W20 - Lung Medication Flashcards
what does understanding and probing structure activity relationships involve
studies to determine the atoms or functional groups that are important to a drugs activity
what can these studies lead to
identification of the pharmacophore
groups that are identified to be essential for activity
What is the relevence of beta 2 adrenoreceptor in the treatment of asthma
beta 2 adrenoreceptor activation leads to smooth muscle relaxation and since they line the bronchial smooth muscle this leads to dilation of the airways which is important for the treatment of asthma.
what were the natural starting point for the development of adrenergic beta 2 agonists
adrenaline and noradrenaline
what are some examples of beta 2 agonists
salbutamol dobutamine and xamoterol
what molecular target are adrenergic receptors
G protein linked receptors
what is the importance of serine in relationship to adrenaline and noradrenaline
serine residue interacts with the phenolic groups of the catecholamine via hydrogen bonding
what is the importance of the aromatic ring of the phenylamine residue in relationship to adrenaline and noradrenaline
interacts with the catechol ring via van der waals interactiosn
what is the importance of the aspartic residue in relationship to adrenaline and nor adrenaline
interacts with the protonated nitrogen of the catecholamine by ionic bonding
why is adrenaline no longer used to treat asthma
short duration of action
no selectivity for b2 receptors as it swtiches on all possible adrenergic receptors
leading to side effects mainly in the cardiovascular system
what was adrenaline replaced by
isoprenaline
what was the downside of isoprenaline
no selectivity between the different types of beta receptors so side effects still evident
how do we provide selectivity to distinguish between the different beta receptors
introducing alkyl substituents to the side chain linking the aromating ring and the amine or varying the alkyl substituents on the nitrogen
what is the short duration of isoetharine a result of
drugs being taken up by tissues and methylated by the metabolic enzyme catechol o methyltransferase COMT to form an inactive ether
What part of the molecules of isoetharine was the target of COMT
the OH on the phenyl ring.