2. New Therapies for Asthma & COPD
Dr J. Salamzadeh
Pharm.D., PhD in Clinical Pharmacy
Shahid Beheshti School of Pharmacy

3. Parts of the lecture Available current drugs at a glance New therapies
CFC inhalers vs. HFA-inhalers
Conclusion

4. 1 2 2 3

5. Atrovent ® (Ipratropium bromide)

6. Spiriva Handihaler®
(Tiotropium)

7. Combivent®
Ipratropium Br 20 mcg/puff
Salbutamol sulfate 100 mcg/puff

8. Other currently used drug for asthma & COPD
Zafirlukast: F.C. tab. 10, 20 mg
Intal®: inhalation cap. 20 mg
Xanthines
Theophylline
Aminophylline

9. New therapies Alvesco® (ciclesonide) (2006)
a prodrug ……………… the active metabolite
desisobutyryl-ciclesonide (des-CIC)
a corticosteroid preventer
high lipophilicity
creating a reservoir capable of
releasing active metabolite from lung epithelial cells
prolonged anti-inflammatory effects
once-daily-dosing
high protein binding (99%)
low oral bioavailability (<1%)
Limited systemic side-effects
سيكلزونايد (80 و 160 mcg/puff) به شرط تولید در داخل کشور و انجام مطالعه بالینی به ليست دارويي كشور اضافه شده است!

10. New therapies Spiriva ® (Tiotropium bromide)
Spiriva Handihaler ® inhalation powder (cap.)
for the long-term, once-daily, maintenance treatment of bronchospasm associated with COPD (2004), and for reducing COPD exacerbations (2009).
Spiriva Respimat ® inhalation solution
maintenance bronchodilator treatment to relieve symptoms of COPD, once a day, 2 puffs.
One cartridge contains 4.0 ml providing 60 puffs (30 medicinal doses).

11. New therapies Omalizumab (Xolair ®) (2003)
a recombinant humanised anti-IgE monoclonal antibody
Indication: prophylaxis of allergic asthma not responding to high-dose inhaled corticosteroids + long-acting beta2 agonist, in adults and > 12 yrs. as add-on therapy.
2009 (EMA): as an add-on therapy for severe persistent allergic asthma in children between the ages of 6 and 11 years.

12. New therapies Indacaterol inhalation cap.
Onbrez® Breezhaler (EMA, 2009)
Arcapta® Neohaler (FDA, 2011)
is an ultra-long-acting beta-adrenoceptor agonist (ultra-LABA).
half-life ranging from 45 to 126 hours.
Duration of action: >24 hrs.
licensed only for the maintenance treatment of COPD.
EMA: European Medicines Agency

13. New therapies
Daliresp® , Daxas® (Roflumilast) (2011)
is an oral tablet to reduce COPD exacerbations.
to be taken once daily.
the mechanism of action:
acts as a selective, long-acting inhibitor of the enzyme PDE-4:
to increase intracellular cAMP in lung and immune cells.
anti-inflammatory effect.
a major limitation:
side effect profile: nausea, headaches, and diarrhea.
PDE-4 inhibitors are a potentially important new class of agents for COPD.
PDE-4: phosphodiesterase 4

14. New therapies
Tudorza® Pressair® & Eklira® Genuair® (Aclidinium bromide inhalation powder) (2012)
is an anticholinergic drug.
contains a dry powder formulation.
for long-term maintenance treatment of COPD.
is administered 400 mcg twice a day.

15. Specific advantages of Aclidinium bromide
long-lasting activity at M3 receptors
fast onset of action
rapid plasma clearance/hydrolysis (t1/2= 2.4 min. in human plasma)
sustained bronchodilation
very low and transient systemic side-effects

16. Aclidinium bromide Not to be confused with Clidinium bromide.

17. New therapies Breo Ellipta® GSK (2013)
fluticasone furoate (100mcg) and vilanterol (25 mcg) (ultra-LABA)
an inhalation powder.
for the treatment of COPD.
used as once a day inhalation.

18. Joint project by GSK & Amira Pharmaceuticals
New therapies
Inhibitors of 5-lipoxygenase activating protein (FLAP)
inhibiting the synthesis of pro-inflammatory leukotrienes.
Indication:
Inflammatory disorders e.g. asthma.
patent drugs under clinical trials : AM103; AM803
Joint project by GSK & Amira Pharmaceuticals

19. HFA Inhalers: New Respiratory Drug Delivery Systems

20. Montreal Convention in 1987
to limit usage of Chloro-fluoro-carbons (CFCs):
1 CFC molecule destroys 100,000 molecule of O3
global phase-out: January 1, 2010
1. Hydro-Fluoro-Alkane (HFA) inhalers
2. Dry Powder Inhalers (DPIs)

21. CFC inhalers vs. HFA inhalers
Do patients will notice any change?
may taste different
may smell different
may feel warmer (no “cold freon effect”)
may be lighter
Technical differences
HFA inhalers have a weaker spray.
HFA inhalers require a slower inhale.
HFA inhalers must be pumped four times (usually) to prime them.
HFA inhalers need to be washed with warm water and air dried once a week.

22. HFA Inhaler; CFC Inhaler;
Softer spray Powerful spray

23. Conclusion
Asthma & COPD are highly complex diseases: numerous inflammatory cells and more than 100 mediators participate in asthma and COPD!!!
so it is unlikely that targeting a single receptor, mediator or risk factor will be highly effective.
It is difficult to discover novel classes of therapy for asthma & COPD, despite intense effort and investment.
None of the currently available treatments for asthma & COPD have long-term effects on airway inflammation or remodeling:
are not disease-modifying or curative.
Patients with severe asthma share several characteristics of patients with steroid resistant COPD:
drugs in discovery for COPD may also be effective in treating severe asthma.

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