Phcol 402 Quiz #2
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1.
identify
:
identify
:
norepinephrine
2.
epinephrine
identify
6.
:
a = tyrosine
b = dopa
c = dopamine
d = norepi
e = epinephrine
identify
3.
7.
NE is released into the synaptic cleft by ___________. NE
interacts with receptors on the postsynaptic membrane to
cause either _________ or __________ of the membrane of the
effector organs. The signal is terminated by re-uptake of
the transmitter into the nerve terminal.: Ca2+-dependent
exocytosis, hyperpolarizations (IPSP) or depolarizations
(EPSP)
8.
When the adrenergic nerves come in to innervate the
smooth muscle, they ramify at the __________________. The
adventitia contains a lot of connective tissue. They form the
terminal effector plexus in the outermost muscle layer.
These varicosities are the sites where ___ is released on the
outer layer of the vascular smooth muscle.: adventitia-medial
junction
:
dopamine
identify
4.
:
isoproterenol
NE
9.
NE is released only on the _____ surface of the media and the
only way smooth muscle cells in deeper layers are
activated is by - what two ways?: outer
diffusion of NE down to those cells, or because the smooth
muscle cells in the inner layers are all electrically coupled
5.
identify
a = tyrosine hydroxylase
b = L-aromatic AA decarboxylase
c = dopamine-beta-hydroxylase
d = phenethaloamine-N-methyltransferase
:
10.
The immediate precursor for the biosynthesis of ___________ is
the amino acid, tyrosine.: catecholamines
11.
The immediate precursor for the biosynthesis of
catecholamines is the amino acid, _____________: tyrosine.
12.
Tyrosine is made from ______ by the enzyme _______________.:
phenylalanine,
phenylalanine hydroxylase
13.
Tyrosine is converted in the cytoplasm to ____ by tyrosine
hydroxylase.: DOPA
23.
NE can also be metabolized by____________________, which is
extra-neuronal,: catecholamine-O- methyl transferase (COMT)
14.
DOPA is converted to _____ in the cytoplasm by dopadecarboxylse. The enzyme is also known as _________.
24.
catecholamine-O- methyl transferase (COMT)
where is this found?: kidney, liver
where does this occur?: dopamine
aromatic-L-amino acid decarboxylase
All of this happens in the cytoplasm of the nerve terminal.
15.
Inside the vesicles dopamine is converted to __ by
dopamine-beta-hydroxylase.
identify
25.
: MAO
where does this occur?: NE
This is what happens in sympathetic nerves.
16.
NE is methylated by _________________________ in the cytoplasm
to produce epinephrine.: phenylethanolamine-N-methy
transferase
17.
In humans the adrenal medulla contains about___% E and ___%
NE.: 80, 20
18.
It is important to know that the ratelimiting step for the
synthesis of E and NE is _____________, a step early in the
synthetic pathway.: tyrosine hydroxylase
19.
Epinephrine and norepinephrine are released by
________________, but adrenergic and cholinergic synapses
differ significantly in the pathways for termination of
synaptic transmission.: Ca2+-dependent exocytosis
20.
How is termination of NE different from Ach?: The main
pathway for termination of NE action is not by destruction of
NE, but by reuptake back into the cytoplasm and ultimately
into the granules or vesicle
At cholinergic synapses the main pathway for termination is
hydrolysis of acetylcholine by acetylcholine esterase. The
choline is then transported back into the presynaptic terminal
by a specific transport system. Acetylcholine, itself is not
transported back into the terminal.
21.
secondary mechanisms by which NE is metabolized: Name 2:
a. Monoamine oxidase (MAO) in the mitochondria. The nerve
terminal has a lot of
mitochondria and MAO.
b. NE can also be metabolized by catecholamine-O- methyl
transferase (COMT), which is extra-neuronal, e.g. found in liver
and kidney
22.
Monoamine oxidase (MAO) in the _______. The nerve terminal
has a lot of __________(same blank) and MAO. Function?:
mitochondria
secondary metabolism of NE
26.
Catecholamine-O-methyl transferase, transfers a methyl
group onto one of the _______ of the aromatic ring.: hydroxyls
27.
T/F the products of MAO and COMT reactions typically do
not associate with each other: FALSE =
The metabolism of catecholamines can be quite complex and
the products of monoamine oxidase can be acted on by
Catecholamine-O-methyl transferase. The products of
Catecholamine-O-methyl transferase can be acted on by
monoamine oxidase.
28.
Identify the substrate and enzyme
: epinephrine & COMT
29.
1. The rate-limiting step in the synthesis of catecholamines is
tyrosine hydroxylase. This is inhibited by _____________. . This
inhibits the___________ pathway.
3.
Since this transporter is the main mechanism for the
termination of the actions of the catecholamines, you would
expect that blocking this transporter would increase the
actions of endogenously released NE. These types of drugs
augment adrenergic transmission.
The adrenal medulla does not have the uptake system that
transports catecholamines in the synapse back into the
nerve terminal.... so cocaine and tricyclic antidepressants
do not affect the adrenal medulla.: alpha-methyl tyrosine,
sympathetic
30.
The action potential-stimulated release of ___ is blocked by
bretylium and guanethidine.: NE
31.
There are also drugs, NAME 2, that block the transporter on
the nerve terminal.: cocaine and tricyclic antidepressants
32.
T/F cocaine and tricyclic antidepressants do not affect the
adrenal medulla.: T = The adrenal medulla does not have the
uptake system that transports catecholamines in the synapse
back into the nerve terminal....
33.
The two transporters types of catecholamines, name them:
one which transports catecholamines into the nerve terminal
one that transports them into the vesicle are completely
different proteins.
They are preferentially acted on by different types of drugs.
34.
There are drugs, eg _________, which block the transport of
catecholamines into the vesicles.
You need to get DA back into the vesicle to make NE.:
reserpine
35.
name the drugs that are associated with affecting
adrenergic transmission
: a = alpha-methyl tyrosine
b = reserpine
c = amphetamines
d = bretylium, guanethidine
e = cocaine, TCAs
36.
Drugs such as reserpine which inhibit the _______________ cause
depletion of catecholamines and interfere with adrenergic
transmission.: transport into the vesicle
37.
5. One class of drugs promotes the release of
catecholamines from the nerve terminal, leading to a
____________ effects. This includes _________ and tyramine will
cause release of catecholamines from the terminal.:
sympathomimetic, amphetamine
38.
__________ displaces catecholamines from storage sites and
blocks adrenergic transmission.: Guanethidine
39.
Inhibition of MAO by the drug ________can cause accumulation
of NE.: pargyline (Eutonyl)
40.
pargyline inhibts what? what does this cause?: MOA,
accumulation of NE
41.
_______ is due to degeneration of the nigrostriatal pathway
with a reduction in dopamine, serotonin, and NE.: Parkinson's
disease
42.
Parkinsons causes a decresae in which 3 Neurotransmitters?:
dopamine, serotonin, and N E.
43.
parkinsons Treatment is to increase dopamine levels using
its precursor DOPA. DOPA is usually supplemented with an
inhibitor of _________________.: peripheral DOPA decarboxylase
44.
Carbidopa inhibits???: dopamine decarboxylase
45.
It is used in combo treatment of Parkinson's Disease with
DOPA because ____ doesn't enter the CNS. When you give a
patient DOPA, a lot of that DOPA is taken up and
metabolized peripherally in sympathetic neurons. By giving
______(same blank), it increases the effective dose of DOPA
for the CNS.: carbidopa
46.
What is purpose of carbidopa?: When you give a patient
DOPA, a lot of that dopa is taken up and metabolized
peripherally
in sympathetic neurons. By giving carbidopa, it increases the
effective dose of dopa for the!
CNS.
62.
Alpha -1 adrenergic receptors are coupled to ___ increases.:
Ca2+
63.
The____ receptor: are located presynaptically on adrenergic
terminal and act to modulate the release of NT, they are
coupled to inhibition of adenylyl cyclases through Gi.
Presynaptic cAMP normally increases NT release.: alpha-2
47.
_______ can be inhibited by tolcapone (tol-capone) , a drug
which is given with carbidopa to Parkinson's patients: COMT
64.
The ____ receptor: mediates contraction of vascular smooth
muscle.: alpha-1
48.
COMT can be inhibited by ________ , a drug which is given with
carbidopa to _______ patients: tolcapone (tol-capone)
65.
_____ receptors: present in the heart and mediates cardiac
stimulation.: Beta-1
66.
_____ receptors: are present in smooth muscle and mediate
relaxation of smooth muscle.: Beta-2
67.
Both ____ & ____ (receptors) are coupled to stimulation of
adenylyl cyclase through Gs.: Beta-1 and Beta-2
68.
______ stimulation normally causes contraction of the
vasculature.: Sympathetic
69.
T/F Sympathetic stimulation of vasculature to skeletal
muscle can
cause either vasodilation or vasoconstriction.: T
70.
• Skeletal muscle vascular smooth muscle:
____ receptors which will cause contraction of the VSM
_____ receptors which can cause relaxation of VSM.: alpha-1
71.
______ receptors are expressed in in fat cells, so it was
assumed thought that they mediated catecholamine
stimulation of __________: Beta-3, lipolysis
72.
In humans Beta-3 it is only present in ____ fat, the type of fat
that plays a role in _______ during hibernation.!: brown,
thermogenesis
73.
Thermogenesis is important for _____ in maintaining body
temperature. !: new borns
74.
In humans the main subtype in fat is actually _____ receptors,
not beta-3: beta-1
Parkinson's
49.
some adrenergic terminals contain presynaptic receptors,
WHAT TWO TYPES?, that modulate adrenergic transmitter
release.: (e.g. muscarinic or alpha-adrenergic receptors)
50.
muscarinic or alpha-adrenergic receptors Normally these
presynaptic receptors are coupled to ________ of NE release.
They function as a feedback inhibitory system. These
presynaptic receptors have a different set of
pharmacologies than most postsynaptic receptors.: inhibition
51.
Presynaptic receptors are often coupled to Gi and inhibition
of ________. Presynaptic ____ normally enhances NT release.:
adenylyl cyclase, cAMP
52.
E > NE >> Iso
receptor type?: alpha
53.
rank the effectiveness of NT to bind to alpha receptors: E >
NE >> Iso
54.
Iso > E> NE
receptor type?: Beta:
55.
rank the effectiveness of NT to bind to beta receptors: Iso >
E> NE
56.
Receptors antagonized by phentolamine or
phenoxybenzamine are
considered ______ receptors.: alpha-adrenergic
57.
Those blocked by propranolol are _____ receptors.: betaadrenergic
58.
phentolamine, antagonizes what receptor?: alpha
59.
phenoxybenzamine antagonizes what receptor?: alpha
60.
___________ is more potent than NE in stimulation of the heart
beating rate. Pharmacologically this indicates that the
effect on heart rate is mediated primarily through ____________
receptors.: isoproterenol (isoprenaline)
beta-2
beta-adrenergic
61.
alpha-2 receptor inhibits what?: they are coupled to inhibition
of adenylyl cyclases through Gi
75.
indicate the receptor type
alpha-1, beta-2, beta-1
:
81.
rats that were treated with thyroid hormones for several
weeks, when you measure the number of adrenergic
receptors in their hearts using a radioactive ligand that
binds relatively specific to beta-receptors
(dihydroalprenolol), you get very significant _____ in the
number of beta-receptors.
this leads to?: increase
76.
indicate location/function
A = contraction of arterial strips
:
This increases sensitivity of the heart to catecholamines and
lead to tachycardia.
82.
__: Beta-2 > Alpha-1 !: Epi
83.
____ receptors over the _____ in VSM leading to vasodilation
and net result is decrease in peripheral resistance: Beta-2,
alpha-1
84.
alpha-1:
alpha-2:
beta-1:
beta-2:
B = relaxation of bronchial smooth muscle
C= heart muscle contraction.
identify catetcholamines
77.
basic function?: mediate contraction of smooth muscle!
:
A to C
presynaptic receptors on adrenergic nerve terminals
thatmodulate NE release !
E > NE >> Iso
They are the predominant adrenergic receptors in heart!
mediate relaxation of smooth muscle
identify catetcholamines
78.
: A to C
85.
Baroreceptors (stretch receptors) in the ____ & _____ (2
locations) send fibers to the CNS, to regulate
activity of the ANS:: carotid sinus
and aortic arch
86.
______ in the carotid sinus
and aortic arch send fibers to the CNS, to regulate
activity of the ANS:: Baroreceptors (stretch receptors)
I > E >> NE
identify catetcholamines
79.
:
A to C
I > E/NE
80.
____ not very effective with beta-two receptors. For practical
purposes we can assume that ___, while active at alpha-1 and
beta-1 receptors is ineffective at beta-2 receptors.
SAME BLANK: NE
87.
indicate the catecholamine
a = NE
b=E
c = isoproterenol
d = Dopamine
:
88.
NE you would expect it to activate the alpha-1 receptors
and increase peripheral resistance, vasoconstriction a lot.
You would also expect NE to activate beat-1 receptors in
the heart. But there will be a _______ to the increase in
peripheral resistance, the blood pressure is going up to high
and this reflex increases _______ activity and lowers HR.:
baroreceptor reflex, parasympathetic
89.
NE will active ___ to increase BP
NE will active ____ to increase HR: alpha-1
beta-1
90.
what is the OVERALL net effect of NE?: you might expect NE
to increase HR by virtue of beta-1 receptors, you actually see a
decrease in heart rate due to the over-whelming influence of
the parasympathetic reflex through baroreceptors.
99.
correlation between the ____ in BP and ____ in heart rate.:
increase, decrease
100.
This relationship between BP and HR is often used as an
index of ________________________: autonomic reflex sensitivity
101.
phenylephrine effect on
BP
sympathetic activity
parasym activity (vagus)
HR: increase
decrease
increase
decrease
The net effect for NE is a slight increase in BP.
91.
102.
T/F The net effect for NE is a slight increase in BP as well as
HR: FALSEEEEE = The net effect for NE is a slight increase in
BP, but you actually see a decrease in heart rate due to the
over-whelming influence of the parasympathetic reflex through
baroreceptors.
92.
Isoproterenol activates which 2 receptors?: beta-1 and beta-2
93.
Isoproterenol overall effect on HR and BP?: activates beta-1
and beta-2, but not alpha-receptors. This will lead to a
relaxation of VSM, vasodilation and a decrease in peripheral
resistance and a decrease in diastolic BP. It will activate beta-1
receptors in heart increasing the rate and force of heart
contractions and increase systolic pressure. The net effect is
that the mean BP falls somewhat.
BP
sympathetic activity
parasym activity (vagus)
HR: decrease
increase
decrease
increase
103.
OVERALL = DECREASE BP, INCREASE HR
94.
95.
The dopamine receptors are relevant to our analysis of
cardiovascular effects because there are D1 receptors in
the _____ & ______ vessels.: renal and mesenteric
96.
These___ receptors mediate vasodilation of VSM in renal and
mesenteric vessels through stimulation of adenylyl cyclase
activity: D1
97.
DOPAMINE effect on BP?: small decrease in peripheral
resistance and it causes an increase in heart rate through beta-1
receptors in heart causing an increase in systolic pressure, so
with DA you get a net increase in BP.
98.
dopamine = small decrease in peripheral resistance and it
causes an increase in heart rate through _____ receptors in
heart causing an increase in systolic pressure, so with DA
you get a net increase in BP.: beta-1
Albuterol
Ritodrine
Tertbutaline
Salmeterol
these are all selective for what receptors? effect?: Beta-2
Selective Adrenergic Agonists
DA has a complicated pharmacology. It can act at receptors
____ and at ______ receptors. And at much higher doses it can
act at _____-adrenergic receptors.: dopamine, beta-1
alpha
histamine effect on
bronchodilation
104.
which is more selective, which would be a better respiratory
drug?
:B
105.
When you have broncho______, you increase FEV: dilation
106.
which is longer acting?
albuterol vs salmeterol?: salmeterol
107.
_____ agonists are used as bronchodilators.: beta-2
118.
____ activates D-1 receptors and increases cAMP levels,
cAMP increases cause vaso___________: Fenoldopam,
vasodilation
119.
There are __ receptors in the mesenteric and renal blood
vessels: D1
108.
120.
Fenoldopam is used for short treatment of ______________ By
promoting vasodilation in renal and mesenteric blood
vessels: hypertension during trauma
121.
Lowering of BP by _____(increase/decreas) Doses of
Fenoldopam: Increasing
122.
____________ receptors in vascular smooth muscle cause
relaxation of vascular smooth muscle coupling to adenylyl
cyclase. Why does cAMP cause relaxation of smooth
muscle?: beta-2 adrenergic
123.
cAMP activates PKA which in turn inhibits the activity of
_____. Calcium stimulation of ____ stimulates contraction of
vascular smooth muscle.
identify which is Isoproterenol and which is salmeterol
: A = Isoproterenol
B = salmeterol
109.
110.
111.
______ (class/receptor) such as ritodrine are also used to
delay labor because they cause relaxation of smooth
muscle.: Beta-2 agonists
A significant number of women who are given ritodrine
to delay labor also show some cardiovascular effects, why?:
v Ritodrine is not absolutely specific for beta-2 receptors !
v Ritodrine effects on heart rate are due to some activity!
of ritodrine with beta-1 receptors
SAME BLANK: myosin light chain kinase (MLCK)
124.
______receptors and several other receptors are coupled to
increases in intracellular free calcium in vascular smooth
muscle by coupling to phospholipase C, liberation of IP3
and mobilization of free calcium. This increase in free
calcium stimulates muscle contraction by stimulating PKC
and MLCK.: Alpha-1 adrenergic
125.
Alpha-1 adrenergic receptors and several other receptors
are coupled to increases in intracellular free calcium in
vascular smooth muscle by coupling to _____, liberation of ___
and mobilization of free calcium. This increase in free
calcium stimulates muscle contraction by stimulating what
two things?: phospholipase C, IP3
126.
cAMP_____ PKA which in turn _______ the activity of myosin
light chain kinase (MLCK).: activates, inhibits
actually a mixture of optic isomers, one acts as an alpha-1
receptor agonist, the other isomer as an alpha-1 receptor
antagonist, both are beta-1 agonists. It is relatively
selective for beta-1 receptors over beta-2 receptors.
DRUG?: Dobutamine
112.
• Dobutamine is a mixture of isomers
• One isomer is an??
• One isomer is an ??
• Both isomers are active against ____: alpha-1 antagonist,
alpha-1 agonist, beta-1
113.
• Used to increase contractile force of heart with lesser
effects on rate and has multiple isomers, agent?:
Dobutamine
114.
In heart most of the the beta-receptors in the ventricle are
_____ receptors. !: beta-1
115.
The S-A node, contain a significant fraction of beta-2
receptors. You preferentially activate beta-1 receptors in
the ventricles and get more of an effect on ___ rather than
____: force, rate
116.
Since ______ works selectively on beta-1 receptors, you do
not get the vasodilation that you would get with IP.
Consequently, there is less reflex increase in sympathetic
activity and less tachycardia: dobutamine
117.
Fenoldopam is a ____ Receptor Agonist: D-1
PKC and MLCK.
: a = Gs
b = Gi
c = cAMP
d = PKA
e = MLCK
129.
130.
NE it is working directly on alpha-1 receptors to cause
vasoconstriction, in the case of tyramine, it acts on the
______ to release NE which in turn acts on alpha-1 receptors
to cause vasoconstriction.: nerve terminal
135.
Foods With High Levels of Tyramine (12): • Cheese
• Pickled herring
• Canned figs
• Chocolate
• Yeasts
• Yogurt
• Game
• Red wine
• Chicken livers
• Fava beans
• Beer
• Meat extracts
136.
amphetamine stimulates which receptors? effect on
BP/HR?: Can stimulate both alpha and beta-adrenergic
receptors. !
identify the enzyme/chemical
127.
128.
134.
major adenylyl cyclase in vascular smooth muscle is ___, a
calcium-inhibited adenylyl cyclase. This makes regulatory
sense because calcium and cAMP have
_________(agonistic/antagonistic) effects on vascular smooth
muscle contraction.: AC3, antagonistic
AC3 is a calcium inhibited adenylyl cyclase. It explains why
low epinephrine cause vasodilation ( Beta-2) and higher
concentrations cause vasoconstriction, why?: (Alpha-1 and
calcium inhibits AC3).
low epinephrine cause vaso_____ and higher concentrations
cause vaso_____: dilation, constriction
! ! 1. Blood pressure increase!
! 2. Heart Rate decreases!
137.
_____ is used as a precursor for the chemical synthesis of
methamphetamine: Pseudoephedrine
138.
causes a longer-lasting pressor response, E or ephedrine?:
ephedrine
139.
Pseudophedrine or pseudophed is the just the active isomer
of _____. They cause _____ of the blood vessels in the nose
you get decongestion.: ephedrine, constriction
140.
Cocaine blocks the catecholamine re-uptake system
thereby enhancing the effects of __released into the
synapse: NE
141.
______ = medical term describing an acute rapid decrease in
response to a drug after its administration. It can occur
after an initial dose or after a series of small dose:
Tachyphylaxis
142.
Since indirect acting and mixed acting stimulate the release
of catecholamines, with repetitive administration you can
eventually deplete catecholamines and see ______:
tachphylaxis
143.
I. Non-selective alpha adrenergic receptor antagonists
A. Covalent (haloalkylamines)
identify
131.
: A = AC3
B = Gs
C = Gq
D = IP3
E = cAMP
132.
Cocaine _____ vasopressor response to tyramine
and _______ response to norepinephrine: blocks, potentiates
133.
tyramine is an _____________ amine: indirect sympathiomimetic
Name 2: Phenoxybenzamine*
Dibenamine
144.
Phenoxybenzamine* is in what drug class?: I. Non-selective
alpha adrenergic receptor antagonists
A. Covalent (haloalkylamines)
145.
Dibenamine and phenoxybenzamine can both form
______________ and alkylate the alpha receptors. They form a
covalent complex with the alpha receptors which gives
persistent, non-reversible inactivation. You essentially have
to wait for the degradation of the receptor and its resynthesis for the actions of these drugs to be reversed.
There actions can persist for at least a day.: ethylene
immonium ions
149.
Beta-2, Alpha-1
alpha-1
146.
identify the two compounds in the deactivation process
: Ethylene iminium ion
Alkylated α-receptor
147.
at low doses of E you act primarily through ____ receptors in
the VSM and cause vasodilation, but at high doses of E you
activate both ___ an ____, the activation of _____ predominates
and you get vasoconstriction and a BP increase.: beta-2
150.
what happens when you treat with phenoxybenzamine
(POB) and block the alpha-1 receptors. This leaves only the
_____ response of Epinephrine, giving vasodilation and a
decrease in BP: beta-2
151.
Although phenoxybenzamine isn't used extensively
clinically, it is used occasionally for the treatment of ________.
This is a tumor of the adrenal medulla which results in
excessive levels of circulating catecholamines causing
hypertension.: pheochromocytoma
152.
pheochromocytoma is treated by which medication during
surgery?: phenoxybenzamine
153.
The pharmacological actions of these drugs are what you
would expect for blockade of alpha-adrenergic receptors:
1. You get a ________ in peripheral resistance and ______ in
cardiac output via reflex tachycardia. There is a relatively
small effect on BP when the patient is recumbent and but
larger effect when the patient is standing to postural
hypotension.
identify which is A &B?
what is phentolamine?
: NE = a
E=b
2. By blocking alpha receptors in other target organs they
can cause miosis and enter CNS where they can cause
these 2 SE?: decrease, increase
nausea and sedation
148.
Explain what "E reversal" is?: The lower plot shows what
happens when you treat with phenoxybenzamine (POB) and
block the alpha-1 receptors. This leaves only the beta-2
response, giving vasodilation and a decrease in BP. By
blocking the alpha-1 receptors we have converted this pressor
response to a depressor response.
The ability of alpha-antagonists to change the response to
high levels of E is often referred to as E reversal.
alpha blocker non-selective
154.
Noncovalent alpha blocker, name 2!: Phentolamine*
Tolazoline
155.
Tolazoline, class?: Non-covalent, Non-selective alpha
adrenergic receptor antagonists
156.
Phentolamine*, class?: Non-covalent, Non-selective alpha
adrenergic receptor antagonist
157.
158.
what drug was added?
: Phentolamine, could also be other drugs that block alpha
receptors
_____ alpha-1 antagonists such as phentolamine and a
___________ antagonist such as phenoxybenzamine.
163.
As you get the reflex increase in sympathetic activity due
to the______ in BP, you get an ______ in NE release which
activates Beta receptors in the heart to speed up HR.:
decrease, increase
164.
The presynaptic alpha-2 receptor is normally a feedback
mechanism which prevents too much NE release. When you
block the alpha-2 receptors with ___________ & ___________
(agents), you inhibit the normal feedback mechanism.
Consequently, you get more NE released than would occur
than if you did not have the alpha-adrenergic blocker
present: phentolamine or phenoxybenzamine
165.
You would like a drug to lower blood pressure that just
works on _____ receptors in vascular smooth muscle without
blocking presynaptic _____ receptors: alpha-1, alpha-2
166.
There is a group of drugs that are relatively specific for
alpha-1 receptors with low activity for alpha-2
receptors. These include?: Doxazosin
Prazosin*
Terazosin
167.
Doxazosin
Prazosin*
Terazosin
name whether they are reverisible/irreversible: reversible
nonreversible covalent
159.
This non-reversible blockade of alpha receptrors that you
get with the alkylating antagonists is sometimes referred to
as a _______________: non-equilibrium blockade
160.
The effects of phentolamine are generally what you would
expect for blocking alpha receptors. This includes what two
things?: postural hypotension, a reflex tachycardia due to the
vasodilation.
These are what class of drugs?: α1-selective alpha adrenergic
receptor antagonists
168.
prazosin, which is a ______ antagonist that has very low _____
activity.: reversible alpha-1, alpha-2
169.
Other related analogues include ______ & _______ which are
longer acting parazosin analogues.: terazosin and
doxazosine
170.
161.
indicate which type of alpha antagonist is present at A & B
: A = The dose response curve for NE stimulation of VSM is
shifted by phentolamine, but you can overcome the
competitive inhibition and reach the same effect by going to
higher levels of NE.
B=
In contrast, with an irreversible antagonist like
phenoxybenzamine you cannot overcome the effect with
higher levels of NE because you have effectively removed
alpha-1 receptors covalently.
162.
Some of this NE can act back onto the presynaptic _______
receptors which decreases the NE release. These
presynaptic alpha-2 receptors are coupled to inhibition of
______, lowers cAMP and decreases the release of NE: alpha2, adenylyl cyclase
which is phenoxybenzamine and which is prazosin?
: A = phenoxybenzamine
B = prazosin
171.
There is an alpha-2 specific antagonist, ___________: Yohimbinee
172.
Yohimbinee, class?: alpha-2 specific antagonist
173.
An alpha-2 specific antagonist that stimulates
production of ___ in the ___________ (part of the body): NO,
corpus cavernosum
174.
Yohimbine is used to treat? (2): erectile dysfunction in
males and hypoactive sexual desire disorder
175.
Nadolol*
176.
Propranolol*
class?: Non-selective ß-blockers
177.
Timolol*
class?: Non-selective ß-blockers
178.
Non-selective ß-blockers, name 3: Nadolol*
Propranolol*
Timolol*
189.
Why do ß blockers have anti-hypertensive action? (4): •
Block ß-receptors in heart decrease
cardiac output
• Decrease renin secretion from kidney
• Resets baroreceptor sensitivity
• Acts in CNS to "decrease" sympathetic activity
190.
Beta-blockers decrease intraoclular pressure by decreasing
the production of _______. Probably does this by acting on
betareceptors on the ciliary "processes" of the ciliary
epithelium.: aqueous humor
191.
T/F It has been shown that administration of propranolol or
timolol will decrease the incidence of second heart attacks
with cardiac patients.: T
192.
MAJOR SE of beta-blockers (7): Heart Failure
Bronchospasm
Heart Block
Bradycardia
Hypotension
Hypoglycemia
Claudication
193.
"other" side effects of beta blockers (7): Fatigue
Constipation
Diarrhea
Nightmares
Depression
Paresthesias
Skin Rash
194.
beta blockers are Dangerous if therapy stopped suddenly,
name SE that could occur: (angina, hypertension, tachycardia,
myocardial infarction)
195.
Why is the number of receptors a major factor that causes
the unwanted side effects of abruptly stopping betablocker therapy?: When patients are treated with propranolol
those up-regulated beta receptors are blocked but if you
rapidly stop treatment they are exposed and this leads to
supersensitivity to NE.... give the unpleasant effects.
class?: Non-selective ß-blockers
179.
Atenolol*
class?: ß1-Selective Antagonists
180.
Esmolol*
class?: ß1-Selective Antagonists
181.
Metoprolol*
class?: ß1-Selective Antagonists
182.
ß2-Selective Antagonists? (1): Butoxamine*
183.
ß1-Selective Antagonists? (3): Atenolol*
Esmolol*
Metoprolol*
184.
Butoxamine*
class?: ß2-Selective Antagonist
185.
What class of drugs are added at A & B which cause the
difference in effect of isoperterenol?
: A = phentolamine
B = propranolol (non selective Beta blocker)
186.
Propranolol and related drugs have an additional action
which can affect the rhythm of the heart, propranolol is
sometimes said to have a __________ effect. Somewhat like a
local anesthetic and it decreases __________________ activity:
"membrane-stabilizing"
excitability-antiarryhthmic
187.
Therapeutic use of propranolol in cardiac conditions (5):
HTN, angina, arrthymias, cardiomyopathy, hyperkinetic heart
188.
Therapeutic use of propranolol in endocrine conditions:
thyrotoxicosis
phaeochromacytosis
htn
Consequently, drugs such as Inderal are withdrawn
progressively. Since patients with graded withdrawal do not
show supersensitivity responses, it implies that there is return
of beta-receptors in heart to normal levels when the drug is
slowly withdrawn.
196.
So you can see that just applying a little timolol to the
asthmatic patient causes a very significant decrease in ____.
Remember that beta-2 receptors can mediate bronchial
smooth muscle ______.: FEV
relaxation
197.
Labetalol is a mixture of ___ stereoisomers. To which
receptors does it bind to?: four
nonselective beta blocker and a relatively specific for alpha-1.
198.
labetalol which is an alpha- and beta- adrenergic
antagonist, with higher affinity for ___ receptors.: beta
199.
Non-selective ß-blocker PLUS α1-selective
antagonist
206.
agent?: labetalol
200.
The effects of reserpine are what you expect for a drug
that changes levels of catecholamines this leads to _______ in
HR and BP, and an_______- in GI tone and motility.: decrease
201.
_______ can also cause depletion of catecholamines from
adrenergic neurons and in the CNS, consequently it can
cause sedation and depression.: Reserpine
If you pretreat with ______, smooth muscle contraction cause
by either pre or post-ganglionic stimulation is lost because
it inhibits the release of NE at the nerve terminal. The
effect of direct application of NE, is however, not affected.:
hexamethonium
increase
202.
If you pretreat with ___________, which blocks the transmission
across the sympathetic ganglia, you no longer get
preganglionic stimulation but still get SM contraction when
you stimulate post-ganglionically or when you stimulate
with NE.
bretylium
207.
Reserpine blocks vasopressor response to
_______ and but not to ______: tyramine
NE
203.
T/F Reserpine is active against sympathetic neurons, the
adenrenal medulla and the CNS. It also has cocaine-like
effects.: FALSE = no cocaine effects. only bretylium,
guanethidine
204.
T/F bretylium also blocks the cytoplasmic membrane
catecholamine uptake system and has "cocaine like
activity". Bretylium has no effects in the CNS or on the
adrenal medulla.: T
name the pretreatment of A & B either hexamethonium or
bretylium
: a = hexamethonium
b = bretylium
205.
208.
However, after treatment with______, NE release is blocked
and muscle contraction is blocked: guanethidine
209.
______is transported by uptake 1 into the presynaptic
terminal transported by norepinephrine transporter (NET).
(In this it competes with norepinephrine so can potentiate
exogenously applied norepinephrine.) It becomes
concentrated in norepinephrine transmitter vesicles,
replacing norepinephrine in these vesicles. This leads to a
gradual depletion of norepinephrine stores in the nerve
endings.: Guanethidine
210.
Guanethidine and guanadrel have been used in the
treatment of ______: hypertension
211.
apparent number of _______ receptors in the heart goes up
with long-term treatment of rats with guanethidine.: beta
212.
Clonidine is an ___________ agonist. It was discovered that
clonidine had some unexpected properties. This slide shows
the effect of clonidine on BP when it is injected IV or into
the cerebrospinal fluid (ICV).: alpha-adrenergic
answer yes/no
: A - yes
b - no
c- no
d - yes
e/f - no
g = no
h/i - yes
213.
When injected IV there is a transient increase in BP which you might expect for an alpha-adrenergic agonist, but this was
followed by a decrease in BP.
When you administer the drug to the cerebrospinal fluid, you only see a decrease in BP which is more pronounced and longerlasting. This is thought to be due to an effect in of clonidine in the ____. Clonidine can interact with ____ receptors to decrease
___________ output.: CNS
alpha-2, sympathetic
214.
When you give _____ BP starts to drop and at the same time electrical activity in the splanchnic nerve decreases. This provides
good evidence that ______(SAME BLANK) is activating centrally rather than peripherally: clonidine
215.
what electrical activity shows that clonidine works centrally and not periphereally?: electrical activity in the splanchnic nerve
decreases. This provides good evidence that clonidine activating centrally rather than peripherally
216.
which is the effect of clonidine?
:B
217.
_____________ an analogue of another drug it gets taken up into the nerve terminals and is concerted to alpha-methyl NE and
stored in granules. It is released upon neuronal stimulation and functions as a "false neurotransmitter". It lowers BP and is used
in the treatment of hypertension.: alpha-methyl dopa
218.
alpha-methyl dopa is used for treatment in what?: hypertension
219.
α-methylnorepinephrine is an _______ agonist:
acts in CNS to decrease sympathetic outflow: α 2-adrenergic
220.
α-methyldopa is used for the treatment of
______: hypertension