ANS Harvey Part 3 Flashcards
1
Q
are a class of compounds that include the endogenous neurotransmitters and hormones released by adrenergic neurons in the sympathetic nervous system.
A
catecholamines
2
Q
are exogenous compounds that imitate the functional responses produced by endogenous catecholamines
A
sympathomimetics
3
Q
are exogenous compounds that block the functional responses to endogenous catecholamines or sympathomimetics.
A
sympatholytics
4
Q
In order to understand what kind of response a catecholamine or sympathomimetic produces, it is important to know:
A
the type of adrenergic receptor involved
the type of cell and/or tissue involved
the signaling pathway activated by that receptor
whether or not the effects are direct and/or indirect
5
Q
What does alpha 1 adrenergic receptors do?
A
utilize Gq which binds to PLC->PIP2 Dag IP3-> Ca2. Present in smoothe muscle contractions
6
Q
Where are alpha adrenergic receptors found?
A
location – smooth muscle blood vessels eye (iris radial muscle) bladder (sphincter muscle) skin (piloerector muscles)
7
Q
What is the signaling mechanism of alpha 1 adrenergic receptors?
A
Gq activation of phospholipase C
8
Q
What is the the response of activated alpha 1 adrenergic receptors?
A
contraction
9
Q
Summarize Alpha I adrenergic receptors
A
Gq-> IP3-> Ca2+-> smooth muscle contraction
10
Q
alpha adrenergic α2 receptors are located where?
A
some vascular smooth muscle
central and peripheral presynaptic nerve terminals
11
Q
What is the signaling mechanims of alpha adrenergic α2 receptors?
A
Gi/o inhibition of adenylyl cyclase
Gi/o inhibition of presynaptic Ca2+ channels
12
Q
What is the response of alpha adrenergic α2 receptors?
A
vasoconstriction
inhibition of neurotransmitter release
13
Q
How does alpha adrenergic α2 receptors create vasoconstriction?
A
It inhibits cAMP (cAMP inhibits contractions) via inhibition of adenylul cyclase
14
Q
How does alpha adrenergic α2 receptors inhibit neurtransmitter release?
A
Alpha 2 inhibit calcium channels through activation of Gi/Go and their beta subunits inhibit Ca channels.
15
Q
Where do you find beta adrenergic β1 receptors?
A
heart
kidney
adipose tissue
16
Q
What is the signaling mechanism of beta adrenergic β1 receptors?
A
– Gs activation of adenylyl cyclase
17
Q
What is the response of beta adrenergic β1 receptors?
A
heart
increase firing rate (sinoatrial node)
increase conduction velocity (atrioventricular node)
increase contractility (ventricular muscle)
increase rate of relaxation (ventricular muscle)
kidney – increase renin secretion
adipose tissue – lipolysis
18
Q
What is positive chronotropic effect?
A
increase firing rate of heart
19
Q
What is positive dromotropic effect?
A
increase conduction velocity
20
Q
What is positive inotropic effect?
A
increase contractility
21
Q
What is positive lusitropic effect?
A
Increase rate of relaxation
22
Q
release of (blank)leads to an increase in angiotensin II production
A
renin
23
Q
What is the location of beta adrenergic β2 receptors?
A
location cardiac muscle smooth muscle -vascular -airway -gastrointestinal -bladder (detruser muscle) -uterus Skeletal Muscle, Liver
24
Q
What is the signaling mechanism of beta adrenergic β2 receptors?
A
Gs activation of adenylyl cyclase
25
What is the response of beta adrenergic β1 receptors?
increase heart rate and contractility
relax smooth muscle
increase glycogenolysis
26
β2-receptor activation stimulates (blank)
glycogenolysis
27
beta adrenergic β3 receptors
location – ?
signaling mechanism – ?
response – ?
adipose tissue
Gs activation of adenylyl cyclase
lipolysis
28
What are juxtaglomeular cells?
receive sensory information of sympathetic system which makes them release renin
29
dopaminergic D1-5 receptors
Location--?
Signaling pathway--?
Response---?
vascular smooth muscle (kidney)
central nervous system
D1/5 Gs activation of adenylyl cyclase
D2-4 Gi inhibition of adenylyl cyclase
vascular smooth muscle - relaxation
central nervous system
control of motor movement
regulation of prolactin secretion
30
D1-5 receptors in the vascular smooth muscle (kidney) utilizes D1 & D5 to activated Adenylyl cyclase with what G protein?
Gs
31
D2-4 receptors in theCNS utilizes D2-D4 to activated Adenylyl cyclase with what G protein?
Gi
32
It is important to recognize that it is not uncommon to actually find (blank) adrenergic receptors in any given cell type.
more than one type of
33
All the receptors discussed so far may also be involved in regulating (blank) not discussed here.
other signaling pathways
34
The ability of a given type of receptor to regulate multiple signaling pathways can, in some cases, be explained by the fact that there are further (blank) for some of these receptors
subclassifications
35
catecholamines consist of 2 moieties?
catachol and an ethylamine side chain
36
What has a benzene ring with hydroxyls at the 3 (meta) and 4 (para) positions?
catechol
37
The α and β carbons of the ethylamine moiety of catecholamines are (blank) carbons.
chiral
38
Therefore, substitutions at the α and β ethylamine moiety sites result in (blank). This includes enantiomers (mirror images) if there are substitutions at just one carbon and (blank) (non-mirror images) if there are substitutions at both carbons.
For catecholamines with β carbon substitutions, the l-isomers are the most biologically active form. Endogenous catecholamines only exist as (blank)
stereoisomers
diastereomers
l-isomer.
39
(sympathomimetics) Compounds that mimic the responses produced by sympathetic stimulation can be divided into three different categories; what are they?
direct, indirect, mixed
40
(blank) produce their effects by directly activating adrenergic receptors. Endogenous catecholamines belong to this class.
Direct acting compounds
41
(blank) produce their effects by increasing the availability of endogenous catecholamines. This can be achieved by:
inhibiting reuptake
stimulating release
inhibiting metabolism
Indirect acting compounds
42
(blank) compounds produce their effects by both direct and indirect mechanisms.
Mixed
43
Direct acting sympathomimetics will have substitutions on at least 2 of the following 3 positions: What are they?
the meta position on the benzene ring,
the para position on the benzene ring, or
the beta carbon of the ethylamine side chain, and it must be a hydroxyl.
44
With direct acting compounds for sympathomimetics:large substitutions on the terminal nitrogen tend to promote (blank)
small substitutions tend to promote (blank)
β adrenergic receptor activity
| α adrenergic receptor activity.
45
Hyroxyl substitutions on the 3 and 5 positions of the benzene ring tend to enhance (blank)
β2 adrenergic receptor selectivity.
46
Indirect acting sympathomimetics will have (blank) at either the meta or para postion of the benzene ring or the beta-carbon of the ethylamine side chain.
none or only 1 substitution
47
(SYMPATHICMIMETICS WITH INDIRECT ACTIVITY) For sympathomimetics with (blank), both d- and l- isomers may be active. For example:
ex )Amphetamine, Ephedrine
α carbon substitutions
48
(SYMPATHICMIMETICS WITH INDIRECT ACTIVITY) With indirect acting compounds, a lack of substitutions on the benzene ring and the (blank) increase the ratio of central effects (e.g., amphetamine) to peripheral effects (e.g., phenylpropanolamine).
β carbon
49
(SYMPATHICMIMETICS WITH INDIRECT ACTIVITY) If (blank) are missing at either the 3 or 4 positions of the benzene ring, the compound is not a substrate for metabolism by COMT, and the duration of action tends to be longer.
hydroxyls
50
(SYMPATHICMIMETICS WITH INDIRECT ACTIVITY) A substitution (usually a methyl group) on the (blank) reduces the ability of the compound to be metabolized by MAO, and the duration of action tends to be longer. Non-catechols with an α carbon methyl group tend to be very long acting (e.g., amphetamine)
α carbon
51
```
Imadazolines are a class of sympathomimetics that contain an imidazole moiety. Many of these compounds are potent (blank) used as vasoconstrictors in topical over the counter nasal and ophthalmic preparations.
Oxymetazoline-activates
```
α agonists
| alpha 1 and 2 receptors
52
What is an important sympathomimetic with indirect activity?
amphetamine
53
What are the order of affinity for agonist for Alpha 1 receptor?
Epi ≥ NE >> Iso
| phenylephrine
54
What are the order of affinity for agonist for Alpha 2 receptor?
Epi ≥ NE >> Iso
| clonidine
55
What are the order of affinity for agonist for Beta1 receptor?
Iso > Epi = NE
| dobutamine
56
What are the order of affinity for agonist for Beta 2 receptor?
Iso > Epi >> NE
| terbutaline
57
What are the order of affinity for agonist for Beta 3 receptor?
Iso = NE > Epi
58
When would you use aympathomimetics?
```
Cardiovascular applications (acute hypertension), respiratory system applications (asthma), anaphylaxis
Opthalmic applications (glaucoma)
Genitourinary Applications (preterm labor)
CNS (muscle relaxation)
```
59
```
What can be used therapeutically for these issues?
Cardiovascular Applications
-Acute hypotension
-Chronic orthostatic hypotension
-Hypertension
-Cardiac Applications
-heart block
-heart failure
-Local vasoconstriction
```
Respiratory System Applications
- Bronchial Asthma
- Chronic obstructive pulmonary disease
- Decongestion
Anaphylaxis
sympathomimetics
60
```
What can be used therapeutically for these issues?
Ophthalmic Applications
-Mydriasis
-Decongestion
-Glaucoma
```
Genitourinary Applications
- Preterm labor
- Incontinence
Central Nervous System
- Narcolepsy
- Attention deficit hyperactivity disorder
- Narcotic withdrawal
- Sedation
- Muscle relaxation
Sympathomimetics
61
What is a therapeutic use of norepinephrine?
hypotension (shock)
62
What receptor does noreinephrine have the most affinity for?
α1≥α2; β1>>β2
63
What are the cardiovascular responses of norepinephrine (a1 and b2)?
increase in cardiac output due to increase in contractility (β1)
decrease in heart due to reflex increase in parasympathetic tone
vasoconstriction of most vascular beds (α1)
increase in systolic, diastolic, and pulse pressure, increase in MAP
64
What are the other smooth muscle responses of norepinephrine (a1)
airways, gut, uterus - not much effect (not many α1 receptors).
iris – contraction of radial muscles causes mydriasis
bladder – contraction of sphincter muscle (promotes filling)
65
What receptor does epinephrine have the most affinity for?
α1=α2; β1=β2
66
At low doses of epinephrine which receptor is predominantly activated?
At high doses of epinephrine which receptor is predominantly activated?
beta 2
| alpha 1
67
What is a therapeutic use of epinephrine?
bronchospasms, anaphylactic shock, cardiac arrest, open angle glaucoma, local anesthetic (adjunct)
68
What are the cardiovascular responses of epinephrine (b1 and b2)?
low doses – similar to isoproterenol (β1 and β2)
| high doses – similar to norepinephrine (α1 and β1)
69
What are the other smooth muscle responses of epinephrine (a1 and b2)?
airways – significant dilation (β2)
gut – transient decrease in motility (β2)
bladder – relaxation of detrusor muscle (β2)
contraction of sphincter muscle (α1)
uterus – relaxation (β2)
70
What receptors does dopamine have the most affinity for?
D1-5>β>α
71
What are the therapeutic uses of dopamine?
cadiogenic shock, heart failure
72
What are the cardiovascular responses of dopamin (D1/5, B1 and a1 effects)?
low doses activate D1/5 receptors, increasing renal blood flow and urine production
intermediate doses activate β1 receptors, increasing cardiac output
high doses activation α1 receptors, causing vasoconstriction and increasing BP
73
What are the central effects of dopamine
involved in controlling motor movement in the basal ganglia
| inhibits prolactin secretion in the anterior pituitary
74
What are these fenoldopam, bromocriptine, levodopa?
agonists of dopamine
75
(blank) will dilate the blood vessels in the kidneys.
| Why is this important?
Dopamine
When your body is in shock your blood will go to your brain and your kidney will go into failures so dopamine is necessary
76
Isoproterenol has the highest affinity for what receptors?
all beta receptors
77
What is the therapeutic use of isoproterenol?
bradycardia (heart block, cardiac arrest), bronchospasms
78
What are the cardiovascular responses of isoproterenol (b1 and b2)?
increase in cardiac output due to increased heart rate and contractility (β1)
vasodilation of most vascular beds (β2)
increase in systolic and pulse pressure, decrease in diastolic pressure, slight decrease in MAP
79
What are the other smooth muscle responses of isoproterenol (b2)?
airways – significant dilation
gut – transient decrease in motility
bladder – relaxation of detrusor muscle (promotes filling)
uterus – relaxation
80
Does norepinephrine raise blood pressure or lower it?
raises
81
Does isoproterenol raise or lower blood pressure?
lowers
82
Does epinephrine raise or lower blood pressure?
lowers at low doses, highers at high doese
83
What is the therapeutic use of Dobutamine?
cardiogenic shock, acute heart failure
84
Dobutamine has the highest affinity for what receptors?
B1 then B2
85
What is the mechanism of action for dobutamine?
(+) dobutamine – selective activation of β1 receptors
α1 antagonist
(-) dobutamine – α1 agonist
86
What is the pharmacologic responses of dobutamine?
increased cardiac output (β1) primarily through an increase in contractility
increase in systolic and pulse pressure (little change in diastolic pressure) increase in MAP
87
What is prenalterol?
a selective beta 1 agonist
88
What drug does this describe:
mechanism of action – selective activation of β2 receptors
pharmacologic responses – smooth muscle relaxation, especially airways
therapeutic uses – obstructive airway diseases, acute bronchospasms,preterm labor
terbutaline
89
Metaproterenol, albuterol, ritodrine are all what kind of agonists?
b2 selective agonists
90
What drug does this describe:
mechanism of action – selective activation of α receptors (α1 and α2)
pharmacologic responses – smooth muscle contraction, especially vascular
therapeutic uses – nasal decongestant
oxymetazoline
91
What are these drugs useful for tetrahydrozoline, naphazoline, xylometazoline
imidazolines
92
What drugs does this describe:
mechanism of action – selective activation of α1 receptors
pharmacologic responses – smooth muscle contraction
therapeutic uses – vasopressor, nasal decongestant, mydriatic
phenylephrine
93
Wahat drug does this describe:
mechanism of action – selective activation of α2 receptors
pharmacologic responses – reduced sympathetic tone (central effect), inhibits NE release
therapeutic uses – hypertension, reducing sympathetic responses associated with withdrawal, analgesic adjuvant
clonidine
94
What are these drugs agonists of?
| methyldopa, guanfacine, guanabenz, dexmedetomidine
selective alpha 2 agonists
95
What drug does this describe:
mechanism of action – indirectly acting sympathomimetic; stimulates the release of neurotransmitters (central and peripheral)
```
pharmacologic responses
increased cardiac output
vasoconstriction - increases systolic, diastolic, and mean arterial pressure
contraction of urinary bladder sphincter
CNS stimulation
```
therapeutic uses – narcolepsy, attention deficit hyperactivity disorder (ADHD), appetite suppression, enuresis, incontinence
toxicity
CNS effects - restlessness, dizziness, tremor, irritability, anxiety, delirium, paranoia, hallucinations
cardiovascular effects – severe hypertension,
amphetamine
96
What kind of drugs are these?
| modafinil, dextroamphetamine, methampetamine, benzphetamine, methylphenidate, cocaine, tyramine
other indirectly acting sympathomimetics
97
What drug does this describe:
mechanism of action – mixed acting sympathomimetic: stimulates release of NE, also causes direct activation of α and β receptors
pharmacologic responses – vasoconstriction, positive inotropy, bronchodilation, CNS stimulation
therapeutic uses – bronchodilator, nasal decongestant, mydriatic, narcolepsy
ephedrine
| find in a lot of OTC herbal medications
98
What are these drugs an example of pseudoephedrine, phenylpropanolamine
other mixed acting sympathomimetics –
99
(blank) gets taken up like NE to stay in the synaptic cleft longer as well as cause reverse transport,where endogenous NE release is increased
amphetamine
100
What drug does this describe:
mechanism of action
-blocks catecholamine metabolism by inhibiting monoamine oxidase (MAO)
therapeutic uses
-depression
Parkinson’s disease
pharmacologic responses
-enhance neurotransmission at catecholaminergic synapses
Phenylzine
101
What is entacapont?
a COMT inhibitor
102
tyramine is take up by presynapatic neurons via the norepinephrine transporter (NET). Once inside the cell tyramine is normally metabolised by MAO. If MAO is inhibited by compounds such as phenylzine, the tyramine can then cause the release of endogenous neurotransmitters such as norepinephrine (NE). Because inhibition of MAO also increases the amount of NE available, the result can be a massive release of NE resulting in (blank).
hypertensive crisis
103
What does a-methyltyrosin do?
inhibites tyrosine hydroxylase
104
What does resperine do?
inhibits vesicular monoamine transporter
105
What does guanethidine do?
inhibits norepinephrine
106
What does oxymetazoline do?
a1 and a2 receptor agonist
107
What does phenylephrine do?
a1 receptor agonist
108
What does clonidine do?
a2 receptor agonist
109
What does isoproterenol do?
b1 and b2 receptor agonist
110
What does dobutamine do?
b1 receptor agonist
111
What does terbutaline do?
b2 receptor agonist
112
What does phentolamine do?
a1 and a2 receptor agonist
113
what does prazosin do?
a1 receptor antagonist
114
What does yohimnine do?
a2 receptor antagonist
115
What does propranolol do?
B1 and B2 receptor antagonist
116
What does metoprolol do?
B1 receptor antagonist
117
What does entacapone do?
inhibits catechol-o-methyl transferase
118
What does phenelzine do?
inhibits monoamine oxidase
