Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 4

1.2.1.2 Corticosteroids
Figure 1.1b shows the structure of a glucocorticosteroid molecule. Inhaled corticosteroids (ICS)
were introduced to treat the underlying cause of asthma, inlammation, and are rapidly becoming
the preferred treatment for asthma. 18 Corticosteroids had been used as an oral therapy for severe,
life-threatening conditions in the form of prednisone and prednisolone. The development of agents
with some lung speciicity gave rise to the concept of inhaled steroid therapy. The irst agent to be
developed was beclomethasone (GSK, RTP, NC and Schering Plough, White Plains, NJ), followed
closely by triamcinolone (Aventis, Collegeville, PA); both were used in pressurized MDIs. In the
late 1980s and early 1990s, two steroids with a high degree of lung speciicity, budesonide and luti-
casone, were developed as DPI products. These molecules were shown to induce lower side effects,
notably cortisol suppression, than their predecessors. Recently, more drugs have arrived on the mar-
ket such as mometasone furoate (MF) as a DPI (Asmanex Twisthaler, Schering Corp., Kenilworth,
NJ) 19 and ciclesonide as a pressurized MDI (Alvesco, Nycomed GmbH, Zurich, Switzerland). 20
MF may also be prescribed for COPD. 21
1.2.1.3 Anticholinergics
Figure 1.1c shows the structure of an anticholinergic agent. Anticholinergic agents are known para-
sympathetic antagonists that operate on the opposing arm, balancing bronchomotor tone to the
sympathomimetic agents described in Section 1.2.1.1. The irst anticholergic agent was ipratropium,
which was followed by oxitropium. Cholinergic receptors are known to be centrally located in the
airways and, consequently, these agents are effective in dilating the bronchioles in this region.
Tiotropium is a recent addition to this category of drugs, which has been shown to be very effective
in COPD, which requires not only bronchodilatation but also the loosening of mucus. All of these
agents are produced by Boehringer Ingelheim (Ingelheim, Germany).
1.2.1.4 Anti-Inlammatory Agents
Figure 1.1d shows the structure of a unique anti-inlammatory agent. Disodium cromoglycate
(cromolyn sodium) (Aventis, Collegeville, PA) was developed in the 1960s and 1970s and has
been shown to have a number of effects in the lungs. The most prominent effect is mast cell
stabilization and the prevention of release of inlammatory mediators. However, it is not clear
what the dominant action is that renders this molecule therapeutically effective. This molecule
has the distinction of being the irst in modern times to be administered as a dry powder aerosol.
A follow-up molecule was developed by the same company in the 1980s, nedocromil sodium.
Contained in a pressurized MDI (Tilade, King Pharmaceuticals, Cary, NC), it was a treatment
for asthma until the FDA ban on CFCs in inhalers took effect in 2008 and U.S. production was
terminated. 22
1.2.1.5 Antimicrobials
A number of antimicrobial agents have been delivered to the lungs to treat different diseases.
Pentamidine (Fujisawa, North Chicago, IL and Aventis, Collegeville, PA) was delivered for the
treatment of Pneumocystis carinii pneumonia (PCP). This organism was originally considered to
be a parasite but has recently been redesignated taxonomically as a fungus. Fungal therapy had
already been attempted with amphotericin B for the treatment of aspergillosis. The occurrence of
Pseudomonas aeruginosa infections as a corollary to cystic ibrosis has engendered considerable
interest in antibiotic aerosol therapy. Initial work on amikacin products has resulted in the develop-
ment of the tobramycin aerosol treatment (Novartis), which was the irst aerosol antibiotic approved
in the United States. 23 A monobactam antibiotic, aztreonam, is now available in a nebulizer formu-
lation as Cayston and was approved by the FDA in February, 2010. It was reformulated as the lysine
salt to reduce post-inhalation inlammation. Sputum taken after nebulization showed that it retained
its antimicrobial properties. 23-25