Pulmonary System Medications Part 1 PDF

Pulmonary Medications Part 1 DEBRA FORZESE, PHARM. D. Sympathomimetic Agents • Bind to β adrenergic receptors in airway smooth muscle o Causes stimulation of adenyl cyclase o Results in formation of cAMP which promotes bronchodilation • β-2 selective agents commonly used for treatment of acute br...

Pulmonary Medications Part 1 DEBRA FORZESE, PHARM. D. Sympathomimetic Agents • Bind to β adrenergic receptors in airway smooth muscle o Causes stimulation of adenyl cyclase o Results in formation of cAMP which promotes bronchodilation • β-2 selective agents commonly used for treatment of acute bronchoconstriction, selective for airway smooth muscle • Short acting and long acting Adverse Effects beta 2 Agonists Cardiac •arrhythmias, tachycardia, chest pain •cardiomyopathy •ischemia Metabolic •hypokalemia •increase in blood sugar Musculoskeletal •Tremors Tolerance to beta agonists • Prolonged stimulation from agonists can lead to tolerance oBlunting of bronchodilatory and anti-bronchoconstrictor effects Treatment principles • Control symptoms • Minimize asthma or COPD mortality risk • Reduce exacerbations • Limit medication side effects Short Acting Beta Agonists (SABA) SABA • Mainstay treatment for asthma and COPD • SABA first line for acute asthma symptoms, long- acting muscarinic agonists in treatment of COPD • Inhalation has improved therapeutic activity with less systemic side effects SABA Albuterol (Ventolin, Proventil) Levalbuterol (Xopenex) Use of SABA • GINA guidelines – recommend against SABA monotherapy because associated with higher rate of exacerbations than inhaled corticosteroid (ICS) containing therapy oSign of good asthma control – limited/eliminated need for SABA use regularly • NHLBI 2020 guidelines –SABA can be used as needed as monotherapy for intermittent asthma, also for pretreatment of exercise induced bronchospasm SABA • Available in 3 formulations oMetered Dose Inhalers (MDI) oDry Powder Inhalers (DPI) oNebulizer solutions – vaporize dose of medication in saline solution SABA • All asthma patients should have SABA inhaler for use as needed • β2 agonists do not have anti-inflammatory effects, can’t be used as monotherapy for persistent asthma Common Problems with Asthma Medications • Poor inhaler technique • Poor medication adherence • Incorrect diagnosis of asthma • Comorbidities and complicating conditions (reflux disease, obesity, etc) • Ongoing exposure to irritants Albuterol Indication • Treatment and/or prevention of bronchospasm in asthma and other reversible obstructive airway disease (chronic bronchitis, emphysema, etc) Albuterol Dosing of metered dose inhaler (MDI), dry powder inhaler (DPI) 90 mcg/actuation • Adult – used for acute exacerbation, intermittent symptom relief, exercise induced bronchoconstriction (prevention) • Pediatric • Renal impairment – no dose adjustments • Hepatic impairment – no dose adjustments Albuterol • Mechanism of Action – binds to β2 adrenergic receptors, which results in bronchodilation oQuick onset, rapidly relax bronchial smooth muscle from trachea to bronchioles by action on the β2 receptors Albuterol Pharmacokinetic/Pharmacodynamic Factors • Onset of action - 5-8 minutes for MDI, 5-6 minutes for DPI, nebulizer solution (<5 minutes) • Duration of action – 4-6 hours MDI, 2 hours DPI, nebulizer solution 3-6 hours • Excretion – urine 80-100%, feces < 20% Albuterol Adverse Effects • Tremors (increases with age) • Nervousness • Cardiac - palpitations, tachycardia, chest pain, hypo/hypertension • Metabolic – hypokalemia, high blood sugar Albuterol Significant Adverse Reactions Cardiac CNS Paradoxical Bronchospasm •arrhythmias •cardiomyopathy •anxiety, nervousness •hyperactive behavior •possibly hypersensitivity reaction Albuterol Warnings/Precautions • Cardiovascular disease – per AHA albuterol can either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction • Diabetes – can increase blood sugar • Glaucoma – can increase IOP • Hypokalemia – can decrease hypokalemia further • Hyperthyroid – can stimulate thyroid activity • Seizures – can stimulate CNS • Do not exceed recommended dose Albuterol – Drug Interactions • Beta blockers (beta 1 selective) – may decrease bronchodilation effects • Beta blockers (nonselective) – may significantly reduce bronchodilation effects – AVOID USE • Loop/Thiazide diuretics – increased hypokalemia • QTc prolonging agents – may enhance QTc prolongation Albuterol • Pregnancy – preferred short acting beta-2 agonist for management of asthma during pregnancy • Breastfeeding – unknown if albuterol is present in breast milk, per manufacturer consider risks of infant exposure, benefits of breastfeeding to the infant, benefits of treatment to mother; compatible with breastfeeding per WHO Albuterol Monitoring • • • • • • Pulmonary function tests BP, Heart rate, ECG periodically CNS stimulation Blood work – K+, blood sugar, Cr Asthma symptoms Frequency of albuterol use (escalate long term anti-inflammatory maintenance treatment in patients using SABA more than 2 days/week Long- Acting Beta Agonists LABA • Long duration of action, bronchodilation for at least 12 hours • Monotherapy with LABA contraindicated • LABA useful adjunctive therapy for attaining control in moderate to severe asthma LABA Agents Salmeterol (Serevent) Formoterol (Foradil) Formoterol • Indications oMaintenance treatment of bronchoconstriction in patients with COPD oUsed in combination therapy with corticosteroids oNOT FOR USE AS MONOTHERAPY Formoterol • Mechanism of Action oRelaxes bronchial smooth muscle by action on beta-2 receptors with little effect on heart rate Formoterol • Dosage Forms oNebulizer solution 20 mcg/2mL oCombination products - Budesonide/Formoterol (Symbicort), Formoterol/Mometasone (Dulera) Formoterol Dosing • Adult • Pediatric – not labeled for use in pediatrics • Renal impairment – no dose adjustments • Hepatic impairment – no dose adjustments Formoterol • Pharmacokinetic/Pharmacodynamic Factors oOnset of action – significant bronchodilation within 5 minutes oDuration – improvement for 12 hours oHalf life – DPI 10-14 hours; nebulizer 7 hours oAvailable as nebulizer solution Formoterol - Warnings • Asthma related deaths – monotherapy with LABA is contraindicated, has been associated with severe exacerbations and death • Paradoxical bronchospasm • Hypersensitivity – urticaria, angioedema, rash • Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics. Formoterol • Adverse effects – comparable with SABA • Disease related concerns – comparable with SABA • Drug interactions – comparable with SABA • Monitoring – comparable with SABA Formoterol • Pregnancy – may be used when LABA needed for management of asthma in pregnancy • Breastfeeding – according to manufacturer, decision to continue or discontinue should consider risk of infant exposure, benefits of breastfeeding to infant, benefits of treatment to mother