Exam 2 Flashcards
1
Q
cox enzymes convert ___ into _____
A
convert aracadonic acid/ prostaglandin H2
2
Q
what cofactor goes with alcohol dehydrogenase?
A
Zn2+
3
Q
difunisal is
A
a cox inhibitor
4
Q
frovatriptan is a
A
5-HT1 receptor agonist
5
Q
what kind of enzyme is farnesyl diphosphate synthase?
A
transferase
6
Q
farnesylated proteins are incorporated into proteins such as ____ and have effects on signaling through these
A
small GTPase proteins
7
Q
EGFR complex with erlotinib is ___ inhibitor with respect to ATP
A
a competitive inhibitor
8
Q
ketanserin is
A
a 5-HT2 antagonist
9
Q
pamidrone is
A
a 2nd generation bisphosphonate
10
Q
what enzyme do bisphosphynate drugs for the treatment of osteoporosis inhibit?
A
farnesyl diphosphate synthase
11
Q
panitumumab is
A
an antibody to EGFR. Prevents EGFR signaling
12
Q
PKC is
A
a serine/threonine kinase
13
Q
for a noncompetitive inhibitor, Km
A
appears unaltered
14
Q
Gefitinib is
A
a small molecule EGFR inhibitor
15
Q
diltiazem is a _____ ______
A
benzothiazepine calcium channel blocker
16
Q
alendronate is a ___ generation bisphosphonate
A
2nd
17
Q
Cox __ inducible, primarily in __ during __
A
2/ macrophages/ inflammation
18
Q
methyl salicylate is
A
a cox inhibitor
19
Q
naratriptan is
A
a receptor 5-HT1 agonist
20
Q
celecoxib is
A
a Cox inhibitor
21
Q
a ________ is exposed in Cox-2, allowing for specificity
A
hydrophobic pocket
22
Q
raloxifene is
A
an estrogen receptor antagonist
23
Q
raloxifene is
A
a bisphosphonate
24
Q
cetuximab is
A
an antibody to EGFR. prevents EGFR signaling
25
risedronate is ____ with respect to IPP
un-competitive
26
the NR3 subfamily includes the
steroid hormone receptors
27
mianserin is
a 5-HT2 antagonist
28
what cofactor goes with cytochromes?
Fe3+ or Fe2+
29
zolendronate is
a 3rd generation bisphosphonate
30
tamoxifen is
an estrogen receptor antagonist
31
risendronate is _____ with respect to GPP
competitive
32
Cox___ is constitutively expressed in most tissues
1
33
what cofactor goes with DNA polymerase?
Mg2+
34
sumatriptan is a
5-Ht1 receptor agonist
35
cyclooxygenases are also known as
prostaglandin H synthases
36
what cofactor goes with cytochrome oxidase?
Cu2+ or Cu+
37
prosatglandins bind to
GPCRs
38
what cofactor goes with carbonic anhydrase?
Zn2+
39
ATP --> ADP +Pi = what change in delta G?
-7.3 kcal/mol
40
asprin and ibuprofin are ______ inhibitors
Cox1 and Cox2
41
Erlotinib is
a small molecule EGFR inhibitor
42
what cofactor does HMG-CoA reductase use?
NADH
43
for an uncompetitive inhibitor, Km
is decreased
44
what cofactor goes with pyruvate phosphokinase?
Mg2+
45
rizatriptan is a
5-HT1 receptor agonist
46
temsirolimus = ______ and is
Torisel/ mTOR serine/ threonine kinase inhibitor
47
vorinostat is used to treat
T cell lymphoma
48
_______ ion channels are very important in the heart
voltage gated
49
mTOR is
a serine/threonine kinase
50
teriparatide is
a bisphosphonate
51
nifedipine is a _______ _______
dihydropyridine calcium channel blocker
52
do antineoplastic compounds bind covalently?
yes
53
3rd generation bisphosphonates have
aromatic groups that increase affinity for farnasyl diphosphate synthase
54
Src is
a cytoplasmic tyrosine kinase
55
do nitrosoureas bind DNA covalently?
yes
56
The R1 position of a bisphosphonate must be ___ --> this is necessary for interacting with the enzyme & with bone->"bone hook"
OH (hydroxyl group)
57
risedronate is a ____ generation bisphosphonate
3rd
58
alendronate is
a bisphosphonate
59
histone deacetylases are _____ enzymes
hydrolase
60
ENT transports
neucleotides
61
_______ increase bone mineral density
bisphosphonates
62
does mitomycin C bind DNA covalently?
yes
63
bisphosphonates decrease ______ activity
farnasylPP synthase and ultimately osteoclast
64
calcitonin is
a bisphosphonate
65
vorinostat = ______, also called ____. It is _____
Zolina/ SAHA/ a HDAC inhibitor
66
ibandronate is
a 2nd generation bisphosphonate
67
carcinomas are derived from ____ cells
epithelial
68
flecainide is a class ___ _______ and it is _____ wrt association/dissociation
Ic/ sodium channel blocker/ slow
69
chlorambucil forms
between strands cross-links
70
JAK-2 is
a cytoplasmic tyrosine kinase
71
imatinib = ______ and is
gleevec/ Abl tyrosine kinase inhibitor
72
Can GPCRs directly modify ion channels?
yes
73
exemestane is
an aromatase inhibitor
74
phosphorylation by ___ or ___ on the inside of the cell at the voltage gated ionchannel can affect the magnitude of voltage needed to affect a change or can inactivate the channel
PKA/ PKC
75
Her-2 is
a receptor tyrosine kinase
76
the ____ transmembrane domain is most important for determining change in voltage - change in conformation of ___ transmembrane domain leads to conformational change and opening of pore
4th/ 4th
77
crizotinib = ______ and is
Xalkori/ ALK tyrosine kinase inhibitor
78
_______ ion channels are very important in the nervous system
ligand-gated
79
Gleevec is a drug for
chronic myeloid leukemia
80
AKT is
a serine/threonine kinase
81
JaK-2 is
a cytoplasmic tyrosine kinase
82
5-fluorouracil targets
thymdylate synthase
83
vemurafenib is a drug for
late stage melanoma in patients with a V600E mutation
84
topotecan targets
topoisomerase
85
vemurafenib = ________ and is
Zelboraf/ B-Raf serine/threonine kinase
86
histone deacetylases remove acetyl groups from _______ amino acid on a histone
lysine
87
Abl is
a cytoplasmic tyrosine kinase
88
etoposide targets
topoisomerase
89
exemestane is used for ER positive breast cancer if disease progresses after _____ therapy
tamoxifen
90
what kind of enzyme is aromatase?
oxidoreductase
91
acetylation removes _____ on the histones, so they ___
the positve charge/ interact less closely with DNA
92
cyclophosphamide targets
DNA
93
____________ are characteristic of irreversible inhibitors
covalent bonds
94
methotrexate targets
dihydrofolate reductase
95
dihydropyridine calcium channel blockers act on the _______ of the cell
outside
96
sarcomas are derived from ____ cells
mesencymal
97
exemestane ________ binds aromatase
irreversibly
98
dexamethasone targets
glucocorticoid receptor
99
IGF is
a receptor tyrosine kinase
100
doxorubicin targets
DNA
101
cisplatin is
an alkylating agent
102
lidocane is a class ______ _____ and it is _____ wrt association/dissociation
IB/ sodium channel blocker/ fast
103
melphalan is _____
an alkylating agent
104
what percent of proteins are druggable?
10-15
105
many drugs that covalently bind DNA are _______ agents that target __ of ____ that is exposed in the ___ groove of DNA
alkylating/ N7/ guanine/ major
106
what percent of proteins are disease modifying?
10-15%
107
purines are more ___ than pyrimidines
neucleophilic
108
quinidine is a class _____ _________ and it is ___ wrt association/dissociation
Ia/ sodium channel blocker/ intermediate
109
melphalan forms
between strands cross links
110
chlorambucil is
an alkylating agent
111
distamycin binds ___ with ______
the minor groove/ hydrogen bonding and hydrophobic interactions
112
calcium channel alpha 1 D is inhibited by
phenylalkylamines
113
do intercalators bind covalently?
no
114
what is the primary receptor type in the heart?
B1
115
calcium channel blockers work by
blocking the part of the cardiac action potential that depends on calcium influx, and also by causing blood vessels to dilate
116
parasympathetic: ___ preganglionic nerves and _____ post ganglionic nerves
long/ short
117
in vessels, cAMP cause _____ while PI causes ____
vaso-relaxation/ vasoconstriction
118
calcium channel alpha 1 C is inhibited by
dihydropyridines
119
do groove binders bind covalently?
no
120
calcium channel alpha 1 F is inhibited by
benzothiazepines
121
calcium channel alpha 1 D are in
endocrine
122
do nitrogen mustards bind DNA covalently?
yes
123
nicardipine is a ________ _____
dihydropyridine calcium channel blocker
124
saxitoxin is
a sodium channel blocker
125
dynemicin A does what?
binds to DNA and cleaves it
126
calcium channel alpha 1 F are in
retinal
127
Is saxitoxin extracellular or intracellular?
extracellular
128
do platinum complexes bind DNA covalently?
yes
129
the _____ system has a single nerve, no ganglia
somatic
130
class IA sodium channel blockers are __ and __
moderate/ elongate cell recovery after action potential
131
ABC transporters are ____ of ____
dimers/ 6 helices
132
what is the major use of calcium channels as drug targets?
to decrease blood pressure
133
P-gp= ___ = _____
ABCB1/ MDR1
134
verapamil is a _______ _______
phenylalkylamine calcium channel blocker
135
class IB sodium channel blockers are ____ and ____
weak/ shorten cell recovery after action potential
136
The ATP binding domain of an ABC transporter is
inside the cell
137
phenylalkylamine calcium channel blockers act on the _______ of the cell
inside
138
class IC sodium channel blockers are ____ and _____
strong/ cause no change to time for cell recovery after action potential
139
Penicillans are transported by
OAT
140
cis platin forms
intrastrand cross links
141
zidovudine is transported by
ENT1
142
folic acid is transported by
OAT
143
Voltage gated ion channels have ___ groups of _____ transmembrane domains
4/6
144
calcium channel alpha 1 C are in
cardiac muscle
145
minor groove binders bind _____ rich regions because
AT/ 2-amino group of guanine prevents binding to GC regions
146
dynemicin A combines ___ and ____
intercalation/ minor groove binding
147
Sodium channel blockers are used to treat ___, ____, ___ and as ____
cardiac arrhythmia/ high blood pressure/ epilepsy/ local anesthetics
148
netropsin binds _____ with ______
the minor groove/ hydrogen bonding and hydrophobic interactions
149
calcium channel alpha 1 S are in
skeletal muscle
150
metformin is transported by
OCT
151
sweat glands are unique because
though they are part of the sympathetic nervous system, the postganglionic nerves secrete Ach instead of NE
152
prostaglandins are transported by
OAT
153
_____ stabilize the inward facing state of PEPT1
extracellular salt bridges between arginine and glutamic acid
154
NSAIDs are transported by
OAT
155
choline is transported by
OCT
156
what kind of receptor is on sweat glands?
muscarinic
157
P-gp expression is regulated by
nuclear receptors
158
what percent of proteins interact with used drugs?
2%
159
PepT1 takes an amino acid or a small peptide and couples its transport to ___
H+ symport
160
nicotine is transported by
OCT
161
valacyclovir is a ______ substrate that is hydrolyzed to acyclovir once in the cell
Pept1
162
what neurotransmitter is involved with renal vascular smooth muscle?
dopamine
163
Zidovudine =
AZT
164
tight and narrow protein interactions give the ___ affinity
best
165
dopamine is transported by
OCT
166
________ activity stimulates glucose release by the liver
sympathetic
167
p53 binds to MDM2 using a ______, _____ binding cleft
deep/ hydrophobic
168
what kind of receptor is associated with parasympathetic nervous system?
muscarinic
169
do SLC transporters require ATP to function?
no
170
taxol binds tubulin via
hydrogen bonds and hydrophobic interactions
171
SLC transporters can be ___ or _____
facilitative transporters/ secondary active transporters
172
ACh receptor(s) of the CNS:
M & N
173
blood goes from the liver to the ______ heart, to the lungs, to the _______ heart
right/ left
174
OATP1 is _______ that ___
an SLC transporter/ absorbs statin drugs
175
ACh receptor(s) of the autonomic nervous system:
M & N
176
Do ABC transporters require ATP to function?
yes
177
in humans, ABC transporters generally
export
178
binding of ____ to ______ makes _____ inactive
Bcl-2, Bax/Bac, Bax/Bac
179
Bax/Bac precipitates
apoptotic cascade when it is free
180
cancer cells have up-regulated _____
Bcl2
181
taxol blocks
tubulin disassembly
182
list the layers on your head:
skin, periosteum, bone, dura mater, arachnoid mater, subarachnoid space (with CSF), pia mater, brain
183
_____ are the resident immune cells of the CNS
microglia
184
beta-tubulin binds
GTP that hydrolyzes to GDP
185
the _________ cells have tight junctions, making an active process necessary for the formation of cerebrospinal fluid
choroidal ependymal
186
___ form the epithelial lining of the ventricles in the CNS
ependymal cells
187
cAMP and PI are complementary when they both work to
stimulate glucose release from the liver
188
vinca alkaloids block
tubulin addembly
189
ACh receptor(s) of the NMJ:
N
190
Cytarabine =
AraC
191
what three things do muscarinic acetylcholine receptors do?
inhibit AC/ stimulate PLC/ regulate K+ channels
192
organophosphates and carbamates are used as
AChE-I
193
alpha-tubulin binds
GTP that does not hydrolyze
194
_______ provide metabolic support for the neurons in peripheral ganglia
satellite cells
195
You can counteract excessive Bcl production with
BH3 binding ligand
196
sympathetic: ____ preganglionic nerves and _____ post ganglionic nerves
short/ long
197
Cytarabine is transported by
ENT1
198
p53 blocks
BCl-2 function
199
p53 and ____ keep each other in check. In cancer you have too little p53 and too much _____
MDM2/ MDM2
200
COMT is found
outside the cell, in the synapse
201
what does cevimeline do and what is it?
increases salivation/ M3 agonist
202
_____ receptors: renal vasculature, dilation of blood vessels
D1
203
Ergots are
alpha blockers
204
______ receptors are involved in regulation of the tone of the CNS
alpha 2
205
Does B1 increase renin release?
yes
206
_____ receptors: fat cells, metabolic effects
B3
207
B2 receptor agonists cause broncho____
dilation
208
why are long acting beta agonist long acting?
they have a long side chain that binds to a site near the receptor - if the drug comes off it is still nearby and so has the opportunity to come back and bind again
209
AChE is a ___ protease - the ____ group on the ____ acts as a ____. The ___ group is transferred to ____, then water breaks that bone
serine/ hydroxyl/ serine/ neucleophile/ acyl/ serine
210
Alpha 1 agonists have _____ action on the heart, and they ___ heart rate.
Indirect/ decrease
211
Nitrous oxide ______ the GI tract
relaxes
212
Orthostatic hypotension is a side effect of ____
A1 blockers
213
_____ brings a positively charge group to stabilize the negative charge on oxygen, allowing carbon to act as ____
histidine/ an electrophile
214
Which receptor subtypes may be associated with early onset of smoking?
A5B4
215
What is the sympathetic effect of a ganglionic blocker?
vasodilation
216
how does aricept (donepezil) interact with AChE?
non covalent weak interactions, no acylation step
217
phenylethanolamine n-methyltransferase changes norepinephrine to
epinephrine
218
What is the most common form of nicotinic receptor subtypes?
A4B2
219
irreversible AChE-Is have
phosphate group
220
dopamine, epinephrine and norepinephrine are metabolized by _____ and _____
MAO/ COMT
221
alpha stimulation in the brain
reduces sympathetic activity
222
small groups on the alpha carbon of a catecholamine are tolerated and have the effect of
decreasing degradation by MAO
223
muscarinic stimulation in the CNS
increase sympathetic activity
224
nicotene's positive charge is
reversible because it is hydrogenated
225
what system provides homeostatic regulation that is appropriate for whatever is going on in the body at that point in time?
the limbic system
226
the hypothalamus influences a lot of _____ function
autonomic
227
antimuscarinics ______ sweat
reduce
228
muscarine has an OH group - can it cross the blood brain barrier?
yes
229
alpha substitution of a catecholamine ___ the activity of direct-acting compounds and ______ the activity of indirect-acting compounds
reduces/ increases
230
GABAa receptor =
chloride channel
231
MAO is found
in the cell, in the mitochondria
232
in the AChE active site, there is a ____ hole looking for a ______ charge
negative/ positive
233
The _____ receptor in pain pathways responds to noxious stimuli, chemicals, and it is a Calcium channel
TRV1
234
Oxidative stress from inflammation, tissue injury modulates ___ which increase sensitivity of receptor
sulfhydryls
235
beta carbon hydroxylation of a catecholamine ____ activity of direct-acting agents, especially those acting at _____ receptors
increases/ Beta
236
direct desensitization effects:
change receptor number or sensitivity
237
indirect desensitization effects:
change sensitivity
238
The alpha 1 receptor acts via __ to increase ___ resulting in ___
phosphoinositide pathway/ increase intracellular concentration of calcium/ cause vasoconstriction
239
________ -->Renin--> _____ -->Angiotensin Converting Enzyme --> ______
Angiotensinogen/ Angiotensin I/ Angiotensin II
240
repeated cocaine decreases DA transporter ___
mRNA
241
At physiological concentrations, epinephrine primarily targets____. At high concentrations _____
B2 receptors/ it looses specificity and affects alpha
242
activated receptor-hormone complex alters
gene expression
243
B1 works indirectly to increase blood pressure through
stimulating renin which is involved in the production of Angiotensin II, which causes an increase in blood pressure
244
would you use epinephrine or norepinephrine as a nasal decongestant?
epinephrine
245
Dopamine ________ heart contractility and ________ heart rate
increases/ doesn't change
246
what is the parasympathetic effect of a ganglionic blocker?
tachycardia, constipation, urine retention
247
epinephrine has more _____ activity than norepinephrine
neta
248
Distributive (_________) shock: ___, ___, and _____ shock.
vasodilatory/ septic/ anaphylactic/ neurogenic
249
alpha 2 on presynaptic neuron acts to ____
reduce the release of NE
250
D1 receptor is a ____ receptor that causes activation of ____, It acts on blood vessels to cause _____, and _____ blood supply to the kidney
G protein coupled/ AC and cAMP/ vasodilation/ increase
251
muscarinic agonists should have ____ atom capable of H bond
O
252
Beta 1 signaling: In heart, ____ activates __ that _______ causing _____
cAMP/ PK-A/ L-type calcium channels/ increased calcium entry into the cells
253
Acetylcholine is a neurotransmitter in the
CNS & PNS
254
B1: G_ protein coupled
s
255
In Beta 2 signaling in the vascular smooth muscle, _____ inhibits ____ causing _____
cAMP/ myosin light chain kinase/ less contractile force
256
atropine and scopolamine are
antimuscarinics
257
what are the three parts to acetylcholine?
acetyl group, ethylene bridge, quaternary amonium group
258
Beta 2 blockers found presynaptically
facilitate NE release
259
Dopamine B-hydroxylase changes dopamine to
norepinephrine
260
The size of alkyl groups on the N of a muscarinic agonist should not exceed ___
the size of a methyl
261
Is ACh water soluble?
Yes, very much so
262
will muscarinic agonists increase motility of GI and urinary tract?
yes
263
M2 -->
reduced heart rate
264
effective catecholamins should have ____ configuation at the beta carbon
R
265
for catecholamines, the substituent on the N
strongly influences receptor subtype affinity
266
what does MAO do to norepinephrine?
it replaces the amine with an aldehyde
267
As you increase the size of the R group on the N of a catacholamine, you ______ the beta activity and _____ the alpha activity
increase/ decrease
268
methacholine chloride is selective for
muscarinic receptors
269
for a catecholamine, there should be at least one __ on the N
H
270
are epinephrine or norepinephrine orally bioavailable?
no
271
B2: G__ protein coupled
s
272
M3 -->
bronchiolar constriction, GI contraction, vascular relaxation, increased secretions
273
NO diffuses from ____ to _____ and activates ______, which produces __, resulting in ___
endothelial cells/ smooth muscle cells/ guanylate cyclase/ cGMP/ dilation of blood vessel
274
hydroxyl substituent at C3 of a catecholamine ring favors ____ selectivity
alpha
275
what can you give to treat myasthenia gravis?
an acetylcholinesterase inhibitor
276
is d-tubocurarine depolarizing?
no
277
does a carbamate terminus on acetylcholine make it selective? more resistant to nydrolysis?
no, yes
278
solanaceous alkaloids are
Ach antagonists
279
N1 -->
skeletal muscle, contraction
280
ganglionic blockers should be able to cross
the blood brain barrier
281
as you increase electron donors on the carbonyl group of acetylcholine, you
slow down electrophilic attack
282
acetylcholine receptors have a ____ pocket as well as lots of ____
negative/ hydrophobicity
283
d-tubocurarine is
a neuromuscular junction blocker
284
would an ideal nmj blocker be rapidly eliminated?
yes
285
does beta carbon hydroxylation of a catecholamine reduce the dutation of action?
yes, somewhat
286
the most important effect of hydrozyls on the ring of a catecholamine is
to provide direct action at postsynaptic receptors
287
unlike other antimuscarinic agents, _____ acts as a CNS depressant at therapeutic doses
scopolamine
288
tyrosine hydroxylase changes tyrosine to
DOPA
289
you can use ________ for asthma treatment
anticholinergics
290
succinylcholine chloride is a ____ _____
depolarizing NMJ blocker
291
In myasthenia gravis, ________ is produced and ________ resulting in ____
an antibody to the nicotinic receptor/ acethylcholine cannot stimulate the receptor/ muscle weakness and paralysis
292
catecholamine synthesis starts with
tyrosine
293
Atropa belladonna is
an ACh antagonist
294
Ar-NH - imidazoline ring =
alpha 2 agonist
295
_________ prevents the release of acetylcholine
botox
296
ganglionic blockers act in the
CNS
297
muscarine's positive charge is
permanent because it has 4 R groups
298
would an ideal NMJ blocker be depolarizing?
no
299
non H-bonding substituents on the ring of a catecholamine tend to
produce antagonists
300
would an ideal nmj blocker be metabolically inactivated?
yes
301
AR - CH2 - imidazoline ring =
alpha1 agonist
302
Aromatic L-amino acid decarboxylase changes DOPA to
dopamine
303
AChE has a _____ pocket, and a ____ pocket
negatively charged/ hydrophobic
304
A2: G_ protein coupled
i
305
hydroxyl substituent at C4 of a catecholamine ring favors ____ selectivity
beta
