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

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What Prostaglandin is this?

A. PGE1B. PGE2C. PGF2alphaD. PGG2E. PGH2F. PGI2G. TXA2

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What Prostaglandin is this?A. PGE1B. PGE2C. PGF2alphaD. PGG2E. PGH2F. PGI2G. TXA2

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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

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PG and TXs

• Structures• Functions• Signaling• Transport• Synthesis and Degradation• PG as drugs

Prostaglandin signaling within the cell is?

A. EndocrineB. AutocrineC. ParacrineD. Intracrine

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What are not involved in Prostaglandin and Thromboxane signaling

A. Plasma membrane bound GPCRs

B. Nuclear membrane bound GPCRs

C. Nuclear ReceptorsD. OATP transporter

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Prostaglandin E2 (PGE2) binds to what type of receptor

A. DP1B. EP1C. FPD. IPE. TP

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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

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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

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The product of COX 2 is?

A. Arachidonic AcidB. PGE1C. PGE2D. PGF2alphaE. PGG2F. PGH2G. PGI2H. TXA2

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What is not a mechanism of metabolism for PG?

A. alpha-oxidation B. beta-oxidationC. omega-oxidationD. reductionE. alcohol

dehydrogenation

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How is TXB2 produced

A. reductionB. oxidationC. hydrolysis D. conjugation

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Which Cytochrome P450 (CYP) is involved in w-oxidation?

A. CYP1A1B. CYP2C9C. CYP3A4D. CYP4A

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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

diclofenac:10

What prostaglandin is Aprostadil?A. PGE1

B. PGE2

C. TXA2

D. Prostacyclin onlyE. PGI2 onlyF. Prostacyclin and PGI2

Aprostadil:10

What is not a use of Aprostadil

A. Erectile dysfunctionB. Congenital hear

defectC. HypertensionD. Induce laborE. A and BF. C and D

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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

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What are not formulations of Alprostadil?

A. IV injectionB. Penile injectionC. OralD. Urethral

Suppository

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What are ADR of Alprostadil?

A. Pain/RashB. Light HeadedC. Bleeding and

BruisingD. Flu SymptomsE. All the above

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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

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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

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COX 3 should be considered with NSAID therapeutic regiments.

A. TrueB. False

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COX 1 has a larger active site than COX 2.

A. TrueB. False

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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

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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

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What are not COX 1 side effects

A. GI bleedingB. HypotensionC. Clotting disordersD. BronchodilationE. A and BF. B and CG. B and D

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PG inhibition leads to bronchoconstriction through

A. PGE2B. PGE1C. PGG2D. Leukotrienes (LT)E. TXA2

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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

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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

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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

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What is not a structural class of NSAIDs?

A. SalicylatesB. ProfensC. FenacsD. OxicamsE. Statins

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Salicylates inhibit by the following mechanisms

A. CompetitiveB. IrreversibleC. Non-competitiveD. UncompetitiveE. A and BF. B and CG. All the above

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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

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Oxicams are acidic by which mechanism

A. ReductionB. OxidationC. HydrolysisD. Keto-enol

tautomerism

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What coxib is available in U.S. markets?

A. LumiracoxibB. EtoricoxibC. RofecoxibD. CelecoxibE. ValdecoxibF. None of the above

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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

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The molecule below is?

A. Uric AcidB. AllopurinolC. XanthineD. HypoxanthineE. Allopurinol

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Colchicine is metabolized by

A. CYP1A2B. CYP2C9C. CYP3A4D. UGTsE. B and DF. C and D

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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

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Good Luck on the Test: Questions