Biomedical Engineering Reference
In-Depth Information
treatments. However, progress is underway and there are several classes of
drug that are now in preclinical and clinical development (2,3).
II.
SMOKING CESSATION
Cigarette smoking is the major cause of COPD in the world and smoking
cessation is the only therapeutic intervention so far shown to reduce disease
progression. Nicotine addiction is the major problem and treatment should
be directed at dealing with this addictive state. Nicotine replacement thera-
pies have not proved to be very effective and do not deal with the underlying
addictive state. An important advance has been the discovery that a short
course of the atypical antidepressant bupropion is an effective adjunct for
smoking cessation in patients with COPD (12). However, the relatively poor
long-term quit rate (16% at 6months) means that more effective approaches
are needed. Bupropion is an antidepressant that has effects on noradrenergic
pathways, and other drugs with a similar profile are now in development.
There is a much better understanding of the neurobiology of nicotine
dependence and some of the central neurotransmitters that are involved
(13). Neural mechanisms involved in nicotine addiction include dopaminer-
gic pathways in the nucleus accumbens (14), but serotoninergic and glutami-
nergic pathways are also involved. New approaches to treating nicotine
addiction include cannabinoid CB
1
-receptor antagonists, GABA
B
-receptor
agonists, metabotropic glutamante (mGlu
5
) receptor agonists, dopamine
D3-receptor antagonists, serotonin 5-HT
1A
-receptor antagonists, and
agonists of the
b
2-subunit of nicotinic receptors. Another development is vac-
cines against nicotine developed by immunizing with a nicotine hapten linked
to an immunogenic protein that results in sequestration of nicotine to prevent
its entry into the brain (15). These vaccines are now in clinical development.
III. NEW BRONCHODILATORS
Since bronchodilators are the mainstay of current management (16), a
logical approach is to improve existing bronchodilators. Several once-
daily-inhaled
b
2
-agonists are now in clinical development, and the
once-daily-inhaled anticholinergic tiotropium has recently become available
in several countries (17). Long-term studies with tiotropium bromide have
demonstrated significant improvement in symptoms and improvement in
the quality of life, as well as an unexpected reduction in exacerbations
(18). Tiotropium is likely to have additive effects when combined with
long-acting
b
2-agonists making once daily combination bronchodilator
inhalers a likely development (19). New classes of bronchodilator, such as
potassium channel openers and phosphodiesterase-3 inhibitors, have been
difficult to develop as the side effects, particularly vasodilator effects,
usually limit the dose.
