review for the test

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