lecture 4 Flashcards
1
Q
Norepinephrine and epinephrine structure difference
A
Epinephrine has extra CH3 group
2
Q
Monoamine structure
A
contains 1 amino group connected to aromatic ring by two carbon chain
3
Q
Catecholamine structure
A
Aromatic ring with two OH groups
4
Q
rate limiting step in cathecholamine biosynthesis
A
Tyrosine hydroxylase
5
Q
Biosynthesis of catecholamine steps
A
- Tyrosine will have OH added by tyrosine hydroxylase to form L-DOPA
- L-DOPA loses COOH by decarboxylase to form dopamine
- Dopamine hydroxylase adds OH to form norepinephrine
- Adrenal medulla adds CH3 to form epinephrine
6
Q
Inhibitory for rate limiting step for cathecholamines
A
Metyrosine
7
Q
Inhibitor of decarboxylase step in catecholamine synthesis
A
Carbidopa
8
Q
Dopamine is transported into vesicle by________
A
VMAT
9
Q
NE binds_____ on post synaptic and _____ on pre synaptic
A
Adrenergic receptor
regulatory receptor
10
Q
NE is re-uptaken by
A
Norepinephrine transporter
11
Q
NE is metabolized by_______
A
MAO and COMT
12
Q
Where is COMT found?
A
highest activity in liver.
13
Q
Where is MAO found in highest concentrations?
A
nerve terminal, liver
14
Q
Stereochemistry required for norepinephrine with adrenergic receptors interaction
A
Only R isomer in B carbon can have a strong affinity to receptor.
15
Q
A1 receptor action on blood vessels
A
Vasoconstriction (innervated)
16
Q
A1 receptor action on pupils
A
Dilation
17
Q
A1 receptor action on vas deferens
A
Ejaculation
18
Q
A1 receptor action on GI tract
A
GI inhibition
19
Q
A2 receptor effect on blood vessels
A
Vasoconstriction (uninnervated)
20
Q
main use of a2 receptor
A
pre-junctional inhibition of NE release
21
Q
A2 receptor use in CNS
A
reduce SNS in[ut
22
Q
B1 receptor use in cardiac system
A
cardiac stimulation
23
Q
B1 receptor use in kidney
A
Secretion of renin
24
Q
B2 receptor use in general
A
RELAXATION
25
B2 effect on lungs
Bronchodilation
26
B2 effect on vasculature
Vasodilation
27
B2 effect on bladder
Relaxation
28
Which neurotransmitter acts on a1, a2, and B1 but not B2
Norepinephrine. Epinephrine works on all.
29
Why does epinephrine bind B2 but not norepinephrine
methyl added to epi makes it easier to bind.
30
Is epinephrine more selective to B or A
Beta
31
2 direct acting adrenergic recetpro agonists
Norepinephrine and epinephrine
32
Norepinephrine is a potent agonist for which receptors
A and B1
33
Why is Norepinephrine only IV and not oral
It is broken down by MAO and COMT. (First pass effect will be metabolized by liver.)
34
What receptors are targeted at lower concentrations of epinephrine
B1 and B2
35
Clinical use of epinephrine
Treats acute anaphylaxis or cardiac arrest
36
Why is epinephrine also not orally available
First pass effect
37
Norepinephrine effect on A1
Vasoconstriction
38
Norepinephrine effect on B1
increases cardiac force and conduction.
39
epinephrine effect on B2
Vasodilation and bronchodilation
40
Dopamine effect on renal system
Vasodilation
41
Dopamine effect on a1
Vasoconstriction
42
Clinical use of dopamine
Shock, acute heart failure (IV)
43
what is dobutamine
Dopamine derivative
44
Why does dobutamine need to be a racemic mixture
Leads to selective inotropic effect on heart rather than a chronotropic effect
45
Why does dobutamine have an inotropic effect rather than chronotropic
+ enantiomer is a potent B1 receptor agonist
- enantiomer is a potent A1 receptor agonist
46
a1 signaling pathway and mechanism
Gq- Mobilizes intracellular Ca2+ to activate PKC
47
a1 agonist clinical use
Nasal decongestion
Vascular failure and tachycardia
48
a1 antagonist clinical use
HTN
BPH
pheocromocytoma
49
structural difference between epinephrine and phenylephrine
Phenylephrine lacks 1 OH group
50
Effect of lack of OH group in phenylephrine compared to epinephrine
Gives phenylephrine a1 selectivity
51
clinical use of phenylephrine
nasal decongestant
mydriasis
vasoconstriction in anesthesia
52
is phenylephrine a substrate for MAO and COMT?
MAO yes, not COMT
53
What effect does imidazoline being charged have on its PH
Makes it more basic.
54
What pathway does A2 have and state its mechanism
Gi pathway. Inhibits adenylyl cyclase and inhibits neuronal Ca2+
55
Where in the synaptic system is a2 found? What is its function there?
It is found pre synaptically and functions as an autoreceptor to inhibit sympathetic output
56
How does a2 inhibit sympathetic output
Acts as an autoreceptor. It is a feedback inhibitor.
57
a2 agonist clinical use
HTN
pain
glaucoma
58
a2 agonist drugs structures?
clonidine, apraclonidine, methyldopa, guanabenz, guanafacine, brimonidine
59
use of the 2 Cls in clonidine
Since Cls are electron withdrawing, this lessens the PKA. This increases CNS access.
60
activation a2 receptors in CNS ________ SNS activity
Decrease
61
side effects of a2 agonist
hypotension, sedation, dry mouth
62
effects of a2 on CNS
a2 limits sympathetic output. This decreases HR and renin release.
63
example of a2 agonists with open ring imidazoline
guanabenz, guanafacine
64
a2 agonist with shortest half life
Guanabenz
65
why is methyldopa a prodrug and not a drug
Methyldopa has CNS access. It is transformed to methylnorepinephrine on action site.
66
the pro drug methyl dopa is transformed to
methylnorepinephrine
67
difference in water solubility between methyldopate and methyldopa
Methyldopate has good water solubility
methyldopa does not.
68
why is methyldopa oral
non-water soluble
69
why is methyldopate parenteral?
is highly soluble
70
Brimonidine clinical use
Glaucoma
71
how does brimonidine treat glaucoma
inhibits aqueous humor production
72
What drug has para NH2 on clonidine
Apraclonidine
73
Effect of para NH2 on apraclonidine
increases PKA
74
B1 found in
heart and kidney
75
B1 effect on heart
increase force, HR and conduction
76
B1 effect on kidney
Increase renin release
77
B1 agonist use
shock, congestive HF
78
B1 antagonist use
hypertension
angina
arrythmia
congestive HF
79
B2 generally used for
Relaxation
80
B2 agonist clinical use
Asthma, premature labour
81
B2 antagonist use
Glaucoma
82
B3 found in
urinary bladder
83
B3 agonist use
Overactive bladder
84
B1 selective 2 drugs
Dobutamine, Dopamine
85
B2 selective 2 drugs
Albuterol, Salmeterol
86
Non-selective B agonist drug name
Isoprotorenol
87
Why is isoproterenol more selective for B than A
It has a bulky substitute (just like epinephrine)
88
Clinical use of isoproterenol
Bronchodilation and increase cardiac output
89
Is isoproterenol sensitive to MAO?
No. (can be used oral)
90
reflex tachycardia definition
When BP decreases, heart rate is automatically increased
91
reflex bradycardia definition
increased BP leads to increase in HR
92
why are metaproterenol and terbutaline B2 selective
Position of OH in catechol ring is different
93
Are metaproterenol and terbutaline metabolized by MAO and COMT
No
94
why is albuterol B2 selective
hydroxy methyl instead of hydroxy
95
Side effects of B2 agonist drugs
Minor cardiac output in high doses
96
indirect acting sympathomimetics example
Ampthetamines, cocaine
97
How does amphetamine indirectly affect NE concentration
Amphetamines reverse norepinephrine transporters. This is why they act so long.
98
How does cocaine affect the Norepinephrine
Cocaine completely blocks the norepinephrine transporters from reuptaking the neurotransmitter from the cleft.
99
Why doesn't amphetamine bind to adrenergic receptor
lacks catechol. (Also the reason it is not metabolized by COMT)
100
Is amphetamine susceptible to MAO? why or why not
No. Methyl group on amphetamine interferes.
101
how do we treat amphetamine/methamphetamine overdose
Acidify urine to increase excretion
102
why does ephedrine have a direct A and B agonist activity on adrenergic receptors
Has R configuration
103
Why does ephedrine have A and B agonist activity, but not pseudoephedrine.
R-config at B-OH in ephedrine. S config in pseudoephedrine reduces agonist activity
104
Biggest caution when taking ephedrine and pseudoephedrine
DO not use if taking MAO-inhibitors
105
Why avoid MAOI when taking ephedrine and pseudoephedrine
NE will not be degraded, giving a strong sympathetic response.
106
Action of cocaine
Blocks NET, decreases reuptake, enhances NE signaling by keeping more neurotransmitters in cleft
107
Side effects of cocaine
Increase BP and HR
108
methylphenidate action
blocks NE and dopamine reuptake.
109
Use of methylphenidate
ADHD, narcolepsy
110
Atomoxetine action
inhibits NET
111
Issues for atomoxetine
Blackbox indication for suicidal ideation
