Review for the Test
Feb 24, 2016
Review for the Test
The Test
• 57 Questions/Need to Answer 55• 27 My Section• 9.30-11.30p?
– 1-2 minutes/question
COX-2 Physiological Role
• Renin-angiotensin system• blood pressure and fluid balance
• Ovulation and labor• Wound healing
• Vascular endothelium• Vascular remodeling
Modified PGs (mostly)
• Block w-oxidation– Methyls at 15 and/or 16– Phenyl in 17-20 range
• Increase Lipophilicity– Add methyls, phenyls and esters
ADME: Metabolism
E=Esterase, O=Oxidation, R=Reduction, b=b-Oxidation, w=w-Oxidation, D=dealkylation, G=glucuronidation
E
E
R13
14
O
15
E
R13
1415
O
b
D
G
b
Talfuprost
E
R13
14
b
b
w
Prevents Beta-oxidaton
Overview
• Prostaglandins (PGs) and Thromboxanes (TXs)• NSAIDs• Gout
PGs and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
What Prostaglandin is this?A. PGE1B. PGE2C. PGF2alphaD. PGG2E. PGH2F. PGI2G. TXA2
PGE1PGE2
PGF2alpha
PGG2PGH2
PGI2TXA2
47%
12%
21%
3%3%
15%
0%
What Prostaglandin is this?
A. PGE1B. PGE2C. PGF2alphaD. PGG2E. PGH2F. PGI2G. TXA2
PGE1PGE2
PGF2alpha
PGG2PGH2
PGI2TXA2
10%7%
2% 2%
67%
5%7%
What Prostaglandin is this?A. PGE1B. PGE2C. PGF2alphaD. PGG2E. PGH2F. PGI2G. TXA2
PGE1PGE2
PGF2alpha
PGG2PGH2
PGI2TXA2
0%
7%
0%
61%
11%7%
14%
PG and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
Select the one that is not true
A. PGE2 relaxes vascular smooth muscle
B. TXA2 increases renal blood flow
C. PGI2 protects the gastric mucosa
D. PGF2alpha contracts uterine smooth muscles
E. PGF2alpha causes bronchoconstriction
PGE2 relaxe
s vascu
lar sm...
TXA2 incre
ases renal b
loo...
PGI2 protects
the gastr
ic...
PGF2alpha co
ntracts
uteri..
PGF2alpha ca
uses bronc..
.
0%
29%
39%
25%
7%
PG and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
Prostaglandin signaling within the cell is?
A. EndocrineB. AutocrineC. ParacrineD. Intracrine
Endocrine
Autocrine
Paracri
ne
Intracri
ne
33%
40%
11%16%
What are not involved in Prostaglandin and Thromboxane signaling
A. Plasma membrane bound GPCRs
B. Nuclear membrane bound GPCRs
C. Nuclear ReceptorsD. OATP transporter
Plasma m
embrane boun...
Nuclear m
embrane boun...
Nuclear R
ecepto
rs
OATP tr
ansporte
r
11%
24%
34%32%
Prostaglandin E2 (PGE2) binds to what type of receptor
A. DP1B. EP1C. FPD. IPE. TP
DP1EP1 FP IP TP
2%
63%
5%
16%14%
PG and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
What ways are PG and TX transported
A. Active EffluxB. Active InfluxC. Passive DiffusionD. All the above
Active
Efflux
Active
Influx
Passive Diffusio
n
All the above
10%
79%
7%5%
PG and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
The substrate of COX 2 is?
A. Arachidonic AcidB. PGE1C. PGE2D. PGF2alphaE. PGG2F. PGH2G. PGI2H. TXA2
Arachidonic A
cidPGE1
PGE2
PGF2alp
haPGG2
PGH2PGI2
TXA2
57%
0% 0%2%
4%
24%
9%
4%
The product of COX 2 is?
A. Arachidonic AcidB. PGE1C. PGE2D. PGF2alphaE. PGG2F. PGH2G. PGI2H. TXA2
Arachidonic A
cidPGE1
PGE2
PGF2alp
haPGG2
PGH2PGI2
TXA2
0%
7% 7%
28%
2%
19%
30%
7%
What is not a mechanism of metabolism for PG?
A. alpha-oxidation B. beta-oxidationC. omega-oxidationD. reductionE. alcohol
dehydrogenation
alpha-oxidation
beta-oxidation
omega-oxid
ation
reduction
alcohol d
ehydroge
nation
47%
0%
29%
13%11%
How is TXB2 produced
A. reductionB. oxidationC. hydrolysis D. conjugation
reduction
oxidati
on
hydrolysis
conjuga
tion
16%11%
27%
45%
Which Cytochrome P450 (CYP) is involved in w-oxidation?
A. CYP1A1B. CYP2C9C. CYP3A4D. CYP4A
CYP1A1
CYP2C9
CYP3A4CYP4A
4%
20%
39%37%
PG and TXs
• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs
NSAIDs will interfere with PG drugs because they can
A. Inhibit PG synthetasesB. Induce COX 2 expressionC. Reduce COX 2 expressionD. Inhibit COX 1E. Inhibit COX 2F. D and E
diclofenacInhibit P
G synthetas
es
Induce COX 2 exp
ression
Reduce COX 2 exp
ression
Inhibit COX 1
Inhibit COX 2
D and E
2% 0%
96%
0%0%2%
What prostaglandin is Aprostadil?A. PGE1
B. PGE2
C. TXA2
D. Prostacyclin onlyE. PGI2 onlyF. Prostacyclin and PGI2
Aprostadil
PGE1PGE2
TXA2
Prostacyclin
only
PGI2 only
Prostacyclin
and PGI2
77%
10%
0%
8%2%2%
What is not a use of Aprostadil
A. Erectile dysfunctionB. Congenital hear
defectC. HypertensionD. Induce laborE. A and BF. C and D
Erectile dysfu
nction
Congenita
l hear d
efect
Hypertensio
n
Induce la
bor
A and B
C and D
9%
32%
38%
9%
2%
11%
Aprostadil binding to a GPCR causes all but the following
A. Increase intracellular Ca2+
B. Decrease intracellular Ca2+
C. Activate adenylate cyclase
D. Increase cAMP
Increase
intra
cellu
lar Ca2
+
Decrease
intra
cellu
lar Ca2+
Activa
te adenyla
te cycla
se
Increase
cAMP
22%
4%0%
73%
What are not formulations of Alprostadil?
A. IV injectionB. Penile injectionC. OralD. Urethral
Suppository
IV injecti
on
Penile in
jection
Oral
Urethral Supposit
ory
9% 13%
78%
0%
What are ADR of Alprostadil?
A. Pain/RashB. Light HeadedC. Bleeding and
BruisingD. Flu SymptomsE. All the above
Pain/R
ash
Light H
eaded
Bleeding and Bruising
Flu Symptoms
All the above
2% 4%
91%
0%2%
Talfluprost
The compounds on the previous pageare modified versions of what prostaglandin?
A. PGE1
B. PGE2
C. TXA2
D. PGF2a
E. PGI2
F. 15-methyl PGF2a
PGE1PGE2
TXA2PGF2
aPGI2
15-methyl P
GF2a
11%9%
30%
2%
45%
2%
Overview
• Prostaglandins (PGs) and Thromboxanes (TXs)• NSAIDs• Gout
NSAIDs
• COX 1, COX 2 and COX3• COX 1/COX 2 IC50 ratios• COX 1 and COX 2 inhibitor side effects• Cancer• Structural Classes of NSAIDs
NSAIDs will inhibit [blank] in a patient
A. COX 1B. COX 2C. COX 3D. COX 1 and COX 2E. COX 1, COX 2 and
COX 3
COX 1COX 2
COX 3
COX 1 and COX 2
COX 1, COX 2 and COX 3
0% 0%
13%
87%
0%
COX 3 should be considered with NSAID therapeutic regiments.
A. TrueB. False
TrueFa
lse
93%
7%
COX 1 has a larger active site than COX 2.
A. TrueB. False
TrueFa
lse
43%
57%
NSAIDs
• COX 1, COX 2 and COX3• COX 1/COX 2 IC50 ratios• COX 1 and COX 2 inhibitor side effects• Cancer• Structural Classes of NSAIDs
A new COX inhibitor has a COX-1/COX-2 IC50 ratio of 0.1. What COX enzyme is it selective for?
A. COX-1B. COX-2C. Non-specificD. COX-3
COX-1COX-2
Non-specifi
cCOX-3
58%
0%2%
40%
NSAIDs
• COX 1, COX 2 and COX3• COX 1/COX 2 IC50 ratios• COX 1 and COX 2 inhibitor side effects• Cancer• Structural Classes of NSAIDs
Inhibition of PG leads to all but the following in the GI tract
A. Increase HCO3B. Increase in H+C. Increase in mucusD. Decrease in mucusE. A and BF. B and CG. A and C
Increase
HCO3
Increase
in H+
Increase
in m
ucus
Decrease
in m
ucus
A and B
B and C
A and C
9%
0%
9%
59%
5%5%
14%
What are not COX 1 side effects
A. GI bleedingB. HypotensionC. Clotting disordersD. BronchodilationE. A and BF. B and CG. B and D
GI bleeding
Hypotension
Clotting d
isord
ers
Bronchodila
tion
A and B
B and C
B and D
0%
11%
2%
48%
25%
7%7%
PG inhibition leads to bronchoconstriction through
A. PGE2B. PGE1C. PGG2D. Leukotrienes (LT)E. TXA2
PGE2PGE1
PGG2
Leukotri
enes (LT)
TXA2
7% 5% 5%
82%
2%
What type of adverse side effects do you anticipate by interfering with renin-angiotensin system through COX-2
inhibition?
A. HypertensionB. Hypertension and
Renal FailureC. Renal FailureD. Brain DamageE. None of the above
Hypertensio
n
Hypertensio
n and Renal F..
.
Renal Failu
re
Brain Damage
None of the ab
ove
2%
76%
0%0%
22%
NSAIDs
• COX 1, COX 2 and COX3• COX 1/COX 2 IC50 ratios• COX 1 and COX 2 inhibitor side effects• Cancer• Structural Classes of NSAIDs
What are non COX 2 functions for NSAIDs in Cancer cells?
A. Block NF-kappaB signaling
B. Activate Peroxisome proliferator receptor
C. Increase ApoptosisD. Activate NF-kappaB
signalingE. A, B and CF. All the above
Block NF-kappaB sig
naling
Activa
te Peroxisome prol...
Increase
Apoptosis
Activa
te NF-kappaB sig
n...
A, B and C
All the above
0% 0%
14%
71%
0%
14%
Which drug is non-selective for COX 1 and COX 2
A. Low dose AspirinB. High dose AspirinC. IbuprofenD. CelecoxibE. All the aboveF. B and C
Low dose
Aspirin
High dose Aspirin
Ibuprofen
Celecoxib
All the above
B and C
2%7%
68%
0%0%
23%
What is not a structural class of NSAIDs?
A. SalicylatesB. ProfensC. FenacsD. OxicamsE. Statins
Salicy
lates
Profens
Fenacs
Oxicams
Statins
7%2%
89%
0%2%
Salicylates inhibit by the following mechanisms
A. CompetitiveB. IrreversibleC. Non-competitiveD. UncompetitiveE. A and BF. B and CG. All the above
Competitive
Irreve
rsible
Non-competitive
Uncompetitive
A and B
B and C
All the above
2%
7%5% 5%
26%
56%
0%
How does low dose Aspirin prevent stroke and heart attack?
A. reduce PGE2 B. reduce PGI2
C. reduce TXA2
D. B and CE. A, B and C
reduce PGE2
reduce PGI2
reduce TXA2
B and C
A, B and C
0% 0%
11%
41%
48%
Oxicams are acidic by which mechanism
A. ReductionB. OxidationC. HydrolysisD. Keto-enol
tautomerism
Reduction
Oxidation
Hydrolysis
Keto-enol tautomeris
m
5%
44%
7%
44%
What coxib is available in U.S. markets?
A. LumiracoxibB. EtoricoxibC. RofecoxibD. CelecoxibE. ValdecoxibF. None of the above
Lumira
coxib
Etoricoxib
Rofecoxib
Celecoxib
Valdecoxib
None of the ab
ove
0% 0% 0%0%
98%
2%
Overview
• Prostaglandins (PGs) and Thromboxanes (TXs)• NSAIDs• Gout
What is not a strategy for treating gout?
A. Decrease inflammation
B. Increase Uric Acid Reabsorption
C. Inhibit Uric Acid synthesis
D. None of the above
Decrease
inflammation
Increase
Uric Acid
Reabs...
Inhibit Uric
Acid sy
nthesis
None of the ab
ove
0%
35%
2%
63%
The molecule below is?
A. Uric AcidB. AllopurinolC. XanthineD. HypoxanthineE. Allopurinol
Uric Acid
Allopurin
ol
Xanthine
Hypoxanthine
Allopurin
ol
5%
21%
7%
47%
21%
Colchicine is metabolized by
A. CYP1A2B. CYP2C9C. CYP3A4D. UGTsE. B and DF. C and D
CYP1A2
CYP2C9
CYP3A4UGTs
B and D
C and D
4%
16%
22%24%
9%
24%
Why is it bad to take allopurinol or febuxostat with XO ligands?
A. Increase blood plasma XO ligand concentration and toxicity
B. Decrease blood plasma XO ligand concentration and increased XO ligand toxicity
C. No effect on blood plasma XO ligand concentration or toxicity
D. None of the above
Increase
blood plasma XO...
Decrease
blood plasma XO...
No effect on blood plas..
None of the ab
ove
78%
0%0%
23%
Good Luck on the Test: Questions