A premature newborn baby of 29 weeks gestational age developed five episodes of apnea on the second day of life. The apnea episodes lasted for 20 to 30 seconds and required administration of oxygen. Three prolonged episodes required bag and mask ventilation. He was given an intravenous drug to manage apnea. Which of the following drugs was most likely administered to him?
A. Epinephrine B. Albuterol C. Theophylline D. Atropine E. Zafirlukast
Theophylline -theophylline (elixophyllin®; theo-24®) aminophylline chemistry o related to the compound caffeine o theophylline: 1,3-dimethylxanthine o aminophylline: theophylline-ethylenediamine complex salt form that has increased solubility at neutral ph pharmacokinetics o oral and parenteral administration o rapidly and completely absorbed oral bioavailability ~100% absorption may be delayed at night related to patient being in a supine position o drug possesses a very narrow therapeutic window requires scheduled monitoring of plasma levels o large variation in drug clearance between patients due to differences in hepatic metabolism (requires individualization of dosage and plasma concentration monitoring) increased clearance is seen in children (1-16 years old), cigarette/marijuana smokers, and patients concurrently taking phenytoin, phenobarbital, and rifampin decreased clearance is seen in patients with liver disease, pneumonia, and heart failure (doses should be cut in half and plasma levels monitored closely); co-administration with erythromycin, quinolone antibiotics, allopurinol, cimetidine, fluvoxamine, zileuton, zafirlukast; viral infections and vaccination pharmacodynamics o mechanism of action remains unclear several mechanisms have been proposed nonselective inhibition of phosphodiesterases (pde) adenosine receptor antagonist adenosine induces bronchoconstriction in asthmatic patients by stimulating release of histamine and lts stimulation of release of interleukin-10 (il-10) o il-10 possesses a broad spectrum of anti-inflammatory effects inhibition of the pro-inflammatory transcription factor nf-b induction of apoptosis in eosinophils and neutrophils activation of histone deacetylases (hdac) o hdacs partially mediate corticosteroid-mediated suppression of pro-inflammatory genes increase circulating catecholamines inhibition of ca2+ influx into inflammatory cells inhibition of pg-mediated effects antagonism of tnf- o pharmacological actions/effects induces bronchodilation exerts anti-inflammatory action inhibits the late response to inhaled allergen reduces infiltration of eosinophils and cd4+ lymphocytes into airways after allergen challenge reduces the total number and production of neutrophils in induced sputum, [il-8], and neutrophil chemotactic responses induces mild cortical arousal with increased alertness and deferral of fatigue (low-to-moderate doses); nervousness and tremor (large doses); medullary stimulation, convulsions, possible death (very high doses) positive chronotropic and inotropic effects on the heart stimulates secretion of both gastric acid and digestive enzymes exerts weak diuretic action improves contractility and reverses fatigue of the diaphragm (especially in copd patients) clinical pharmacology o clinical uses therapy of acute and chronic asthma in cases of acute asthma, these drugs relieve airflow obstruction o rarely given, unless poor response to other therapies exist in cases of chronic asthma, these drugs reduce the severity of symptoms and time lost from work/school o particularly useful for the relief of nocturnal symptoms improves long-term control of asthma when taken as the sole maintenance treatment or when added to ics removal of these drugs usually causes worsening of the disease bronchodilator therapy in copd usually added to other copd drug regimens instead of being used alone removal of these drugs usually causes worsening of the disease control of apnea of preterm infants attributed to the immaturity of medullary respiratory center control of cheyne-stokes respiration due to a decreased sensitivity of respiratory center to co2 o adverse effects/toxicity serious reactions seizures, arrhythmias, hypotension, shock, exfoliative dermatitis common reactions nausea/vomiting, headache, insomnia, diarrhea, irritability, restlessness, tremor, transient diuresis o contraindications pregnancy/lactationcategory c/precaution (probably safe)