Xanthines: Uses, Side Effects, and Clinical Indications (PDF)

Chapter 8 Xanthines Copyright © 2016, Elsevier Inc. All rights reserved.  Use of Xanthines Effects of xanthines Xanthines induce cerebral vasoconstriction; They stimulate cardiac muscle stimulat...

Chapter 8 Xanthines Copyright © 2016, Elsevier Inc. All rights reserved.  Use of Xanthines Effects of xanthines Xanthines induce cerebral vasoconstriction; They stimulate cardiac muscle stimulation, smooth muscle relaxation; and CNS stimulation Mechanism of action xanthines Although Xanthines have a bronchodilating effects, stimulate ventilatory drive, and strengthen the diaphragm, their exact mechanism of action is unclear. Used to treat: COPD Apnea of prematurity Asthma Copyright © 2016, Elsevier Inc. All rights reserved. 2  Clinical Indications for the Use of Xanthines: Asthma Use in asthma Theophylline: maintenance therapy (step 2 or alternative in step 3 with ICS of mild, persistent asthma Patients older than 5 years of age Side effects and narrow therapeutic index may make it a poor choice vs. other agents Copyright © 2016, Elsevier Inc. All rights reserved. 3  Clinical Indications for the Use of Xanthines: COPD Use in COPD Theophylline: recommended by GOLD as alternative to β2-agonist and anticholinergics Not used in acute exacerbations Copyright © 2016, Elsevier Inc. All rights reserved. 4  Clinical Indications for the Use of Xanthines: AOP Use in apnea of prematurity First-line treatment Theophylline most extensively used in the past, but caffeine citrate may be a better choice (safer, higher therapeutic index) Copyright © 2016, Elsevier Inc. All rights reserved. 5  Specific Xanthine Agents Also known as methylxanthines Found as alkaloids in plant species Theophylline Tea leaves Theobromine Cocoa seeds or beans Caffeine Coffee beans and kola nuts Cocoa seeds or beans Tea leaves Copyright © 2016, Elsevier Inc. All rights reserved. 6  Titrating Theophylline Doses Individuals metabolize theophylline at different rates Difficult to determine therapeutic doses Equivalent doses of theophylline salts Anhydrous theophylline = 100% theophylline Salts of theophylline not pure by weight Copyright © 2016, Elsevier Inc. All rights reserved. 7  Titrating Theophylline Doses (Cont.) Serum levels of theophylline 20 μg/mL: Nausea >30 μg/mL: Cardiac arrhythmias 40 to 45 μg/mL: Seizures Asthma 5 to 15 μg/mL COPD 5 to 10 μg/mL 8 Copyright © 2016, Elsevier Inc. All rights reserved. Titrating Theophylline Doses (Cont.) Methods of titration Clinical reaction of patient Serum drug levels 1–2 hours after administration (immediate release) 5–9 hours after administration (sustained release) Theophylline dosage may be guided by clinical reaction of the patient, but to avoid toxic side effects, it is best to measure serum blood levels at the time of peak absorption (1-2 hours after administration) of immediate release forms and (5-9 hours after the morning dose of sustained –release forms) Copyright © 2016, Elsevier Inc. All rights reserved. 9  Theophylline Toxicity and Side Effects Narrow therapeutic margin Distressing side effects may occur at therapeutic levels Inhaled theophylline is being studied Common side effects: Gastric upset Not recommended in patients with peptic ulcer or acute gastritis Headache Anxiety Nervousness Diuresis Copyright © 2016, Elsevier Inc. All rights reserved. 10  Factors Affecting Theophylline Activity Conditions affecting liver/kidneys Interactions with other drugs (see Box 8-2 in the textbook for full list) Conditions that increase theophylline levels: Viral hepatitis Left ventricular failure Condition that decreases theophylline levels: Smoking Additive effect: β-Agonists Copyright © 2016, Elsevier Inc. All rights reserved. 11  Clinical Uses Asthma Use debated Only after other relievers and controllers have failed COPD If ipratropium bromide and β2-agonist fail to provide control Copyright © 2016, Elsevier Inc. All rights reserved. 12  Nonbronchodilating Effects of Theophylline Increase in force of respiratory muscle contractility Increase in respiratory muscle endurance Increase in ventilatory drive Cardiovascular effects Increased cardiac output Decreased pulmonary vascular resistance Anti-inflammatory effects Copyright © 2016, Elsevier Inc. All rights reserved. 13  Use in Apnea of Prematurity Xanthines are the first-line choice when nonpharmacological methods are unsuccessful Caffeine citrate is preferred over theophylline Loading dose of caffeine citrate is 20 mg/kg Daily maintenance dose of 5 mg/kg Copyright © 2016, Elsevier Inc. All rights reserved. 14 Respiratory Care Assessment of Xanthines – Long Term Monitor pulmonary function studies Education regarding peak flow meters to assess the severity of an episode of asthma Education to emphasize that xanthines do not treat underlying inflammation or prevent progression of asthma or COPD Assess serum blood levels of the agent Copyright © 2016, Elsevier Inc. All rights reserved. 15