Pharmacodynamic Factors • Poorly absorbed • Low toxicity CROMOLYN SODIUM INHALED Adverse Effects • Headache, diarrhea most common • Mild throat irritation • Cough • Hypersensitivity CROMOLYN SODIUM INHALED Warnings • Anaphylaxis rare • Bronchospasm with cough can occur after inhalation • Abrupt withdrawal can cause symptoms to reoccur CROMOLYN SODIUM INHALED • Drug interactions § No known significant interactions CROMOLYN SODIUM INHALED • Pregnancy – category B • Breastfeeding – drug levels in breastmilk expected to be low, experts consider use of cromolyn acceptable during breastfeeding CROMOLYN SODIUM INHALED Monitoring • Pulmonary function tests CORTICOSTEROIDS INHALED Ciclesonide (Alvesco) Fluticasone (Arnuity) INHALED CORTICOSTEROIDS Momentasone (Asmanex) Budesonide (Pulmicort) Beclomethasone (QVAR) INHALED CORTICOSTEROIDS Indications • Treatment of choice - prevents asthma exacerbations in persistent asthma • Updated guidelines recommend use for acute asthma symptoms in conjunction with beta2 agonists in adults and adolescents • Used off label to manage COPD INHALED CORTICOSTEROIDS Mechanism of Action • Reduces inflammation by decreasing formation/release of inflammatory mediators • Induces vasoconstriction • Reduces immune response, limits lung hypersensitivity INHALED CORTICOSTEROIDS Dosing • Adult – low, medium, high dose based on patient symptoms • Pediatric – concerns about side effects such as growth suppression, bruising, osteoporosis, metabolic (glucose) • Renal impairment – no dose adjustments provided in manufacturer’s labeling • Hepatic impairment – no dose adjustments provided in manufacturer’s labeling INHALED CORTICOSTEROIDS Formulations • Nebulizer solution • Metered dose inhaler • Dry powder inhaler INHALED CORTICOSTEROIDS Comparisons • Studies suggest that fluticasone and budesonide have less systemic effects • Newer agents mometasone and ciclesonide may also have less systemic effects INHALED CORTICOSTEROIDS Adverse Effects • Oral candidiasis (thrush) – drug deposited in oropharynx instead of the lungs – instruct patients to rinse mouth with water and spit after use • High doses – increase the risk of infections from immunosuppression(chickenpox, TB) • Throat irritation, sinusitis • Cough • Headache Rarely – adrenal suppression, reduced bone density, glaucoma/cataracts from long term use INHALED BUDESONIDE • Used via inhalation for acute attacks as well as prophylaxis • Can cause oropharyngeal candidiasis – prevent with use of spacer and/or gargling after use • Available as nebulizer suspension and dry powder inhaler INHALED BUDESONIDE Pharmacokinetic/Pharmacodynamic Factors • Pharmacokinetics plays a role in relation to systemic effects • Has greater first pass metabolism than beclomethasone, less likely to cause systemic effects • Peak effect (oral inhalation)- adults 10 minutes, pediatrics 15-30 minutes • Half life in adults 2-3.6 hours, pediatrics 1.5 hours INHALED BUDESONIDE Adverse Effects • Paradoxical bronchospasm • Respiratory infection, infection of oral cavity (thrush) • Glucose intolerance, hypokalemia • Infections such as chickenpox, measles, TB • Hypersensitivity • Adrenal suppression • Osteoporosis • Delayed wound healing • Reduced linear growth in pediatric patients Drug Interactions • INHALED BUDESONIDE • Strong inhibitors of CYP3A4 such as erythromycin, diltiazem, ketoconazole increase serum concentration of budesonide Tobacco smoking – diminishes therapeutic effect of budesonide INHALED BUDESONIDE • Pregnancy – budesonide one of the preferred inhaled corticosteroid agents • Breastfeeding – considered compatible INHALED BUDESONIDE Monitoring • Pulmonary function tests • Liver enzymes – especially with impairment (can accumulate) • Potassium level – especially if patient also taking diuretic CORTICOSTEROIDS SYSTEMIC CORTICOSTEROIDS SYSTEMIC • Short courses very effective for control of acute asthma symptoms • Early administration for treatment of severe asthma exacerbations is considered a standard of care • GINA guidelines recommends short term use (5-7 days) for severe acute exacerbations ORAL GLUCOCORTICOID IN ASTHMA • GINA guidelines – consider adding oral glucocorticoids for severe persistent asthma steps to optimize control of symptoms and minimize adverse effects • NAEPP updated guidelines 2020 – consider adding oral glucocorticoid for severe persistent asthma GLUCOCORTICOIDS SYSTEMIC • Less relapse with systemic steroids • Studies indicate no difference in efficacy or onset of action between oral and IV administration • Guidelines prefer oral steroid if possible • Courses over 5 days - no additional benefit GLUCOCORTICOIDS SYSTEMIC • Start systemic steroid if lack of immediate marked response to inhaled rapid onset beta2 agonist (albuterol) GLUCOCORTICOID SYSTEMIC • Systemic corticosteroid recommended for patients with asthma exacerbation that need ED treatment or hospitalization • Adults: Prednisone 40-60 mg per day for 5-7 days (with food) • Pediatrics (less than 12 years) 1-2 mg/kg/day, use solution • Dexamethasone is alternative used in pediatrics (less vomiting, longer half life) 1 GLUCOCORTICOID SYSTEMIC • Courses of steroid for < 3 weeks- no need to taper if patient also on ICS • Occasionally IM steroid at time of discharge (methylprednisolone) as effective as oral • Studies suggest short/long term oral steroids associated with an increased risk of acute and chronic complications, greater exposure leads to greater risk • Oral steroids overused for management of severe asthma GLUCOCORTICOID SYSTEMIC • IV steroids in acute asthma if lung function less than 30% predicted and in patients with no significant improvement with nebulized beta 2 agonist • Hydrocortisone used since fastest onset – switch to oral after response GLUCOCORTICOID SYSTEMIC Adverse effects • GLUCOCORTICOID SYSTEMIC • • • • • • Fluid retention Increased appetite, weight gain Osteoporosis HTN Diabetes Cataracts Psychosis LEUKOTRIENE PATHWAY INHIBITORS LEUKOTRIENE PATHWAY INHIBITORS Montelukast (Singulair) Zafirlukast (Accolate) LEUKOTRIENE PATHWAY INHIBITORS MONTELUKAST Indications • Prophylaxis, chronic treatment of asthma in adults and pediatric patients over 12 years of age • Prevention of exercise induced bronchoconstriction in adults and pediatric patients > 6 years of age MONTELUKAST Dosing • Adult – 10 mg daily in the evening; use 2 hours prior to exercise to prevent exercise induced asthma • Pediatric – not preferred • Renal impairment – no dose adjustment • Hepatic impairment – no dose adjustment MONTELUKAST Mechanism of Action • Interfere with pathway that allows mast cells, eosinophils, and basophils to release leukotriene mediators • As a result, reduces symptoms associated with inflammatory allergic component of asthma MONTELUKAST Pharmacokinetic/Pharmacodynamic Factors • Extensively metabolized • Half life 2.7 – 5.5 hours MONTELUKAST Adverse Effects • Upper respiratory infections • Fever • Headache • Pharyngitis • Cough US Boxed Warning: MONTELUKAST • Serious neuropsychiatric events reported – agitation, aggression, suicidal thoughts • Benefits may not outweigh risks in some patients • Discuss benefits/risks with patients and caregivers, advise patients/caregivers to be alert for behavior changes and discontinue montelukast if concerning behaviors develop and call provider immediately MONTELUKAST Drug Interactions • Gemfibrozil – can increase concentration of montelukast • CYP3A4 inducers – phenytoin, glucocorticoids – decrease effectiveness of montelukast MONTELUKAST • Pregnancy – may continue if patient already on montelukast but initiation during pregnancy not recommended • Breastfeeding – present in breastmilk, per manufacturer the decision to breastfeed during therapy should consider risk to infant, benefits of breastfeeding, benefits of treatment to mother MONTELUKAST Monitoring • Neuropsychiatric events