Exam 2 Flashcards
cox enzymes convert ___ into _____
convert aracadonic acid/ prostaglandin H2
what cofactor goes with alcohol dehydrogenase?
Zn2+
difunisal is
a cox inhibitor
frovatriptan is a
5-HT1 receptor agonist
what kind of enzyme is farnesyl diphosphate synthase?
transferase
farnesylated proteins are incorporated into proteins such as ____ and have effects on signaling through these
small GTPase proteins
EGFR complex with erlotinib is ___ inhibitor with respect to ATP
a competitive inhibitor
ketanserin is
a 5-HT2 antagonist
pamidrone is
a 2nd generation bisphosphonate
what enzyme do bisphosphynate drugs for the treatment of osteoporosis inhibit?
farnesyl diphosphate synthase
panitumumab is
an antibody to EGFR. Prevents EGFR signaling
PKC is
a serine/threonine kinase
for a noncompetitive inhibitor, Km
appears unaltered
Gefitinib is
a small molecule EGFR inhibitor
diltiazem is a _____ ______
benzothiazepine calcium channel blocker
alendronate is a ___ generation bisphosphonate
2nd
Cox __ inducible, primarily in __ during __
2/ macrophages/ inflammation
methyl salicylate is
a cox inhibitor
naratriptan is
a receptor 5-HT1 agonist
celecoxib is
a Cox inhibitor
a ________ is exposed in Cox-2, allowing for specificity
hydrophobic pocket
raloxifene is
an estrogen receptor antagonist
raloxifene is
a bisphosphonate
cetuximab is
an antibody to EGFR. prevents EGFR signaling
risedronate is ____ with respect to IPP
un-competitive
the NR3 subfamily includes the
steroid hormone receptors
mianserin is
a 5-HT2 antagonist
what cofactor goes with cytochromes?
Fe3+ or Fe2+
zolendronate is
a 3rd generation bisphosphonate
tamoxifen is
an estrogen receptor antagonist
risendronate is _____ with respect to GPP
competitive
Cox___ is constitutively expressed in most tissues
1
what cofactor goes with DNA polymerase?
Mg2+
sumatriptan is a
5-Ht1 receptor agonist
cyclooxygenases are also known as
prostaglandin H synthases
what cofactor goes with cytochrome oxidase?
Cu2+ or Cu+
prosatglandins bind to
GPCRs
what cofactor goes with carbonic anhydrase?
Zn2+
ATP –> ADP +Pi = what change in delta G?
-7.3 kcal/mol
asprin and ibuprofin are ______ inhibitors
Cox1 and Cox2
Erlotinib is
a small molecule EGFR inhibitor
what cofactor does HMG-CoA reductase use?
NADH
for an uncompetitive inhibitor, Km
is decreased
what cofactor goes with pyruvate phosphokinase?
Mg2+
rizatriptan is a
5-HT1 receptor agonist
temsirolimus = ______ and is
Torisel/ mTOR serine/ threonine kinase inhibitor
vorinostat is used to treat
T cell lymphoma
_______ ion channels are very important in the heart
voltage gated
mTOR is
a serine/threonine kinase
teriparatide is
a bisphosphonate
nifedipine is a _______ _______
dihydropyridine calcium channel blocker
do antineoplastic compounds bind covalently?
yes
3rd generation bisphosphonates have
aromatic groups that increase affinity for farnasyl diphosphate synthase
Src is
a cytoplasmic tyrosine kinase
do nitrosoureas bind DNA covalently?
yes
The R1 position of a bisphosphonate must be ___ –> this is necessary for interacting with the enzyme & with bone->”bone hook”
OH (hydroxyl group)
risedronate is a ____ generation bisphosphonate
3rd
alendronate is
a bisphosphonate
histone deacetylases are _____ enzymes
hydrolase
ENT transports
neucleotides
_______ increase bone mineral density
bisphosphonates
does mitomycin C bind DNA covalently?
yes
bisphosphonates decrease ______ activity
farnasylPP synthase and ultimately osteoclast
calcitonin is
a bisphosphonate
vorinostat = ______, also called ____. It is _____
Zolina/ SAHA/ a HDAC inhibitor
ibandronate is
a 2nd generation bisphosphonate
carcinomas are derived from ____ cells
epithelial
flecainide is a class ___ _______ and it is _____ wrt association/dissociation
Ic/ sodium channel blocker/ slow
chlorambucil forms
between strands cross-links
JAK-2 is
a cytoplasmic tyrosine kinase
imatinib = ______ and is
gleevec/ Abl tyrosine kinase inhibitor
Can GPCRs directly modify ion channels?
yes
exemestane is
an aromatase inhibitor
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
Her-2 is
a receptor tyrosine kinase
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
crizotinib = ______ and is
Xalkori/ ALK tyrosine kinase inhibitor
_______ ion channels are very important in the nervous system
ligand-gated
Gleevec is a drug for
chronic myeloid leukemia
AKT is
a serine/threonine kinase
JaK-2 is
a cytoplasmic tyrosine kinase
5-fluorouracil targets
thymdylate synthase
vemurafenib is a drug for
late stage melanoma in patients with a V600E mutation
topotecan targets
topoisomerase
vemurafenib = ________ and is
Zelboraf/ B-Raf serine/threonine kinase
histone deacetylases remove acetyl groups from _______ amino acid on a histone
lysine
Abl is
a cytoplasmic tyrosine kinase
etoposide targets
topoisomerase
exemestane is used for ER positive breast cancer if disease progresses after _____ therapy
tamoxifen
what kind of enzyme is aromatase?
oxidoreductase
acetylation removes _____ on the histones, so they ___
the positve charge/ interact less closely with DNA
cyclophosphamide targets
DNA
____________ are characteristic of irreversible inhibitors
covalent bonds
methotrexate targets
dihydrofolate reductase
dihydropyridine calcium channel blockers act on the _______ of the cell
outside
sarcomas are derived from ____ cells
mesencymal
exemestane ________ binds aromatase
irreversibly
dexamethasone targets
glucocorticoid receptor
IGF is
a receptor tyrosine kinase
doxorubicin targets
DNA
cisplatin is
an alkylating agent
lidocane is a class ______ _____ and it is _____ wrt association/dissociation
IB/ sodium channel blocker/ fast
melphalan is _____
an alkylating agent
what percent of proteins are druggable?
10-15
many drugs that covalently bind DNA are _______ agents that target __ of ____ that is exposed in the ___ groove of DNA
alkylating/ N7/ guanine/ major
what percent of proteins are disease modifying?
10-15%
purines are more ___ than pyrimidines
neucleophilic
quinidine is a class _____ _________ and it is ___ wrt association/dissociation
Ia/ sodium channel blocker/ intermediate
melphalan forms
between strands cross links
chlorambucil is
an alkylating agent
distamycin binds ___ with ______
the minor groove/ hydrogen bonding and hydrophobic interactions
calcium channel alpha 1 D is inhibited by
phenylalkylamines
do intercalators bind covalently?
no
what is the primary receptor type in the heart?
B1
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
parasympathetic: ___ preganglionic nerves and _____ post ganglionic nerves
long/ short
in vessels, cAMP cause _____ while PI causes ____
vaso-relaxation/ vasoconstriction
calcium channel alpha 1 C is inhibited by
dihydropyridines
do groove binders bind covalently?
no
calcium channel alpha 1 F is inhibited by
benzothiazepines
calcium channel alpha 1 D are in
endocrine
do nitrogen mustards bind DNA covalently?
yes
nicardipine is a ________ _____
dihydropyridine calcium channel blocker
saxitoxin is
a sodium channel blocker
dynemicin A does what?
binds to DNA and cleaves it
calcium channel alpha 1 F are in
retinal
Is saxitoxin extracellular or intracellular?
extracellular
do platinum complexes bind DNA covalently?
yes
the _____ system has a single nerve, no ganglia
somatic
class IA sodium channel blockers are __ and __
moderate/ elongate cell recovery after action potential
ABC transporters are ____ of ____
dimers/ 6 helices
what is the major use of calcium channels as drug targets?
to decrease blood pressure
P-gp= ___ = _____
ABCB1/ MDR1
verapamil is a _______ _______
phenylalkylamine calcium channel blocker
class IB sodium channel blockers are ____ and ____
weak/ shorten cell recovery after action potential
The ATP binding domain of an ABC transporter is
inside the cell
phenylalkylamine calcium channel blockers act on the _______ of the cell
inside
class IC sodium channel blockers are ____ and _____
strong/ cause no change to time for cell recovery after action potential
Penicillans are transported by
OAT
cis platin forms
intrastrand cross links
zidovudine is transported by
ENT1
folic acid is transported by
OAT
Voltage gated ion channels have ___ groups of _____ transmembrane domains
4/6
calcium channel alpha 1 C are in
cardiac muscle
minor groove binders bind _____ rich regions because
AT/ 2-amino group of guanine prevents binding to GC regions
dynemicin A combines ___ and ____
intercalation/ minor groove binding
Sodium channel blockers are used to treat ___, ____, ___ and as ____
cardiac arrhythmia/ high blood pressure/ epilepsy/ local anesthetics
netropsin binds _____ with ______
the minor groove/ hydrogen bonding and hydrophobic interactions
calcium channel alpha 1 S are in
skeletal muscle
metformin is transported by
OCT
sweat glands are unique because
though they are part of the sympathetic nervous system, the postganglionic nerves secrete Ach instead of NE
prostaglandins are transported by
OAT
_____ stabilize the inward facing state of PEPT1
extracellular salt bridges between arginine and glutamic acid
NSAIDs are transported by
OAT
choline is transported by
OCT
what kind of receptor is on sweat glands?
muscarinic
P-gp expression is regulated by
nuclear receptors
what percent of proteins interact with used drugs?
2%
PepT1 takes an amino acid or a small peptide and couples its transport to ___
H+ symport
nicotine is transported by
OCT
valacyclovir is a ______ substrate that is hydrolyzed to acyclovir once in the cell
Pept1
what neurotransmitter is involved with renal vascular smooth muscle?
dopamine
Zidovudine =
AZT
tight and narrow protein interactions give the ___ affinity
best
dopamine is transported by
OCT
________ activity stimulates glucose release by the liver
sympathetic
p53 binds to MDM2 using a ______, _____ binding cleft
deep/ hydrophobic
what kind of receptor is associated with parasympathetic nervous system?
muscarinic
do SLC transporters require ATP to function?
no
taxol binds tubulin via
hydrogen bonds and hydrophobic interactions
SLC transporters can be ___ or _____
facilitative transporters/ secondary active transporters
ACh receptor(s) of the CNS:
M & N
blood goes from the liver to the ______ heart, to the lungs, to the _______ heart
right/ left
OATP1 is _______ that ___
an SLC transporter/ absorbs statin drugs
ACh receptor(s) of the autonomic nervous system:
M & N
Do ABC transporters require ATP to function?
yes
in humans, ABC transporters generally
export
binding of ____ to ______ makes _____ inactive
Bcl-2, Bax/Bac, Bax/Bac
Bax/Bac precipitates
apoptotic cascade when it is free
cancer cells have up-regulated _____
Bcl2
taxol blocks
tubulin disassembly
list the layers on your head:
skin, periosteum, bone, dura mater, arachnoid mater, subarachnoid space (with CSF), pia mater, brain
_____ are the resident immune cells of the CNS
microglia
beta-tubulin binds
GTP that hydrolyzes to GDP
the _________ cells have tight junctions, making an active process necessary for the formation of cerebrospinal fluid
choroidal ependymal
___ form the epithelial lining of the ventricles in the CNS
ependymal cells
cAMP and PI are complementary when they both work to
stimulate glucose release from the liver
vinca alkaloids block
tubulin addembly
ACh receptor(s) of the NMJ:
N
Cytarabine =
AraC
what three things do muscarinic acetylcholine receptors do?
inhibit AC/ stimulate PLC/ regulate K+ channels
organophosphates and carbamates are used as
AChE-I
alpha-tubulin binds
GTP that does not hydrolyze
_______ provide metabolic support for the neurons in peripheral ganglia
satellite cells
You can counteract excessive Bcl production with
BH3 binding ligand
sympathetic: ____ preganglionic nerves and _____ post ganglionic nerves
short/ long
Cytarabine is transported by
ENT1
p53 blocks
BCl-2 function
p53 and ____ keep each other in check. In cancer you have too little p53 and too much _____
MDM2/ MDM2
COMT is found
outside the cell, in the synapse
what does cevimeline do and what is it?
increases salivation/ M3 agonist
_____ receptors: renal vasculature, dilation of blood vessels
D1
Ergots are
alpha blockers
______ receptors are involved in regulation of the tone of the CNS
alpha 2
Does B1 increase renin release?
yes
_____ receptors: fat cells, metabolic effects
B3
B2 receptor agonists cause broncho____
dilation
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
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
Alpha 1 agonists have _____ action on the heart, and they ___ heart rate.
Indirect/ decrease
Nitrous oxide ______ the GI tract
relaxes
Orthostatic hypotension is a side effect of ____
A1 blockers
_____ brings a positively charge group to stabilize the negative charge on oxygen, allowing carbon to act as ____
histidine/ an electrophile
Which receptor subtypes may be associated with early onset of smoking?
A5B4
What is the sympathetic effect of a ganglionic blocker?
vasodilation
how does aricept (donepezil) interact with AChE?
non covalent weak interactions, no acylation step
phenylethanolamine n-methyltransferase changes norepinephrine to
epinephrine
What is the most common form of nicotinic receptor subtypes?
A4B2
irreversible AChE-Is have
phosphate group
dopamine, epinephrine and norepinephrine are metabolized by _____ and _____
MAO/ COMT
alpha stimulation in the brain
reduces sympathetic activity
small groups on the alpha carbon of a catecholamine are tolerated and have the effect of
decreasing degradation by MAO
muscarinic stimulation in the CNS
increase sympathetic activity
nicotene’s positive charge is
reversible because it is hydrogenated
what system provides homeostatic regulation that is appropriate for whatever is going on in the body at that point in time?
the limbic system
the hypothalamus influences a lot of _____ function
autonomic
antimuscarinics ______ sweat
reduce
muscarine has an OH group - can it cross the blood brain barrier?
yes
alpha substitution of a catecholamine ___ the activity of direct-acting compounds and ______ the activity of indirect-acting compounds
reduces/ increases
GABAa receptor =
chloride channel
MAO is found
in the cell, in the mitochondria
in the AChE active site, there is a ____ hole looking for a ______ charge
negative/ positive
The _____ receptor in pain pathways responds to noxious stimuli, chemicals, and it is a Calcium channel
TRV1
Oxidative stress from inflammation, tissue injury modulates ___ which increase sensitivity of receptor
sulfhydryls
beta carbon hydroxylation of a catecholamine ____ activity of direct-acting agents, especially those acting at _____ receptors
increases/ Beta
direct desensitization effects:
change receptor number or sensitivity
indirect desensitization effects:
change sensitivity
The alpha 1 receptor acts via __ to increase ___ resulting in ___
phosphoinositide pathway/ increase intracellular concentration of calcium/ cause vasoconstriction
________ –>Renin–> _____ –>Angiotensin Converting Enzyme –> ______
Angiotensinogen/ Angiotensin I/ Angiotensin II
repeated cocaine decreases DA transporter ___
mRNA
At physiological concentrations, epinephrine primarily targets____. At high concentrations _____
B2 receptors/ it looses specificity and affects alpha
activated receptor-hormone complex alters
gene expression
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
would you use epinephrine or norepinephrine as a nasal decongestant?
epinephrine
Dopamine ________ heart contractility and ________ heart rate
increases/ doesn’t change
what is the parasympathetic effect of a ganglionic blocker?
tachycardia, constipation, urine retention
epinephrine has more _____ activity than norepinephrine
neta
Distributive (_________) shock: ___, ___, and _____ shock.
vasodilatory/ septic/ anaphylactic/ neurogenic
alpha 2 on presynaptic neuron acts to ____
reduce the release of NE
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
muscarinic agonists should have ____ atom capable of H bond
O
Beta 1 signaling: In heart, ____ activates __ that _______ causing _____
cAMP/ PK-A/ L-type calcium channels/ increased calcium entry into the cells
Acetylcholine is a neurotransmitter in the
CNS & PNS
B1: G_ protein coupled
s
In Beta 2 signaling in the vascular smooth muscle, _____ inhibits ____ causing _____
cAMP/ myosin light chain kinase/ less contractile force
atropine and scopolamine are
antimuscarinics
what are the three parts to acetylcholine?
acetyl group, ethylene bridge, quaternary amonium group
Beta 2 blockers found presynaptically
facilitate NE release
Dopamine B-hydroxylase changes dopamine to
norepinephrine
The size of alkyl groups on the N of a muscarinic agonist should not exceed ___
the size of a methyl
Is ACh water soluble?
Yes, very much so
will muscarinic agonists increase motility of GI and urinary tract?
yes
M2 –>
reduced heart rate
effective catecholamins should have ____ configuation at the beta carbon
R
for catecholamines, the substituent on the N
strongly influences receptor subtype affinity
what does MAO do to norepinephrine?
it replaces the amine with an aldehyde
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
methacholine chloride is selective for
muscarinic receptors
for a catecholamine, there should be at least one __ on the N
H
are epinephrine or norepinephrine orally bioavailable?
no
B2: G__ protein coupled
s
M3 –>
bronchiolar constriction, GI contraction, vascular relaxation, increased secretions
NO diffuses from ____ to _____ and activates ______, which produces __, resulting in ___
endothelial cells/ smooth muscle cells/ guanylate cyclase/ cGMP/ dilation of blood vessel
hydroxyl substituent at C3 of a catecholamine ring favors ____ selectivity
alpha
what can you give to treat myasthenia gravis?
an acetylcholinesterase inhibitor
is d-tubocurarine depolarizing?
no
does a carbamate terminus on acetylcholine make it selective? more resistant to nydrolysis?
no, yes
solanaceous alkaloids are
Ach antagonists
N1 –>
skeletal muscle, contraction
ganglionic blockers should be able to cross
the blood brain barrier
as you increase electron donors on the carbonyl group of acetylcholine, you
slow down electrophilic attack
acetylcholine receptors have a ____ pocket as well as lots of ____
negative/ hydrophobicity
d-tubocurarine is
a neuromuscular junction blocker
would an ideal nmj blocker be rapidly eliminated?
yes
does beta carbon hydroxylation of a catecholamine reduce the dutation of action?
yes, somewhat
the most important effect of hydrozyls on the ring of a catecholamine is
to provide direct action at postsynaptic receptors
unlike other antimuscarinic agents, _____ acts as a CNS depressant at therapeutic doses
scopolamine
tyrosine hydroxylase changes tyrosine to
DOPA
you can use ________ for asthma treatment
anticholinergics
succinylcholine chloride is a ____ _____
depolarizing NMJ blocker
In myasthenia gravis, ________ is produced and ________ resulting in ____
an antibody to the nicotinic receptor/ acethylcholine cannot stimulate the receptor/ muscle weakness and paralysis
catecholamine synthesis starts with
tyrosine
Atropa belladonna is
an ACh antagonist
Ar-NH - imidazoline ring =
alpha 2 agonist
_________ prevents the release of acetylcholine
botox
ganglionic blockers act in the
CNS
muscarine’s positive charge is
permanent because it has 4 R groups
would an ideal NMJ blocker be depolarizing?
no
non H-bonding substituents on the ring of a catecholamine tend to
produce antagonists
would an ideal nmj blocker be metabolically inactivated?
yes
AR - CH2 - imidazoline ring =
alpha1 agonist
Aromatic L-amino acid decarboxylase changes DOPA to
dopamine
AChE has a _____ pocket, and a ____ pocket
negatively charged/ hydrophobic
A2: G_ protein coupled
i
hydroxyl substituent at C4 of a catecholamine ring favors ____ selectivity
beta
