Compounds Commonly Administered To The Lung

Chapters 2 and 4 thoroughly reviewed the compounds administered to the lung and their chemical origins and activity. Most compounds administered to the lung are bronchodilators 68 -76 . These fall in the general categories of catecholamines 74,77 , resorcinols 74,78-80 , saligenins 74,81 , and prodrugs 74,82,83 , all of which exhibit or result in P-adrenergic receptor agonist activity. Other common agents are anticholinergic and corticosteroid agents 44,84-88 and cromolyn sodium 89-91 , which...

Increasing Duration Of Therapeutic Action The Case For Nanoparticles

Various attempts to achieve sustained drug action in the lungs following drug deposition via aerosol have led to promising results in animals but so far disappointing results in humans. These include the use of liposomes 19 , polymers 20 , and surfactants 21 and the modulation of particle size through the lowering of particle density 22 . Among the factors working against long action of drugs in the lungs are natural clearance mechanisms related to airway mucocilia and macrophages that remove...

Liquid Drain

Figure 7 Schematic diagram of the Babington nebulizer. flowing over the spherical surface. Excess liquid is collected and recirculated. Smaller quantities of liquid are required for use in the Babington than ultrasonic devices due to the need for more material to saturate the atmosphere at the elevated ambient temperatures in the latter nebulizer. Jet nebulizers, in general, require a higher operating pressure than the Babington system to produce therapeutic aerosols. Of note, however, is that...

Bronchodilators

Associated with airways extending from the trachea to the terminal bronchioles is a layer of smooth muscle. In the trachea, smooth muscle constitutes a fraction of the circumference and connects the ends of incomplete cartilage rings. The fractional contribution of smooth muscle increases in lower airway segments such that the bronchi and bronchioles are encircled by a layer of smooth muscle. The length of the smooth muscle cells at any particular time determines the circumferential length of...

Cascade Impactors

Cascade impaction is one of the oldest methods for the dynamic characterization of aerosol particles. The method is used daily for the characterization of pharmaceutical aerosols, despite not currently being a pharmacopoeial requirement. The Food and Drug Administration first recognized the popularity of this type of sizing device by setting a standard for its use in the assessment of generic pharmaceutical aerosols for bioequivalence 40 . This has been superceded by pharmacopoeial and...

References

Aerosols for therapy and diagnosis. Eur J Nucl Med 1993 20(12) 1201-1213. 2. Newman SP, Pitcairn GR, Hirst PH. A brief history of gamma scintigraphy. J Aerosol Med 2001 14(2) 139-145. 3. Gonda I. Scintigraphic techniques for measuring in vivo deposition. J Aerosol Med 1996 9(suppl 1) S59-S67. 4. Newman SP. Scintigraphic assessment of therapeutic aerosols. Crit Rev Ther Drug Carrier Syst 1993 10(1) 65-109. 5. Kunka R, Andrews S, Pimazzoni M, Callejas S, Ziviani L,...

Mucolytic Agents

Mucolytic agents such as N-acetylcysteine (NAC) have been used by aerosol delivery in an attempt to aid in sputum clearance. Supplied in sufficient quantity, acetylcysteine will help liquefy tenacious secretions and make their clearance easier. A review of studies on the use of NAC in CF concluded the evidence does not support its use, either via nebulizer or by mouth 93 . Intravenous NAC was tested and found not useful in acute respiratory distress syndrome 94 . In one study,...

Adverse Reactions And Effects Of Aerosolized Pentamidine

Inadequate experience has been obtained to determine the incidence of the infrequent adverse reactions that will be associated with aerosolized pentamidine therapy for acute PCP. In case reports, bronchial bleeding has been reported with high-dose therapy in one center 43 . This was associated with an invasive procedure and has not been seen in the large prospective treatment trial. Case reports of hypoglycemia, rash, and conjunctivitis have also been reported 44,45 . The conjunctivitis is not...

Glucocorticoids GC

Current effective therapies for asthma have focused on treating the symptoms of the disease. Asthma is characterized by inflammation of the lung thus, the most prescribed agents to date are the glucocorticoids (GC), due to their widespread anti-inflammatory properties 70-72 . The glucocorticoid drugs budesonide (25), beclomethasone dipropionate (26), and triamcinolone (27) have long been employed for use in treating asthma. Fluticasone propionale (28) is a more recent addition, and mometasone...

Drugmonoclonal Antibody Conjugates For Targeting To The Lung

Another drug-carrier system that has been investigated as a means of achieving specific tissue targeting is the use of an antibody directed against the tissue that is the proposed site of action of the drug. Although this approach is not new, because pioneering work in this area was carried out as early as 1958 202 . Recently, it has become evident that monoclonal antibody (mAb) biotechnology is effective in a wide range of disease. The current estimated market for these agents is about 25...

Measures of Pulmonary Volumes

Spirometry is the measurement of the volume of air moving into or out of the airways. In this process, various ventilatory maneuvers are undertaken that Figure 6 Spirometric representation of lung volumes. Figure 6 Spirometric representation of lung volumes. permit an estimation of pulmonary volumes and capacities (Fig. 6). Such measurements are valuable for diagnosis of airway disease because pathological conditions can modify specific pulmonary volumes. Definitions of the specific lung...

Introduction

The measurement of lung deposition of inhaled therapeutics and its interpretation has been debated within the field of inhaled drug delivery science for many years. Historically, two-dimensional gamma scintigraphy (planar imaging) has been used to demonstrate total and regional lung deposition of drugs inhaled from selected aerosol delivery systems 1-4 . Efforts have been made to link total lung deposition with the clinical parameters of efficacy and safety, though with limited success....

Bioadhesives And Drug Targeting To The Lung

The use of bioadhesive targeting as a means for specific delivery of drugs has gained some impetus since the late 1980s 180 . The term bioadhesion refers to interactions involving multiple molecular and usually noncovalent bonds. However, a bioadhesive agent, to be effective as a drug carrier, must initially be trapped or sequestered by endothelial or epithelial cells, followed by multiligand binding of the surface material of the carrier particle to cell surface determinants, which then...

Xanthine Derivatives and Phosphodiesterase Inhibitors

Xanthine derivatives, which include theophylline and its salt, aminophylline, are very effective in treating obstructive airways disease. However, the means by which these agents induce airway smooth muscle relaxation remains unclear. The primary mechanisms proposed include (1) inhibition of phosphodiesterase, the enzyme responsible for metabolism of the intracellular messenger, cyclic adenosine 3',5'-monophosphate (cAMP) 39 and (2) antagonism of receptors for adenosine, an agent that is...

Increasing Bioavailability The Case For Ethanol

The commercial need to improve relative bioavailability for systemic-targeted inhalation therapies relates to both basic economics and safety. Increased bioavailabilities obviously translate into smaller masses of drug product per therapeutic dose and potentially lesser negative side effects. Given the relatively high delivery efficiencies achievable with the best inhaler systems, one path toward achieving higher bioavailabilities is the use of the chemical enhancers 14 . The goal of the...

Prodrug Approaches To Extending Drug Activity In The Lung

Most of the research centered on the targeting of drugs by the prodrug approach has been carried out on b2 stimulants structurally related to isoproterenol and similar drugs. The basic approach has been to esterify the catechol functions of isoproterenot to achieve better uptake in lung tissues of the resulting inactive lipophilic drug, which may then be metabolically cleaved by lung esterases to release the active parent compound 124,125 . In addition, esterification of the catechol function...

Advances in MDI and DPI Technology and

Enantiomer Preparations of Inhaled Drugs. There has been much interest in the differences in effects of enantiomers of many medications, and beta agonist adrenergic bronchodilators have received much attention. Evidence suggests that the (R)-enantiomer of albuterol is mainly responsible for bronchodilation while the (S)-enantiomer may stimulate airway reactivity. Data suggest, however, that after aerosol delivery, the systemic absorption for (R)-albuterol is faster than for (S)-albuterol and...

Methods for Assessing Pulmonary Targeting

Inhalation therapy has been introduced into the clinics to ensure pulmonary effects with reduced systemic side effects. Animal and human studies for assessing pulmonary targeting are summarized next. Table 4 summarizes approaches for assessing pulmonary targeting. Assessment of Pulmonary Targeting in Animal Models. Animal models are important tools in assessing the pharmacodynamic performance of antiasthma drugs. Pulmonary models have been developed for rat and mice, which allow the assessment...

Powder Inhalers

Dry Powder Inhaler Devices Pictures

Today there are essentially two types of DPIs, those that use drug filled into discrete individual doses, e.g., either a gelatin capsule or a foil-foil blister, and those that use a reservoir of drug that meters out doses when required. Both are now widely available around the globe and are gaining broad acceptance. There is clearly considerable interest in these devices because they do not require CFC propellants to disperse the drug and, as such, can be regarded as ozone-friendly delivery...

Muscarinic Cholinoceptor Antagonists

Airway smooth muscle cells are innervated (receive nerve supply) by cholinergic nerves. Increased cholinergic nerve activity is associated with irritant stimulation postganglionic cholinergic nerves to result in the release of acetylcholine from postganglionic nerve terminals, thus of sensory nerves in the airways that send impulses to the central nervous system and result in an increase in cholinergic nerve activity to the airways. Electrical impulses (action potentials) emanating from the...