W20 - Lung Medication

Question 1

what does understanding and probing structure activity relationships involve

Answer 1

studies to determine the atoms or functional groups that are important to a drugs activity

Question 2

what can these studies lead to

Answer 2

identification of the pharmacophore

groups that are identified to be essential for activity

Question 3

What is the relevence of beta 2 adrenoreceptor in the treatment of asthma

Answer 3

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.

Question 4

what were the natural starting point for the development of adrenergic beta 2 agonists

Answer 4

adrenaline and noradrenaline

Question 5

what are some examples of beta 2 agonists

Answer 5

salbutamol dobutamine and xamoterol

Question 6

what molecular target are adrenergic receptors

Answer 6

G protein linked receptors

Question 7

what is the importance of serine in relationship to adrenaline and noradrenaline

Answer 7

serine residue interacts with the phenolic groups of the catecholamine via hydrogen bonding

Question 8

what is the importance of the aromatic ring of the phenylamine residue in relationship to adrenaline and noradrenaline

Answer 8

interacts with the catechol ring via van der waals interactiosn

Question 9

what is the importance of the aspartic residue in relationship to adrenaline and nor adrenaline

Answer 9

interacts with the protonated nitrogen of the catecholamine by ionic bonding

Question 10

why is adrenaline no longer used to treat asthma

Answer 10

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

Question 11

what was adrenaline replaced by

Answer 11

isoprenaline

Question 12

what was the downside of isoprenaline

Answer 12

no selectivity between the different types of beta receptors so side effects still evident

Question 13

how do we provide selectivity to distinguish between the different beta receptors

Answer 13

introducing alkyl substituents to the side chain linking the aromating ring and the amine or varying the alkyl substituents on the nitrogen

Question 14

what is the short duration of isoetharine a result of

Answer 14

drugs being taken up by tissues and methylated by the metabolic enzyme catechol o methyltransferase COMT to form an inactive ether

Question 15

What part of the molecules of isoetharine was the target of COMT

Answer 15

the OH on the phenyl ring.

Question 16

what was essential to note before replacing the meta phenol

Answer 16

the group replacing it is still able to bind to the receptor and retain biological activity

but

would not be recognised by the metabolic enzyme

Question 17

what is chiral swtiching

Answer 17

mostly relates to racemic drugs that have been on the market for several years and are approaching the end of their patent life