Case Study: Advair/Seretide Flashcards
(29 cards)
When was it launched and who by?
1999 by GSK
What is it a combination of?
fluticasone propionate (Flovent) and salmeterol xinofoate (Serevent)
What is Advair used to treat?
Asthma and COPD
What form is it available in?
A dry powder or aerosol
What is Salmeterol?
A long acting B2-agonist (LABA)
What does activation of B2-receptors do?
Relaxes smooth muscle
What are B2 receptors?
Adrenergic receptors
Where are B2 receptors mostly found?
Bronchial smooth muscle for dilation of airways
What interactions are important for binding?
Pi bonds betwee Phe-290 and drug. H bonds to Asn-293, H bonds to Ser-207 and Ser-204
What happens if you increase the chain length between the ring and N?
It reduces the activity
When is adrenaline used but why is it bad?
In an emergency, is short acting and has no selectivity so will act on adrenergic receptors all over the body
What is good and bad about isoprenaline?
It is selective for B-receptors but not B2 receptors and is short acting
Why is isoprenaline short acting?
Metabolism by COMT enzyme which converts the meta OH phenol to an OMe and inactive metabolite
What modification does Salbutamol have and what does this mean for selectivity?
extra CH2 group before OH group and has the same potency but is 2000 times less active on the heart and lasts 4 hours.
What are the enantiomeric effects of Salbutamol?
R-salbutamol is 68x more active than S but S enantiomer tended to coagulate in tissue so more undesirable side effects though lots of doctors still prescribe the racemate.
Name and describe the benefits of an extension analogue
Salmefamol has 1.5x potency and lasts 6 hours
What is good about Salmeterol?
More lipophilic drug increases duration of action-stronger binding in tissues, accumulates. Has 2x potency and 12 hour duration.
What is fluticasone?
Glucocorticoid and inhaled corticosteroid
What does fluticasone do?
Reduces inflammation in the lungs
What is fluticasone’s mode of action?
It binds to glucocorticoid receptors causing suppression of inflammatory response and increase of anti-inflammatory proteins. reduces blood flow to mucosal linings.
What are the advantages of the combination?
It is the best selling FDC drug, the combined ISC/LABA is now the accepted standard. greater efficacy than just increasing the steroid dose. Synergistic efficacy shown in comparison to use of individual inhalers. Improved patient compliance.
What are the competitors, who made them and what are they?
Symbicort (AstraZeneca) made of Budesonide (ISC) and Formoterol (LABA). Dulera (Merck) made of Mometasone (ICS) and Formoterol (LABA)
Of the ISC and LABA, which is the longer lasting?
ISC
Describe the patent history
Salmeterol patent eexpired 2005 and generic launched in 2011 (TEVA)
patent on active ingredients expired in 2010 (US) and 2013 in UK/EU
Still selling over $7b worldwide/year
inhaler devices difficult to copy and patent on the discuss inhaler expired in 2016.
