Download New therapies

New Therapies for Asthma & COPD
Dr J. Salamzadeh
Pharm.D., PhD in Clinical Pharmacy
Shahid Beheshti School of Pharmacy
Parts of the lecture
•
•
•
•
Available current drugs at a glance
New therapies
CFC inhalers vs. HFA-inhalers
Conclusion
Atrovent ®
(Ipratropium bromide)
Spiriva Handihaler®
(Tiotropium)
Combivent®
– Ipratropium Br 20 mcg/puff
– Salbutamol sulfate 100 mcg/puff
Other currently used drug for asthma & COPD
• Zafirlukast: F.C. tab. 10, 20 mg
• Intal®: inhalation cap. 20 mg
• Xanthines
– Theophylline
– Aminophylline
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
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).
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.
New therapies
• Indacaterol inhalation cap.
– Onbrez® Breezhaler (EMA, 2009)
– Arcapta® Neohaler (FDA, 2011)
– is an ultra-long-acting betaadrenoceptor agonist (ultra-LABA).
• half-life ranging from 45 to 126 hours.
• Duration of action: >24 hrs.
– licensed only for the maintenance
treatment of COPD.
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.
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.
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
Aclidinium bromide
• Not to be confused with Clidinium bromide.
Aclidinium bromide
Clidinium bromide
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.
New therapies
• Inhibitors of 5-lipoxygenase
activating protein (FLAP)

inhibiting the synthesis of proinflammatory leukotrienes.
• Indication:

Inflammatory disorders e.g. asthma.
• patent drugs under clinical trials :
AM103; AM803
Joint project by GSK & Amira
Pharmaceuticals
HFA Inhalers:
New Respiratory Drug Delivery Systems
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)
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.
HFA Inhaler;
Softer spray
CFC Inhaler;
Powerful spray
Conclusion
1) 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.
2) None of the currently available treatments for asthma & COPD have
long-term effects on airway inflammation or remodeling:
 are not disease-modifying or curative.
3) 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.
‫خسته نباشيد‬