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Block 1 Week 7 > ANS Harvey Part 3 > Flashcards

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

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2
Q

are exogenous compounds that imitate the functional responses produced by endogenous catecholamines

A

sympathomimetics

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3
Q

are exogenous compounds that block the functional responses to endogenous catecholamines or sympathomimetics.

A

sympatholytics

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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

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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

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6
Q

Where are alpha adrenergic receptors found?

A 
location – smooth muscle 
blood vessels
eye (iris radial muscle)
bladder (sphincter muscle)
skin (piloerector muscles)
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7
Q

What is the signaling mechanism of alpha 1 adrenergic receptors?

A

Gq activation of phospholipase C

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8
Q

What is the the response of activated alpha 1 adrenergic receptors?

A

contraction

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9
Q

Summarize Alpha I adrenergic receptors

A

Gq-> IP3-> Ca2+-> smooth muscle contraction

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10
Q

alpha adrenergic α2 receptors are located where?

A

some vascular smooth muscle

central and peripheral presynaptic nerve terminals

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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

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12
Q

What is the response of alpha adrenergic α2 receptors?

A

vasoconstriction

inhibition of neurotransmitter release

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13
Q

How does alpha adrenergic α2 receptors create vasoconstriction?

A

It inhibits cAMP (cAMP inhibits contractions) via inhibition of adenylul cyclase

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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.

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15
Q

Where do you find beta adrenergic β1 receptors?

A

heart
kidney
adipose tissue

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16
Q

What is the signaling mechanism of beta adrenergic β1 receptors?

A

– Gs activation of adenylyl cyclase

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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

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18
Q

What is positive chronotropic effect?

A

increase firing rate of heart

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19
Q

What is positive dromotropic effect?

A

increase conduction velocity

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20
Q

What is positive inotropic effect?

A

increase contractility

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21
Q

What is positive lusitropic effect?

A

Increase rate of relaxation

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22
Q

release of (blank)leads to an increase in angiotensin II production

A

renin

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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
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24
Q

What is the signaling mechanism of beta adrenergic β2 receptors?

A

Gs activation of adenylyl cyclase

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25
Q

What is the response of beta adrenergic β1 receptors?

A

increase heart rate and contractility
relax smooth muscle
increase glycogenolysis

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26
Q

β2-receptor activation stimulates (blank)

A

glycogenolysis

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27
Q

beta adrenergic β3 receptors

location – ?

signaling mechanism – ?
response – ?

A

adipose tissue
Gs activation of adenylyl cyclase
lipolysis

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28
Q

What are juxtaglomeular cells?

A

receive sensory information of sympathetic system which makes them release renin

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29
Q

dopaminergic D1-5 receptors
Location–?
Signaling pathway–?
Response—?

A

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

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30
Q

D1-5 receptors in the vascular smooth muscle (kidney) utilizes D1 & D5 to activated Adenylyl cyclase with what G protein?

A

Gs

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31
Q

D2-4 receptors in theCNS utilizes D2-D4 to activated Adenylyl cyclase with what G protein?

A

Gi

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32
Q

It is important to recognize that it is not uncommon to actually find (blank) adrenergic receptors in any given cell type.

A

more than one type of

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33
Q

All the receptors discussed so far may also be involved in regulating (blank) not discussed here.

A

other signaling pathways

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34
Q

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

A

subclassifications

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35
Q

catecholamines consist of 2 moieties?

A

catachol and an ethylamine side chain

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36
Q

What has a benzene ring with hydroxyls at the 3 (meta) and 4 (para) positions?

A

catechol

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37
Q

The α and β carbons of the ethylamine moiety of catecholamines are (blank) carbons.

A

chiral

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38
Q

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)

A

stereoisomers
diastereomers

l-isomer.

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39
Q

(sympathomimetics) Compounds that mimic the responses produced by sympathetic stimulation can be divided into three different categories; what are they?

A

direct, indirect, mixed

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40
Q

(blank) produce their effects by directly activating adrenergic receptors. Endogenous catecholamines belong to this class.

A

Direct acting compounds

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41
Q

(blank) produce their effects by increasing the availability of endogenous catecholamines. This can be achieved by:

inhibiting reuptake
stimulating release
inhibiting metabolism

A

Indirect acting compounds

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42
Q

(blank) compounds produce their effects by both direct and indirect mechanisms.

A

Mixed

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43
Q

Direct acting sympathomimetics will have substitutions on at least 2 of the following 3 positions: What are they?

A

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.

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44
Q

With direct acting compounds for sympathomimetics:large substitutions on the terminal nitrogen tend to promote (blank)
small substitutions tend to promote (blank)

A

β adrenergic receptor activity

α adrenergic receptor activity.

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45
Q

Hyroxyl substitutions on the 3 and 5 positions of the benzene ring tend to enhance (blank)

A

β2 adrenergic receptor selectivity.

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46
Q

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.

A

none or only 1 substitution

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47
Q

(SYMPATHICMIMETICS WITH INDIRECT ACTIVITY) For sympathomimetics with (blank), both d- and l- isomers may be active. For example:
ex )Amphetamine, Ephedrine

A

α carbon substitutions

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48
Q

(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).

A

β carbon

49
Q

(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.

A

hydroxyls

50
Q

(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)

A

α carbon

51
Q 
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
A

α agonists

alpha 1 and 2 receptors

52
Q

What is an important sympathomimetic with indirect activity?

A

amphetamine

53
Q

What are the order of affinity for agonist for Alpha 1 receptor?

A

Epi ≥ NE&raquo_space; Iso

phenylephrine

54
Q

What are the order of affinity for agonist for Alpha 2 receptor?

A

Epi ≥ NE&raquo_space; Iso

clonidine

55
Q

What are the order of affinity for agonist for Beta1 receptor?

A

Iso > Epi = NE

dobutamine

56
Q

What are the order of affinity for agonist for Beta 2 receptor?

A

Iso > Epi&raquo_space; NE

terbutaline

57
Q

What are the order of affinity for agonist for Beta 3 receptor?

A

Iso = NE > Epi

58
Q

When would you use aympathomimetics?

A 
Cardiovascular applications (acute hypertension), respiratory system applications (asthma), anaphylaxis
Opthalmic applications (glaucoma)
Genitourinary Applications (preterm labor)
CNS (muscle relaxation)
59
Q 
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

A

sympathomimetics

60
Q 
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
A

Sympathomimetics

61
Q

What is a therapeutic use of norepinephrine?

A

hypotension (shock)

62
Q

What receptor does noreinephrine have the most affinity for?

A

α1≥α2; β1»β2

63
Q

What are the cardiovascular responses of norepinephrine (a1 and b2)?

A

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
Q

What are the other smooth muscle responses of norepinephrine (a1)

A

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
Q

What receptor does epinephrine have the most affinity for?

A

α1=α2; β1=β2

66
Q

At low doses of epinephrine which receptor is predominantly activated?
At high doses of epinephrine which receptor is predominantly activated?

A

beta 2

alpha 1

67
Q

What is a therapeutic use of epinephrine?

A

bronchospasms, anaphylactic shock, cardiac arrest, open angle glaucoma, local anesthetic (adjunct)

68
Q

What are the cardiovascular responses of epinephrine (b1 and b2)?

A

low doses – similar to isoproterenol (β1 and β2)

high doses – similar to norepinephrine (α1 and β1)

69
Q

What are the other smooth muscle responses of epinephrine (a1 and b2)?

A

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
Q

What receptors does dopamine have the most affinity for?

A

D1-5>β>α

71
Q

What are the therapeutic uses of dopamine?

A

cadiogenic shock, heart failure

72
Q

What are the cardiovascular responses of dopamin (D1/5, B1 and a1 effects)?

A

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
Q

What are the central effects of dopamine

A

involved in controlling motor movement in the basal ganglia

inhibits prolactin secretion in the anterior pituitary

74
Q

What are these fenoldopam, bromocriptine, levodopa?

A

agonists of dopamine

75
Q

(blank) will dilate the blood vessels in the kidneys.

Why is this important?

A

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
Q

Isoproterenol has the highest affinity for what receptors?

A

all beta receptors

77
Q

What is the therapeutic use of isoproterenol?

A

bradycardia (heart block, cardiac arrest), bronchospasms

78
Q

What are the cardiovascular responses of isoproterenol (b1 and b2)?

A

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
Q

What are the other smooth muscle responses of isoproterenol (b2)?

A

airways – significant dilation
gut – transient decrease in motility
bladder – relaxation of detrusor muscle (promotes filling)
uterus – relaxation

80
Q

Does norepinephrine raise blood pressure or lower it?

A

raises

81
Q

Does isoproterenol raise or lower blood pressure?

A

lowers

82
Q

Does epinephrine raise or lower blood pressure?

A

lowers at low doses, highers at high doese

83
Q

What is the therapeutic use of Dobutamine?

A

cardiogenic shock, acute heart failure

84
Q

Dobutamine has the highest affinity for what receptors?

A

B1 then B2

85
Q

What is the mechanism of action for dobutamine?

A

(+) dobutamine – selective activation of β1 receptors
α1 antagonist
(-) dobutamine – α1 agonist

86
Q

What is the pharmacologic responses of dobutamine?

A

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
Q

What is prenalterol?

A

a selective beta 1 agonist

88
Q

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

A

terbutaline

89
Q

Metaproterenol, albuterol, ritodrine are all what kind of agonists?

A

b2 selective agonists

90
Q

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

A

oxymetazoline

91
Q

What are these drugs useful for tetrahydrozoline, naphazoline, xylometazoline

A

imidazolines

92
Q

What drugs does this describe:
mechanism of action – selective activation of α1 receptors

pharmacologic responses – smooth muscle contraction

therapeutic uses – vasopressor, nasal decongestant, mydriatic

A

phenylephrine

93
Q

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

A

clonidine

94
Q

What are these drugs agonists of?

methyldopa, guanfacine, guanabenz, dexmedetomidine

A

selective alpha 2 agonists

95
Q

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,

A

amphetamine

96
Q

What kind of drugs are these?

modafinil, dextroamphetamine, methampetamine, benzphetamine, methylphenidate, cocaine, tyramine

A

other indirectly acting sympathomimetics

97
Q

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

A

ephedrine

find in a lot of OTC herbal medications

98
Q

What are these drugs an example of pseudoephedrine, phenylpropanolamine

A

other mixed acting sympathomimetics –

99
Q

(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

A

amphetamine

100
Q

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

A

Phenylzine

101
Q

What is entacapont?

A

a COMT inhibitor

102
Q

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).

A

hypertensive crisis

103
Q

What does a-methyltyrosin do?

A

inhibites tyrosine hydroxylase

104
Q

What does resperine do?

A

inhibits vesicular monoamine transporter

105
Q

What does guanethidine do?

A

inhibits norepinephrine

106
Q

What does oxymetazoline do?

A

a1 and a2 receptor agonist

107
Q

What does phenylephrine do?

A

a1 receptor agonist

108
Q

What does clonidine do?

A

a2 receptor agonist

109
Q

What does isoproterenol do?

A

b1 and b2 receptor agonist

110
Q

What does dobutamine do?

A

b1 receptor agonist

111
Q

What does terbutaline do?

A

b2 receptor agonist

112
Q

What does phentolamine do?

A

a1 and a2 receptor agonist

113
Q

what does prazosin do?

A

a1 receptor antagonist

114
Q

What does yohimnine do?

A

a2 receptor antagonist

115
Q

What does propranolol do?

A

B1 and B2 receptor antagonist

116
Q

What does metoprolol do?

A

B1 receptor antagonist

117
Q

What does entacapone do?

A

inhibits catechol-o-methyl transferase

118
Q

What does phenelzine do?

A

inhibits monoamine oxidase

Block 1 Week 7 (10 decks)

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