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It was subsequently found that individuals metabolize theophylline at differing rates, which makes it difficult to determine
therapeutic doses
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is 100% theophylline
anhydrous theophylline
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Dyphylline is not a theophylline but a?
derivative (also 1/10 as potent)
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Because individuals vary in the rate at which theophylline is metabolized, dosage must be titrated to clinical
effectiveness
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Theophylline effectiveness to a therapeutic serum level is what for COPD and what for asthma management?
5-10ug/mL and 5-15 ug/mL
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GOLD recommendations for the use of theophylline in COPD suggest a target serum level of
5-15 ug/mL
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Because of the variability in the rate at which individuals metabolize theophylline and the other factors that affect theophylline metabolism and clearance rates, dosage schedules are used to titrate the drug. These schedules are found in the product literature, references such as
Drug Facts and Comparisons and Physicians� Desk Reference, and general pharmacology texts.
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Dosage of theophylline can be guided by the clinical reaction of the patient or, better, by measurement of
serum levels
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Complete tables for different ages and clinical applications should be consulted when administering
theophylline
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Theophylline has a narrow therapeutic margin, and side effects such as gastric upset, headache, insomnia, nervousness, palpitations, and diuresis occur frequently, even within the
therapeutic range of dosing
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An important problem with the use of theophylline is its narrow therapeutic margin; there is very little difference between the dose and serum level that give therapeutic benefit and that cause
toxic side effects
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Reactions to levels of theophylline also can be unpredictable from
patient to patient
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can cause elevated serum levels of theophylline for a given dose because of decreased liver metabolism of the drug
viral hepatitis or left ventricular failure
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An opposite effect�decreased serum levels�is caused by cigarette smoking, which stimulates the production of liver enzymes that inactivate
methylxanthines
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� agonists and theophylline have an additive effect and are often combined when treating patients with
asthma or COPD
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Theophylline may antagonize the sedative effect of benzodiazepines (e.g., Valium). Theophylline can also reverse the paralyzing effect of nondepolarizing neuromuscular blocking agents (pancuronium and atracurium) in a dose-dependent manner. This is important to realize when
paralyzing patients with severe asthma to facilitate ventilatory support and when intravenous administration of aminophylline is used.
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Theophylline has been relegated to the level of a second-line or third-line drug in treating
asthma
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Theophylline is considered only if � agonists and antiinflammatory therapy fail to
control symptoms
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In COPD, the nonbronchodilating effects of theophylline, such as ventilatory drive stimulation, and enhanced respiratory muscle function are of value, although use of theophylline in COPD is
debated
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Theophylline and its salt, aminophylline, are listed as bronchoactive agents for managing an acute exacerbation of COPD in the GOLD guidelines; however, use of other
bronchodilators is preferred
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COPD guidelines suggest the use of inhaled � agonists (e.g., albuterol) and anticholinergics (e.g., ipratropium) over the use of theophylline because of its
side effects
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Although theophylline is classified as a bronchodilator, it has a relatively weak
bronchodilating action
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The efficacy of theophylline in obstructive lung disease may be due to its nonbronchodilating effects on
ventilation
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Substance that reduces adhesion.
Abhesive
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Rheologic property characteristic of solids; it is represented by the storage modulus G'.
Elasticity
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Medication meant to increase the volume or hydration of airway secretions.
Expectorant
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Macromolecular description of pseudoplastic material having both viscosity and elasticity.
Gel
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Protein with attached oligosaccharide units.
Glycoprotein
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The principal constituent of mucus and a high-molecular-weight glycoprotein, it gives mucus its physical/chemical properties such as viscoelasticity.
Mucin
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Term connoting any medication or drug that has an effect on mucus secretion; may include mucolytic, expectorant, mucospissic, mucoregulatory, or mucokinetic agents.
Mucoactive agent
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Medication that increases cough or ciliary clearance of respiratory secretions.
Mucokinetic agent
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Medication that degrades polymers in secretions. Classic mucolytics have free thiol groups to degrade mucin, and peptide mucolytics break pathologic filaments of neutrophil-derived DNA or actin in sputum.
Mucolytic agent
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Drug that reduces the volume of airway mucus secretion and appears to be especially effective in hypersecretory states, such as bronchorrhea, diffuse panbronchiolitis (DPB), CF, and some forms of asthma.
Mucoregulatory agent
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Medication that increases viscosity of secretions and may be effective in the therapy of bronchorrhea.
Mucospissic agent
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Secretion, from surface goblet cells and submucosal glands, composed of water, proteins, and glycosylated mucins. The glycoprotein portion of the secretion is termed mucin. Mucus (noun) is the secretion; mucous (adjective) is the cell or gland type.
Mucus
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Sugar that is the individual carbohydrate unit of glycoproteins.
Oligosaccharide
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Purulent material in the airways. From the Greek word for inflammation. When expectorated, phlegm is called sputum.
Phlegm
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Study of the deformation and flow of matter.
Rheology
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Macromolecular description of the respiratory secretion in true solution, with the physical property of viscosity (usually referred to as the periciliary layer).
Sol
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Expectorated phlegm that contains respiratory tract, oropharyngeal, and nasopharyngeal secretions and bacteria and products of inflammation including polymeric DNA and actin.
Sputum
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Resistance of liquid to sheer forces. A rheologic property characteristic of liquids and represented by the loss modulus G'.
Viscosity
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Mucoactive therapy should be considered after therapy to decrease
infection and inflammation
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is a major defense mechanism of the lung. Failure of this system results in mechanical obstruction of the airway, often with thickened, adhesive secretions.
The self-renewing, self-cleansing mucociliary escalator
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is found in several areas of the body, including the airways, gastrointestinal tract, and genital tract.
Mucus
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Historically in respiratory care, drug therapy for secretions has been aimed at liquefying thick mucus to a watery state called
Mucolysis
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lubricates, waterproofs, and it protects against osmotic or inflammatory changes. It can entrap microorganisms, inhibiting chronic bacterial infection and biofilm formation.
Mucus barriers
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The general indication for mucoactive therapy is to
reduce the accumulation of airway secretions, with concomitant improvement in pulmonary function and gas exchange and the prevention of repeated infection and airway damage
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Diseases in which mucoactive therapy is indicated are those with hypersecretion or poor clearance of airway secretions, including
Cystic fibrosis (CF), acute bronchitis and chronic bronchitis (CB), pneumonia, diffuse panbronchiolitis (DPB), primary ciliary dyskinesia, asthma, and bronchiectasis
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The use of mucoactive therapy to promote secretion clearance should be considered after therapy to decrease infection and inflammation and after minimizing or removing irritants to the airway, including
Tobacco smoke
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The source and properties of airway secretions and the mechanisms of action for the mucoactive agents are the basis for
clinical use of this class of drugs.
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The secretion lining the surface of the airway is called mucus and has been described as having two phases:
(1) A gel layer (0.5 to 20 �m) is propelled toward the larynx by the cilia and floats on top of (2) a watery periciliary layer (7 �m, the height of a fully extended cilium)
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Although there are many cell types in the mammalian airway, the essential secretory structures of the mucociliary system are the following:
Surface epithelial cells, Pseudostratified columnar ciliated epithelial cells, Surface goblet (or surface mucous) cells, Clara cells in the distal airway, Submucosal glands, with serous and mucous cells
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The surface of the trachea and bronchi includes primarily ciliated cells and goblet cells, at a ratio of approximately
5:1
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There are more than _______ goblet cells per square millimeter of normal airway mucosa
6000
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Submucosal glands below the epithelial surface are thought to provide much of the airway surface
mucin
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two types of cells that are found in the glands?
mucous and serous
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Secretions from the serous and mucous cells mix in the submucosal gland and are transported through a ciliated duct onto the
airway lumen
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The airway secretion consists of a mucous layer, where mucin glycoprotein is located, and a
watery, periciliary layer
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Mucociliary transport results from the movement of the mucus gel by
the beating cilia
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A ciliary beat is composed of two kinds of strokes:
effective (power) stroke and recovery stroke
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the cilium moves in an upright position through a full forward arc, to contact the underside of the mucus layer and propel it forward.
effective stroke
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the cilium swings back around to the starting point near the cell surface, to avoid pulling secretions back
recovery stroke
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lies at the tips of the cilia and separates the periciliary fluid from the mucus gel. This layer allows the cilia to transmit kinetic energy effectively to the mucus without becoming entangled. This layer also facilitates mucus spreading as a continuous layer and prevents water loss from the periciliary fluid.
functional surfactant layer
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Mucociliary transport velocity varies in the normal lung and has been estimated at about 1.5 mm/min in peripheral airways and 20 mm/min in
the trachea
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Mucociliary transport are slower in the presence of the following conditions or substances, many of which are associated with airway damage:
COPD, CF, narcodics, ET suctioning, airway trauma, trach., smoking, pollutants, hyperoxia, and hypoxia
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no association between milk and dairy product intake and upper or lower respiratory tract symptoms of
congestion or nasal secretion weight
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A healthy person is thought to produce about _____ of mucus per 24 hours
100mL
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is affected by many drugs, including surfactants and beta agonist agents.
Mucociliary clearance
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forms a protective barrier between the respiratory tract epithelium and the environment.
airway mucus
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