Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 825 > ANS-6,7,8 > Flashcards

ANS-6,7,8 Flashcards

1
Q

Monoamines contain one ___ group connected to an aromatic ring by ___ carbon chain

A

amino, 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

examples of monoamines include

A

serotonin, dopamine, norepinephrine, epinephrine, and (histamine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Catecholamines are monoamines with a ___ group

A

catechol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Examples of catecholamines

A

dopamine, norepinephrine, and epinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

BioSynthesis of Catecholamines:
1) tyrosine, 2) ____, 3) Dopamine, 4) ___, 5) epinephrine

A

L-Dopa, Norepinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What step (enzyme) of catecholamine biosynthesis is rate limiting?

A

tyrosine hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is this?

A

L-Tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What inhibits tyrosine hydroxylase?

it’s tyrosine with a methyl on it

A

Metyrosine (Demser)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What inhibits L-Aromatic Amino Acid Decarboxylase?

A

Carbidopa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Norepinephrine Neurotransmission: Step 1 - ___ is transported into the ___ ending or varicosity by a ___ dependent carrier

A

Tyrosine, noradrenergic, sodium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Norepinephrine Neurotransmission: Step 2 - tyrosine is converted to ___ by tyrosine ___ which is converted to ___ by L-dopa ___

A

L-dopa, hydroxylase, dopamine, decarboxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Norepinephrine Neurotransmission: Step 3 - ___ is transported into the vesicle by ___

A

dopamine, vesicular monoamine transporter (VMAT)

*VMAT also transfers NE and other amines into vesicles as well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Norepinephrine Neurotransmission: Step 4 - Dopamine is converted to ___ in the vesicles by ___

A

NE, dopamine-B-hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Norepinephrine Neurotransmission: Step 5 - release of neurotransmitter occurs when an ___ opens voltage-sensitive ___ channels and increases intracellular calcium. Fusion of vesicles with the surface membranes results in expulsion of NE

A

action potential, calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Norepinephrine Neurotransmission: Step 6 - NE binds to ___ receptors on the postsynaptic cell

A

adrenergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Norepinephrine Neurotransmission: Step 7 - NE binds to ___ receptors present on the ___ terminal

A

regulatory, presynaptic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Norepinephrine Neurotransmission: Step 8 - NE diffuses out of the cleft or is re-uptaken into the cytoplasm of the terminal by the ___ where it is metabolized by ___ or transported by ___ back into vesicles

A

NE transporter (NET), Monoamine oxidase (MAO), VMAT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Norepinephrine Neurotransmission: Step 9 - NE can also diffuse away from the synaptic cleft into other cells where it can be degraded by ___

A

catechol-O-methyltransferase (COMT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is this?

A

Dopamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What receptors does epinephrine work on?

A

B1, B2, a1, a2
basically all of them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What receptors does norepinephrine work on?

A

a1, a2, B1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Direct acting adrenergic receptor agonists: Norepinephrine
* Potent ___ and ___ receptor agonist
* substrate for ___ and ___ (metabolized quickly)
* ___ administeration
* Sodium bisulfite used in preparations to prevent ___
* used as a ___

A
  • a1, B1
  • MAO, COMT
  • parenteral
  • oxidation
  • pressor (vasoconstriction)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Direct acting adrenergic receptor agonists: Epinephrine
* Potent ___, ___, and ___ receptor agonist
* Substrate for ___ and ___
* ____ administration
* Sodium bisulfite used in preparations to prevent ___
* available as many salts: hydrochloride, nitrate, and bitartrate
* used for ___ in combination with local anesthetics

A
  • a, B1, B2
  • MAO, COMT
  • parenteral
  • oxidation
  • anaphylaxis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Epinephrine:
Lower [ ] effects at ___ and ___ predominately.
Higher [ ] effects at ___ predominantly

A

Lower: B1 and B2
Higher: a1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Clinical use of epinephrine:
treatment of ____ or ____ ; adjunct with local ____

A

acute anaphylaxis, cardiac arrest, anesthetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Problems with epinephrine: not orally active due to ___ and ___ breakdown in the liver (___ metabolism). Can produce unwanted effects through broad activation of ___ receptors

A

MAO and COMT, first pass, adrenergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Main action of Norepinephrine:
* activates ___ and ___ receptors. Little affinity for ____
* ___ agonist (vasoconstriction leading to a rise in BP)
* ___ agonist (cardiac stimulation by increase in force and conduction)

A
  • activates a and B1 receptors. Little affinity for B2
  • a1
  • B1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Main action of Epinephrine:
* activates __ and __ receptors
* ___ agonist (Vasocontriction leading to a rise in BP)
* ___ agonist (Cardiac stimulation by increasing in force, rate, and conduction)
* ___ agonist (Vasodilation leasing to fall in BP and bronchodilation)

A
  • a and B
  • a1
  • B1
  • B2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Main action of Dopamine:
Lower doses -
* ___ agonist (Vasodilation in renal, messenteric, and coronary arteries increasing blood flow)
* ___ agonist (cardiac stimulation by increasing in force, rate and conduction)

Higher doses -
* ___ agonist (Vasoconstriction leading to a rise in blood pressure)

A
  • D1
  • B1
  • a1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Directly-acting receptor agonists: D1 agonist Dopamine (Intropin) Action-
* Renal D1-receptor agonist, renal vessel ___
* Direct and indirect ___ and ____ agonist (high dose)
* cardiac stimulation and systemic ____ outside the kidney

A
  • Dilation
  • B1 and a1
  • vasoconstrictor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Clinical use for Dopamine (Intropin)

A

shock, acute congestive heart failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

T or F: Dopamine must be given via IV

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is this?

A

Fenoldopam

Selective D1 agonist used for severe hypertension in hospitalized patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Direct acting adrenergic receptor agonists: mixed b1, a1 receptor agonists - Dobutamine (Dobutrex)
* (+)-enantiomer: potent __ receptor agonist
* (-)-enantiomer: potent __ receptor agonist, potency for B receptors reduced (10x)
* racemic exerts a much stronger ___ than chronotropic effect

A
  • B1
  • a1
  • inotropic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

T or F: Dobutamine (Dobutrex) is metabolized by MAO and not sensitive to COMT

A

False; Dobutamine (Dobutrex) is metabolized by COMT and not sensitive to MAO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Direct acting adrenergic receptor agonists: mixed b1, a1 receptor agonists - Dobutamine (Dobutrex)
* ___ half life (2 __)
* Administered via ___
* Used for acute ___, shock, and “stress tests”

A
  • short, minutes
  • IV
  • heart failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Adrenergic Receptor Subtypes-a1(Gq): Agonist uses

A
  • nasal decongestion
  • mydriasis without cycloplegia
  • pressor
  • vasoconstrictor in regional anesthesia (keep drug localized)
  • vascular failure in shock and supraventricular tachycardia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Adrenergic Receptor Subtypes-a1(Gq): Antagonist uses

A
  • hypertension
  • benign prostatic hyperplasia
  • pheochromocytoma

pheochromocytoma - benign tumor that develops in an adrenal gland.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Direct acting adrenergic receptor agonists:
a1 receptors - Examples

A
  • Phenylephrine (Neosynephrine)
  • Methoxamine (Vasoxyl)
  • Oxymetazoline (Visine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is this?

A

Phenylephrine (Neosynephrine)

direct a1 agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Direct a 1 Agonist: Phenylephrine
Administration can be ___, ___, or ___

A

parenteral, oral, or local

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

T or F: Phenylephrine is a substrated for MAO

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Direct a1 receptor agonists:
This is an example of…

A

2-aralkylimidazolines

44
Q

The imidazoline cation is ___ stabilized allowing the +
charge to be spread over the entire three atom system. Thus,
imidazolines are more ___ than simple aliphatic amines.

A

resonance, basic

45
Q

Direct a1 receptor agonists:
* ___ agonists at a receptors
* Administered ____ to promote ____
* ____ nature of imidazoline ring causes compounds to
exist in ____ form at a physiologic pH
* Tachyphylaxis/Desensitization
* Used as nasal and ophthalmic decongestants

A
  • partial
  • topically/locally, vasoconstriction
  • basic, ionized
46
Q

a2 (Gi) receptors are found ___synaptically and function as ___receptors to inhibit ___ output

A

presynaptically, autoreceptors, sympathetic

47
Q

a2 agonists are used for…

A

hypertension, pain, glaucoma

48
Q

Examples of a1 receptor agonists

A

Naphazoline (Privine), Tetrahydrozoline (Visine), Oxymetazoline (Afrin)

49
Q

Direct acting a2 receptor agonist examples

A
  • Clonidine (Catapres)
  • Methyldopa (Aldomet)
  • Guanabenz (Wytensin)
  • Guanfacine (Tenex)
  • Brimonidine
  • Apraclonidine (Iopidine)
  • Tizanidine (Zanaflex)
50
Q

What is this? What kind of receptor recognizes it?

A

Clonidine, a2 agonist

51
Q

a2 agonists ___ blood pressure by reducing ___ output from the brain

A

reduce, sympathetic

52
Q

a2 receptors cause inhibition of NE release (decreases sympathetic tone in the CNS). What effects does decreased sympathetic tone have in the body?

A
  • Decreased HR
  • Decreased contractility
  • Decreased renin release
  • Decreased vasoconstriction
53
Q

Direct acting a2 receptor agonist: Clonidine facts
* (___)imidazolidine
* Selective a2 receptor agonist (also imidazoline receptor)
* activation of a2 receptors in ___ (decrease SNS activity)
* Administration: ___ , ___, and ____
* Uses: Hypertension, opiate withdrawal , neuropathic pain, and ___
* Side effects: hypotension, sedation, ___

A
  • Phenylimino
  • CNS
  • oral, parenteral, transdermal
  • ADHD
  • dry mouth
54
Q

For a2 agonists: the basicity of the guanidine group (pKa = 13.6) is decreased (to pKa = 8.0) because of …

A

the attachment to the dichlorophenyl ring

chlorine is a e- withdrawing group (even distribution)

55
Q

T or F: Drugs like Clonidine can cross into the CNS

A

True

double chlorine is key

56
Q

Problems with Clonidine

A

hypotension, sedation, dry mouth, withdrawal syndrome sometimes seen after prolonged use (hypertension, tachycardia, angina or myocardial infarction)

57
Q

a2 “Open-ring” imidazolidines
examples

A

Guanabenz (Wytensin) and Guanfacine (Tenex)

58
Q

a2 open ring imidazolines:
* Two atom bridge to the guanidine group ___ the pKa so that the drug is mostly ___ at physiological pH
* ___ has the shortest t-1/2 at about ___ . Half-life of clonidine and guanfacine is 12-16 hours
* Administration: ___
* Uses: ___, ADHD (guanfacine)

A
  • decreases, non-ionized
  • Guanabenz, 6 hours
  • oral
  • hypertension
59
Q

a2 receptor agonist: Methyldopa (Aldomet)
* A ___ metabolized to an active
a2 receptor agonist, (1___, 2___)-a-
methylnorepinephrine
* act at ___ a2 receptors to decrease sympathetic outflow
* Administration: ___
* Uses: ___ (especially during pregnancy)

A
  • prodrug, (1R, 2S)
  • CNS
  • oral
  • hypertension
60
Q

a2 receptor agonist: Methyldopate
* Water soluble, ester hydrochloride salt, Methyldopate, is used for
___ solutions

A

parenteral

61
Q

Steps of Methyldopa/Methyldopate prodrug activation:
* Methyldopate (esterases) = ____
* Methyldopa (____) = a-Methyldopamine
* a-Methyldopamine (____) = (1__, 2__)-a-methylnorepinephrine (active compound)

A

Methyldopa
L-aromatic amino acid decarboxylase
Dopamine B-hydroxylase
1R, 2S

62
Q

Direct Acting a2 Agonist: Brimonidine action - Used for ___. Inhibits ___ production (acute effect) and stimulate aqueous humor ___ (chronic effect)

A

glaucoma, aqueous humor, outflow (drainage)

63
Q

Problems with Brimonidine

A

allergic conjunctivitis

64
Q

What is this?

A

Brimonidine

65
Q

B1 receptors are located where? Action?

A

Heart and kidney,
Increases:
* force of contraction
* HR
* conduction velocity in AV node
* renin release

66
Q

B2 receptors are located where? Action?

A

smooth muscle,
* relaxation (bronchial smooth muscle)
* vasodilation

67
Q

B3 receptors are located where? Action?

A

urinary bladder,
* relaxation
* prevention of urination

68
Q

B1 agonists are used for…

A

shock and congestive heart failure

69
Q

B1 antagonist are used for…

A
  • hypertension
  • angina
  • arrhythmias
  • congestive heart failure
70
Q

B2 agonists are used for…

A
  • asthma
  • premature labor
71
Q

B2 antagonists are used for…

A

Glaucoma

72
Q

B3 agonists are used for…

A

overactive bladder

73
Q

Direct acting B receptor agonists - Non-selective example

A

Isoproterenol (Isuprel)

74
Q

Direct acting B receptor agonists - B1-selective examples

A

Dobutamine (Dobutrex)
Dopamine (Intropin) (MOA complex)

75
Q

Direct acting B receptor agonists - B2-selective examples

A
  • Albuterol (Proventil, Ventolin)
  • Salmeterol
  • Ritodrine
  • Terbutaline
  • Metaproterenol
76
Q

Direct acting B receptor agonists - B3-selective examples

A

Mirabegron (Myrbetriq)

77
Q

What is this? What is it selective for?

A

Isoproterenol, non-selective

78
Q

Isoproterenol
* ___selective
* Bronchodilation
* ___ cardiac output
* metabolized by conjugation reaction (Phase II) and by ___
* not sensitive to ___
* administration: ___, ___, and ___ (inhaled)
* uses: asthma, COPD, cardiostimulant

A
  • non
  • increased
  • COMT
  • MAO
  • oral, parenteral, and local
79
Q

Isoproterenol Action - ___ and ___ receptor agonist (non-selective):
* ___ and ___ effects (increasing cardiac output)
* in ___ vessels, stimulation of ___ receptors results in vasodilation and reduced peripheral resistance (may cause BP to ____)

A

B1 and B2
* inotropic and chronotropic
* Peripheral, B2, fall

80
Q

Isoproterenol Clinical Use:
* Emergency use to ___ the HR in patients with ___ or heart block before pacemaker implantation
* Patients with ___ dysfunction & ___ HR with high systemic vascular resistance: after cardiac surgery in patients who previously used ___
* Asthma and COPD

A
  • increase, bradycardia
  • systolic, slow
  • Beta blockers
81
Q

T or F: Isoproterenol is not routinely used: epinephrine and dopamine more common

A

True

82
Q

Cardiovascular effects of sympathomimetics: (picture)

A

memorize image

83
Q

Direct acting selective B2 receptor agonists: Metaproterenol and Terbutaline
* ___ derivatives
* Selective B2 receptor agonist
* bronchodilation
* cardiac effects observes only at ___ doses
* not metabolized by ___ or ___
* Longer duration of action than ___
* Administration: ___, ___, or ___ (inhaled)
* Uses: Asthma, COPD
* Terbutaline used to prevent ___ labor

A
  • Resorcinol
  • high
  • COMT or MAO
  • Isoproterenol
  • oral, parenteral, local
  • premature
84
Q

Direct selective B2 receptor agonists: Albuterol and Salmeterol
* ___ derivatives
* Bronchodilation
* Cardiac effects observed only at ___ doses
* Not metabolized by ___ or ___
* Longer duration of action than ___
* Administration: ___ and ___ (inhaled)
* Uses: Asthma, COPD

A
  • Meta hydroxymethyl
  • high
  • MAO and COMT
  • isoproterenol
  • Oral and local
85
Q

Direct long acting B2 receptor agonists: Salmeterol and Formoterol -
* Bronchodilation
* onset of action is ___ than other drugs. (___10-20 min, ___ <5 min)
* ___ duration of action
* Not metabolized by ___ or ___
* Administration: ___ (metered dose inhaler and powder)
* Uses: ___ term asthma, COPD
* Not recommended for ___ treatment of asthma

A
  • slower
  • Salmeterol, Formoterol
  • longer
  • COMT or MAO
  • inhalation
  • long
  • acute
86
Q

Structure-Activity Relationships (SAR):
T or F: The bulkier the amino group, the less MAO will act on it

A

True

87
Q

Structure-Activity Relationships (SAR):
T or F: Resorcinol (B2) and Meta-Hydroxymethyl (B2) are metabolized by COMT

A

False; Resorcinol (B2) and Meta-Hydroxymethyl (B2) are NOT metabolized by COMT

Catechols (B) and only meta-OH (a1) are metabolized by COMT.

88
Q

Direct-acting B3 receptor agonists: Mirabegron (Myrbetriq) -
Clinical use and problems

A

Clinical use: overactive bladder
Problems: slow onset (8 weeks), Hypertension

89
Q

Indirect -acting Sympathomimetics: examples

A

amphetamine, pseudoephedrine, ephedrine, tyramine

90
Q

How do indirect-acting sympathomimetics work?

A

Promote release of NE via reverse
action of plasma membrane
transporter

91
Q

What is this?

A

Amphetamine

Notice that there is not a catechol or B-hydroxy

92
Q

Unlike NE and Epi, ephedrine and amphetamine are orally active. This is because ephedrine and amphetamine are not ___

A

catechols

93
Q

Amphetamine and Methamphetamine Overdose Treatment: Weak Bases
* ___ urine to increase excretion– no longer commonly used
* Sedative for ___ symptoms
* Sodium nitroprusside or alpha adrenergic ___ for severe __

A
  • acidify
  • CNS
  • antagonist, hypertension
94
Q

Phentermine/Topiramate (Qsymia): approved for ___ -
* Phentermine: ___ sympathomimetic
* Topiramate: ___ (block sodium channels and glutamate receptors, enhances
___ activity)

A

weight loss
* Indirect
* antiepileptic, GABA

95
Q

Phentermine/Topiramate (Qsymia) should be avoided if the patient has any of these conditions

A
  • hypertension
  • coronary heart disease
  • Pregnant
96
Q

Direct vs Indirect Sympathomimetics:
D-(-)-Ephedrine vs. L-(+)-Pseudoephedrine -
* D-(-)-Ephedrine has desired (__)-configuration at B-OH and (S)-
configuration at the a carbon, so
has **direct **alpha and beta agonist activity
* L-(+)-Pseudoephedrine is the
(S,S)-diastereoisomer; (S)-configuration of B-OH reduces
agonist activity. Major mechanism is via ___

A
  • R
    *reversal of the transporter
97
Q

Problems with ephedrine and pseudoephedrine

A
  • Increased blood pressure
  • increased heart rate via enhanced NE signaling from SNS
98
Q

T or F: it is safe to take pseudoephedrine with an MAO inhibitor

A

False; contraindicated

99
Q

wine and cheese effect :(

A
  • Tyramine is an indirect sympathomimetic agent and can produce strong effects if it
    reaches sympathetic nerve terminals.
  • Normally, almost all ingested tyramine is rapidly broken down by MAO in the liver.
  • MAO inhibitors decrease the breakdown of tyramine resulting in a bolus release of NE, potentially resulting in a hypertensive crisis
100
Q

Norepinephrine Transporter (NET) Inhibitors: Cocaine’s Action
* block NET
* ___ uptake
* Enhance __ signaling by keeping more transmitter in the synaptic cleft

A
  • decrease
  • NE
101
Q

Cocaine: Clinical use

A

Local anesthetic (sodium channel blocker) for nasal mucosa and vasoconstriction

102
Q

Side effects of cocaine:

A

Peripheral
* Increased blood pressure and heart rate
* Potential for stroke, cardiac arrhythmias, myocardial infarction and sudden death

103
Q

Methylphenidate action:
* Blocks ___ and ___ reuptake transporters that transport ___ from synaptic cleft
back to presynaptic terminal
* Overall effect: enhance NE and DA signaling

A
  • NE and DA
  • monoamines
104
Q

Methylphenidate Clinical use:

A
  • ADHD, narcolepsy (similar to amphetamine)
  • Recommended for preschool children with ADHD
105
Q

Methylphenidate problems

A
  • (similar to amphetamine)
  • Priapism (prolonged penile erection): rare but serious
  • Also addictive potential (C-II drug) via enhanced DA signaling
106
Q

What is this?

A

Methylphenidate

107
Q

NET Inhibitor: Atomoxetine action -
* Selective inhibitor of NET and thus enhances NE levels.
* used for Attention deficit hyperactivity disorder (ADHD)
* Not controlled substance – low potential for addiction
* Non-stimulant: isn’t associated with agitation or sleeplessness

BUT…

A
  • suicidal ideation
  • Priapism (prolonged penile erection): rare but serious
  • May take longer than stimulants for effect
  • may be less effective

bonk

PHRM 825 (49 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions