NR566 Chapter 17 Complete Study Guide - All concepts and terms

CHAPTER 17: DRUGS AFFECTING THE RESPIRATORY SYSTEM SHORT-ACTING BETA AGONISTS  Albuterol (Ventolin), metaproterenol (Alupent), terbutaline (Brethine), bitolterol (Tornalate), pirbuterol (Maxair), levalbuterol (Xopenex) LONG-ACTING BETA AGONISTS  Arformoterol (Brovana), salmeterol (Serevent), formoterol (Foradil), indacaterol (Arcapta Neohaler)  Associated risk for intubation and death.  Should not be used alone- used in combination with an asthma controller medication such as inhaled corticosteroid (for peds/adolescents, single preparation both LABA and corticosteroid- to enhance compliance)- see BLACK BOX WARNING  Should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medication. Pharmacodynamics  act on the smooth muscle of the bronchial tree to reverse bronchospasm, thereby decreasing airway resistance and residual volume and increasing vital capacity and airflow.  Beta agonists stimulate beta-2 adrenergic receptors in the lungs to increase production of cyclic adenosine monophosphate (cAMP) by activation of adenyl cyclase, the enzyme that catalyzes the conversion of ATP to cAMP.  Increased cAMP concentrations relax bronchial smooth muscle and inhibit release of mediators of immediate hypersensitivity from cells, especially from the mast cells.  ALBUTEROL- selective beta-2 agonist with minor beta-1 activity. o a.k.a. “Salbutamol” o can increased HR by stimulating beta-2 receptors in the heart, and beta-2 receptors in vascular smooth muscles (vasodilation -> decreased DBP -> increased HR) o has fewer cardiac and CNS effects than other o drug of choice of FIRST LINE THERAPY o similar structure: levalbuterol, pirbuterol  TERBUTALINE- selective beta-2 agonist with minor beta-1 activity (similar to albuterol) o Also known to inhibit uterine contractions o To prevent contractions related to preterm labor (off label use).  SALMETAROL and FORMOTEROL- exert long-lasting bronchoprotection effects against allergen-, exercise-, histamine-, and methacholine-cause bronchospasm. Pharmacotherapeutics  CONTRAINDICATIONS: o cardiac arrhythmias associated with tachycardia or heart block caused by digitalis intoxication, angina, narrow-angle glaucoma, organic brain damage, shock during general anesthesia o pheochromocytoma (diagnosed or suspected)- may cause severe HTN  MONITOR CLOSELY FOR ADVERSE EFFECTS (cardiovascular system): patients with HTN, ischemic heart disease, coronary insufficiency, CHF, hx of stroke and/or cardiac arrhythmias  BLACK BOX WARNING: salmeterol and formoterol o Respiratory-related asthma and asthma-related deaths and risk is higher for African Americans.  Patients on digoxin: monitor closely with use of albuterol- increased volume of distribution of digoxin and can cause up to a 30% decrease in blood digoxin levels.  All are PREGNANCY CATEGORY C, except -> Terbutaline (pregnancy category B) Clinical use  Bronchospasm- asthma, bronchitis, COPD  Exercise-induced bronchospasm Drug interactions  Digitalis glycosides- caution and careful monitoring of patient’s EKG (increased risk of cardiac arrhythmia)  Beta-adrenergic blockers- mutual inhibition of therapeutic effects  TCA and MAOI- may potentiate effects on vascular system when taken with albuterol, metaproterenol, or terbutaline.  Beta agonists- coadministration may lead to hypokalemia or EKG changes. Adverse drug reactions  Drug-induced hyperglycemia for pts with DM- insulin may need to be increased.  Overuse may lead to: seizures, hypokalemia, anginal pain, HTN  Increased HR  Tremors  GI upset- take with food for oral forms  Tachycardia, chest pain, muscle tremors, dizziness, flushing- inform healthcare provider. XANTHINE DERIVATIVES  Methylxanthines- have declined in importance in the treatment of asthma o Caffeine o Aminophylline Pharmacodynamics  Work directly by unknown mechanism believed to be mediated by selective inhibition of specific phosphodiesterases (PDEs) -> increase in cAMP -> bronchial smooth muscle and pulmonary vessel relaxation  Theophylline and Caffeine o powerful CNS stimulants o increase gastric acid secretion – may cause n/v o stimulate skeletal muscles- tremors o increased renal blood flow -> increased GFR -> increased Urine output (diuresis)  Theophylline o has a greater effect on cardiovascular system o directly stimulates the myocardium -> increased myocardial contractility -> increased HR o relaxes vascular smooth muscles -> dilates coronary, pulmonary, and systemic blood vessels o increased Na and Cl excretion on the renal tubules Pharmacotherapeutics  CONRAINDICATIONS: o Theophylline:  Hypersensitivity to xanthene  PUD  Underlying seizure d/o  For nursing mothers, babies can have: • Transient tachycardia • Irritability • Vomiting o Caffeine  Hypersensitivity to caffeine  Use of caffeine sodium benzoate formulation in neonates  MONITOR CLOSELY: Theophylline: patients with HTN, ischemic heart disease, coronary insufficiency, CHF, hx of stroke, and cardiac arrythmias; use in children  Theophylline is PREGNANCY CATEGORY C. Clinical use  Theophylline o Reserved for long-term management of asthma o “Alternative, not preferred” therapy in step 2 of asthma care (after trial of LABA in combination with inhaled steroids) o COPD- not recommended as first line, BUT, if pt is stable on theophylline -> no reason to d/c the drug.  Caffeine o Apnea of prematurity- loading dose of caffeine citrate 10-20mg/kg and maintenance dose of 5mg/kg Drug interactions  Tobacco- increased theophylline clearance (monitor theophylline levels when a patient started or quit smoking)  CYP1A2, CYP2E1, CYP3A3/4 substrate of the CYP450 isoenzyme – increased/decreased theophylline clearance, also metabolized caffeine. o Cimetidine, ketoconazole, fluconazole, mexiletine, phenylpropanolamine (may impair caffeine metabolism -> increased serum levels)  Benzodiazepines- sedative effects may be antagonized by theophylline  Other beta-2 agonist bronchodilators- toxicity  Lithium levels- decreased with theophylline  High CHO and CHON increases elimination of theophylline.  Charcoal-broiled foods- accelerates the hepatic metabolism of theophylline Adverse drug reactions  Theophylline o (uncommon if serum levels is <20mcg/mL) usually common among patients on initiation therapy (15-20mcg/mL)  CNS: Irritability, Restlessness, Seizures, Insomnia  GI: Gastroesophageal reflux  CV: Palpitations, Tachycardia, Hypotension, Life-threatening arrhythmias  OTHERS: Rash, diuresis, tachypnea o 20mcg/mL: n/v/d, headache, insomnia, irritability o >35mcg/mL: hyperglycemia, hypotension, cardiac arrhythmias, tachycardia, seizures, brain damage, death o SIGNS OF TOXICITY:  N/V  Insomnia  Jitteriness  Headache  Rash  Severe GI pain  Restlessness  Convulsions  Irregular heartbeat