Salbutamol/Salmeterol

Question 1

What type of adrenoreceptors does noradrenaline and adrenaline stimulate?

Answer 1

alpha and beta-adrenoreceptors

Question 2

What type of adrenoreceptors does isoprenaline stimulate?

Answer 2

beta-adrenoreceptors

Question 3

where are beta1 receptors found?

Answer 3

in the heart

Question 4

Where are beta2 receptors found?

Answer 4

on bronchial smooth muscle

Question 5

how do we treat bronchoconstriction without affecting the cardiovascular system?

Answer 5

using drugs that only stimulate beta2 receptors for bronchodilation

Question 6

how are the airways in asthmatic patients characterised?

Answer 6

1. inflammation (swelling and thick mucus production)

2. bronchospasm (bronchoconstriction, narrow airways)

Question 7

what system causes bronchoconstriction?

Answer 7

the cholinergic system

Question 8

what system causes bronchodilation?

Answer 8

the adrenergic system

Question 9

what drug is used as an adrenergic agonist to stimulate bronchodilation?

Answer 9

salbutamol

Question 10

what drug is used as an inhaled corticosteroid to treat inflammation?

Answer 10

beclometasone

Question 11

How does inflammation occur?

Answer 11

1. Antigen binds to Antibody (IgE)
2. A-A complex forms
3. Bronchoconstricting mediators (mast cells) arrive at site
4. prostaglandin, histamine and leukotrienes released by mast cells

Question 12

What is used to inhibit the cholinergic system?

Answer 12

anticholinergics

Question 13

what are noradrenaline and adrenaline classified as?

Answer 13

Catecholamine

Question 14

where is noradrenaline synthesised?

Answer 14

in neurons of both CNS and autonomic nervous system

Question 15

how is a transmission terminated?

Answer 15

1. stimulated adrenergic neurons release noradrenaline into synaptic cleft producing a characteristic adrenergic response
2. presynaptic neurones are taken in causing termination
3. some noradrenaline also diffuses away from the receptor and is metabolised by catechol-O-methyltransferase (COMT) or by monoamine oxidase (MAO) in circulatory system or COMT in other tissues
4. noradrenaline can also be used again or metabolised by mitochondrial MAO

Question 16

what are the two types of central nervous systems?

Answer 16

somatic and autonomic

Question 17

What are the two types of autonomic nervous systems?

Answer 17

sympathetic and parasympathetic

Question 18

where do drugs target in the release of noradrenaline and its transmission?

Answer 18

1. enzymes in noradrenaline biosynthesis
2. vesicles carrying noradrenaline
3. exocytosis of vesicles with cell membrane
4. adrenergic receptors
5. transport protein for noradrenaline
6. metabolic enzymes
7. presynaptic receptors

Question 19

How do adrenoreceptors affect biological activity?

Answer 19

they release secondary messenger molecules inside the cell after binding to an extracellular agonist

Question 20

what three bonds does noradrenaline make with adrenoreceptors?

Answer 20

1. ionic bonds
2. hydrogen bonds
3. van der Waals

Question 21

What type of effect do esters and amides have on beta receptors?

Answer 21

they’re beta-antagonists

Question 22

What derivative is salbutamol?

Answer 22

a salicylamine derivative

Question 23

what determines whether the drug is alpha or beta adrenoreceptor selective?

Answer 23

the substituents on the amine group

Question 24

What three characteristics must the substituents on the benzene ring have to exhibit beta2-receptor activity?

Answer 24

1. the phenolic hydroxy group should be in the para position
2. the substituent in the meta position should be able to take part in H-bonds
3. the ring configurations are resistant to COMT metabolism

Question 25

how can we increases the time the drug is effective for?

Answer 25

1. make resistant to metabolism and low plasma clearance. (change pharmacokinetic properties)
2. re-formulate (delayed release instead of IR)
3. make it a pro-drug (becomes active when metabolised)

Question 26

How do LABA’s (Long Acting Beta2-Agonist) work?

Answer 26

1. bind in the vicinity of the beta adrenoreceptor for longer
2. has 2 sites of interaction (active site and a non-polar region)

Question 27

which is longer acting salbutamol or salmefamol?

Answer 27

Salmefamol

Question 28

To obtain a long drug potency what range does the cLogP value have to lie within?

Answer 28

3.3-4.5

Question 29

To maintain potency, how many carbons should be between N and O and between C and O in the Salbutamol structure?

Answer 29

between N and O = 5-6 carbons
between C and O = 2-4 carbons
(slide 34)

Question 30

what is the exo-site hypothesis?

Answer 30

the concept that the long side chain of salbutamol (exo-site) interacts with the non-polar region of the cell membrane within the vicinity of the beta receptor.