Beta Blockers

Question 1

What are the two main types of cardiovascular drugs that are commonly prescribed in northern Ireland

Answer 1

Beta Adrenoreceptor blocking drugs
Calcium channel blockers

Question 2

What are Adrenoreceptors

Answer 2

Adrenoreceptors are receptors that mediate the central and peripheral actions of the neurotransmitter noradrenaline and hormone and neurotransmitter adrenaline.
These receptors are responsible tovregujate the autonomic nervous system.

Question 3

Where are Adrenoreceptor found

Answer 3

Nearly all peripheral tissues
Many neuronal populations in CNS

Question 4

Types of Adrenoreceptor

Answer 4

A1 a1 b123

Question 5

What Adrenoreceptors predominate in the heart

Answer 5

B1

Question 6

What is the group are noradrenaline and adrenaline c

Answer 6

Catecholamines

Question 7

Structure activity relationships in neurotransmitter

Answer 7

Benzene ring - going to be involved in VDW interactions with the avfuve site
Multiple OH group- involved in h bonding
r e antiomer is more active than the s
N group may be charged - allowing for ionic bonding to receptor site
1 or 2 alkyl substiteunts required - larger substitents increase selctity for b receptors

Question 8

Alcoholgroup

Answer 8

Shows that the r e at Aimee is more active than s
Secondary alcohol involved in h bonding
Still has activity without but reduced interaction - alcohol group important but not essential

Question 9

Amine group

Answer 9

Normally portanted and ionised at physiological pH
It is important because if N is replaced with carbon there is decreased activity
Larger, bulkier substituents increase selectivity for b receptors ( more likely to bind to hydrophobic pocket )/

Question 10

Both phenol substitents

Answer 10

Important. Both involved in H bonding. Can be replaced by other groups capable of H bonding with the active site.

Question 11

Alkyl substitution

Answer 11

Alkyl substitution on side chain linking aromatic ring to amine will decrease the activity of both a and b Adrenoreceptors .
This may be a steric affect which blocks hydrogen bonding with the Molecule or the molecule adapting active conformation.

Question 12

Difference between a and b Adrenoreceptors

Answer 12

B Adrenoreceptors have a hydrophobic pocket. In order to achieve the selectivity for b you can include bulky sunstutuents in amide.

Question 13

Structure activity bb first gen

Answer 13

Branched bulky n alkyl substitents are good for B antagonist activity , suggesting an interaction with the hydrophobic pocket in the binding site.

Variation of the aromatic ring systems is possible and heteroaromstic rings can be introduced.

Substitution in the side chain methylene group increase metabolic stability but lowers stability p

Alcohol group on the side Chain is essential for activity

Replacing ether oxygen on the side chain with s, ch2 or nch3 is detrimental

N alkyl substitents > isopropyl or t butyl are less efefectuve , branching is beneficial to fit b hydrophobic pocket

Question 14

What do first generation bb act against

Answer 14

B1 and b2 Adrenoreceptor

Question 15

Second gen bb

Answer 15

B1 selective (suitable for asthma patients as b2 constructs airways )
Amide group is in the para position which allows for extra h binding interacting with B1 and providing selcectivity
Makes molecuke more polar / less likely to cross bbb and cause cns effects

Question 16

Example of second gen bb

Answer 16

Practolol

Question 17

Third generation bb

Answer 17

Chain extension with N arylalkyl group
Not all necessarily B1 zwlctive
Extra vasodilation g properties by blocking alpha adrenergic receptors or nitric oxide release

Question 18

Example of bb 3rd gen

Answer 18

Carvediol nebivolol