Drugs acting on the adrenergic nervous system Flashcards
(118 cards)
1
Q
Adrenergic system makes use of the chemical messengers ______ and ______ .
A
adrenaline, noradrenaline
2
Q
________ is the neurotransmitter released by the sympathetic nerves which feed smooth muscle and cardiac muscle
A
Noradrenaline
3
Q
Adrenaline is a hormone released along with noradrenaline from the ___________.
A
adrenal medulla
4
Q
Adrenaline is a hormone released along with noradrenaline from the ___________.
A
adrenal medulla
5
Q
When is adrenaline released?
A
during times of danger or stress
6
Q
Both the α and the β-adrenoceptors are what type of receptors?
A
G-protein-coupled receptors
7
Q
Adrenergic neurotransmission is responsible for the body’s sympathetic or parasympathetic response?
A
sympathetic
8
Q
The blood vessels supplying skeletal muscle have mainly _______ adrenoceptors and are [constricted/dilated] by adrenaline
A
β2, dilated
9
Q
What is the function of a1 adrenoreceptors?
A
- vasoconstriction
- increased peripheral resistance
- increased blood pressure
- increased closure of internal sphincter of the bladder
10
Q
What are a2 receptors also called?
A
autoreceptors
11
Q
What is the function of a2 receptors?
A
- inhibition of norepinephrine release
- inhibition of acetylcholine release
- inhibition of insulin release
- lowers sympathetic activity
12
Q
What is the function of B1 adrenoreceptors?
A
- tachycardia
- increased lipolysis
- increased myocardial contractility
- increased release of renin
13
Q
What is the function of B2 receptors?
A
- vasodilation
- decreased peripheral resistance
- bronchodilation
- increased muscle and liver glycogenolysis
- increased release of glucagon
- relaxed uterine smooth muscle
14
Q
Both adrenaline and noradrenaline act as?
A
agonists
15
Q
What is the starting precursor for the synthesis of catecholamines?
A
tyrosine
16
Q
L-Tyrosine becomes Levodopa by?
A
hydroxylation with tyrosine hydroxylase
17
Q
Levodopa becomes Dopamine by?
A
decarboxylation with Dopa decarboxylase
18
Q
What does MAO do?
A
oxidation
19
Q
What does COMT do?
A
methylation
20
Q
What happens if reuptake of norepinephrine is prevented?
A
norepinephrine stays longer in the synapse to give a longer duration of adrenergic transmission
21
Q
How is the excess release of norepinephrine prevented?
A
by inhibiting the a2-receptors using norepinephrine (negative feedback inhibition)
22
Q
What is isoprenaline?
A
a powerful β-stimulant devoid of α-agonist activity
23
Q
Norepinephrine is active/inactive, and selective/nonselective
A
active, nonselective
24
Q
What is the effect of adding isopropyl to noradrenaline?
A
- increased selectivity for beta receptor because the beta binding site is big enough for isoprenaline
- decreased activity for alpha receptor
25
Is alpha or beta receptor bigger?
beta receptor
26
What happens if phenol groups are absent in a compound that binds to B-receptors?
activity drops more significantly for β-receptors than for α-receptors
27
How does the addition of an α-methyl group affect the α2-receptor selectivity?
it increases α2-receptor selectivity
28
Effects of a-Methylnoradrenaline?
- lowers adrenergic transmission
| - works similarly to an antagonist but is actually an agonist
29
What does it mean if we design a compound that selectively activated a2 receptors with minimum activity on other receptors?
it means that the compound lowers adrenergic transmission
30
How is the N-alkyl group affected by a polar functional group such as phenol?
the N-alkyl group results in a dramatic rise in activity and selectivity
31
If we add an extra bulky functionality to any compound, it will become more selective for which receptor?
beta receptor
32
What are the advantages of adding a phenol group to the end of an N-alkyl group?
1. higher beta selectivity
2. more active because of more hydrogen bonding interactions
3. higher affinity
33
Adrenaline is administered with local anaesthetics in order to?
to constrict blood vessels and prolong local anaesthetic activity at the site of injection
34
Why is vasoconstriction important when administering local anaesthetics?
because it lowers side effects and prevents the local anesthetic from spreading to other parts of the body
35
What is ephedrine?
- an adrenergic agonist that activates both α− and β-adrenoceptors
- natural product existing as a racemate of the R, S and S, R stereoisomers
36
What is ephedrine used as?
a vasopressor and cardiac stimulant
37
Compare ephedrine to adrenaline
it is more lipophilic than adrenaline so it can cross the
| blood–brain barrier and act as a stimulant
38
Why do ephedrine and pseudoephedrine have lower affinity to alpha and beta receptors?
because they don't have catechols; this results in them having less activity
39
What is Pseudoephedrine?
- adrenergic agonist
| - the S,S diastereomer of ephedrine.
40
What is pseudoephedrine used as?
nasal decongestant
41
Ephedrine and pseudoephedrine are __________ agents.
mixed-action adrenergic
42
What does a mixed-action adrenergic agonist do?
it can switch on the alpha and beta receptors
43
What is dobutamine?
β1-agonist
44
What is dobutamine used for?
treatment of cardiogenic shock
45
What is clonidine?
a selective α2-agonist
46
What is clonidine used for?
treatment of hypertension
47
How does clonidine work?
by decreasing the release of norepinephrine
48
What is oxymetazoline?
selective α1-agonist
49
What is xylometazoline?
selective α1-agonist
50
Both oxymetazoline and xylometazoline act as?
vasoconstrictors
51
Both oxymetazoline and xylometazoline are used in the treatment of?
nasal congestion and bloodshot eyes
52
Compare dobutamine to adrenaline/noradrenaline
dobutamine is structurally similar to adrenaline/noradrenaline except it has an extension
53
What is phenylephrine?
a selective α1-adrenergic receptor agonist
54
What is phenylephrine used as?
decongestant
55
What is the consequence of lacking one OH group in the case of phenylephrine?
less active, lower affinity
56
What is the difference between phenylephrine and norepinephrine?
Phenylephrine has only one OH while norepinephrine has two
57
Isoprenaline shows some selectivity for what receptors?
β-receptors (both 1 and 2)
58
What was the disadvantage of using isoprenaline?
it showed no selectivity between the different subtypes of β-receptors so it also activated the β1-receptors of the heart, leading to unwanted cardiovascular effects
59
How can selectivity between different types of β-receptors be obtained?
- by introducing alkyl substituents to the side chain linking the aromatic ring and the amine
- varying the alkyl substituents on the nitrogen
60
What is isoetharine?
β2-agonist
61
What is the disadvantage of isoetharine?
it was short lasting because the COMT enzyme methylates the catechol and makes it inactive
62
Why is isoetharine more selective for B2?
because the ethyl fits a pocket in the binding site of B2 receptor but has no place in the B1 receptor
63
What is salbutamol?
β2-agonist
64
Compare salbutamol and isoetharine
- CH2 was added between methyl and OH to make salbutamol to protect it from COMT
- salbutamol has the same potency as isoprenaline, but is 2000 times less active on the heart and is more selective for B2
65
How long is the duration of action of salbutamol?
4 hours
66
Is salbutamol taken up by transport proteins or metabolized by COMT?
no
67
Which enantiomer of salbutamol is more active?
R enantiomer
68
What is levalbuterol?
the pure R enantiomer of salbutamol
| B2 agonist
69
Can COMT methylate R-Salbutamol?
no because it is not a catechol anymore
70
What is salmefamol?
B2 agonist
71
Compare salmefamol to salbutamol
salmefamol is 1.5 times more active than salbutamol and has a longer duration of action (6 hours)
72
Advantages of R-Salmefamol extension
- more hydrogen bonding
- higher affinity
- higher lipophilicity
73
Why does salmefamol have a longer duration of action?
it is more lipophilic so it binds more strongly with albumin in plasma
74
What is the duration of action of salmefamol?
6 hours
75
Is salmefamol or salbutamol more suitable for treating noctural asthma?
neither
76
What is salmeterol?
B2 agonist that has twice the potency of salbutamol and an extended action
77
What is the duration of action of salmeterol?
12 hours
78
R-Salmeterol is a bioisostere for?
catechol
79
Is R-Salmeterol a COMT substrate?
no
80
What is the most important use for a1?
nasal decongestion by vasoconstriction
81
What is a2 agonist used for?
vasodilation
treatment of hypertension
lowering sympathetic stimulation
82
What is carvedilol?
antagonist at both the α and β adrenoceptors
83
What is labetalol?
antagonist at both the α and β adrenoceptors
84
What are carvedilol and labetalol both used as?
antihypertensives
85
What is carvedilol used for?
treatment of cardiac failure
86
What are a1-antagonists used to treat?
hypertension or to control urinary output
87
What is prazosin?
the first α1-selective antagonist
88
What is the problem with prazosin?
it is short acting
89
Why are doxazosin and terazosin better than prazosin?
because they are given as once-daily doses
90
What drugs have been used for the treatment of benign prostatic hyperplasia?
doxazosin and terazosin
91
______ are being considered as antidepressants
α2–antagonists
92
What is mirtazepine?
α2–antagonist
| antidepressant agent which increases noradrenaline and serotonin levels
93
What was chosen as the lead compound to design β-blockers?
isoprenaline
94
What is pronethalol?
β-blocker that is a partial agonist
95
What was the first β-blocker to be used clinically for angina, arrhythmia, and high blood pressure?
pronethalol
96
What is propranolol?
pure β-antagonist
97
What has greater activity - pronethalol or propranolol?
propranolol
98
What has greater activity - pronethalol or propranolol?
propranolol
99
Which enantiomer of propranolol is the active form?
S-enantiomer although propranolol is used clinically as a racemate
100
What is the importance of having an isopropyl?
increased B-receptor selectivity
101
What is the first non-selective β-antagonist?
propranolol
102
All B1 selective substituents are on ______ position.
para
103
What is more potent, practolol or propranolol?
propranolol
104
What is more potent, practolol or propranolol?
propranolol
105
What is practolol?
a selective cardiac β1-antagonist which does not block vascular or bronchial β2 -receptors
106
Why is practolol much safer than propranolol for asthmatic patients?
because it is more polar and has fewer CNS effects
107
All second-generation beta blockers are?
hydrogen bond acceptors
108
Are first generation beta blockers selective?
no
109
Are second generation beta blockers selective?
yes
110
What is esmolol?
second generation B-blocker that has rapid onset of action
111
Why is esmolol short-acting?
it contains ester that is easily hydrolyzed
112
What is esmolol used for?
it is administered if the heart starts to beat too rapidly, especially during surgical procedures
113
α-methyltyrosine inhibits?
tyrosine hydroxylase (regulatory enzyme for catecholamine biosynthesis)
114
_______ is sometimes used clinically to treat tumour cells which overproduce catecholamines (e.g., Pheochromocytoma)
α-methyltyrosine
115
____________ are used as a way of downregulating the adrenergic system
false transmitters
116
Are false transmitters more or less active than noradrenaline?
less
117
Is a-Methylnoradrenaline a neurotransmitter?
no
118
__________ was once prescribed as an antihypertensive agent, but it has serious side effects (e.g. depression). Therefore, it is no longer used.
reserpine
