Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm Block 2 > 2 - Eicosanoids > Flashcards

2 - Eicosanoids Flashcards

1
Q

In humans, what is the most abundant precursor of eicosanoids?

A

Arachidonic acid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the biosynthesis of eicosanoids?

A

Release of arachidonic acid (R2) from phosphatidyl inositol by phospholipase A2 (PLA2)

Calcium dependent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Glucocorticoids induce ________ which suppresses PLA2 activity. What is the result of this?

A

annexin-1 (lipocortin)

This means that you won’t cleave arachidonic acid off of phosphatidyl inositol and you can’t make eicosanoids. This is how glucocorticoids have an anti-inflamm response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How are prostaglandins and thromboxanes synthesized?

A

Cyclooxygenase: two isoforms - COX1 and COX2
-2 distinct activities at two distinct active sites on both proteins

Both isoforms can:

  • oxygenate and cyclize free arachidonic acid to form PGG2
  • use peroxidase activity to reduce PGG2 to PGH2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the main differences between COX1 and COX2 isoforms?

A

COX1 is constituitive and is expressed in all tissues.

COX2 is inducible and has a promoter region that binds TFs and is commonly seen in inflammation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the fate of Prostaglandin H2 (PGH2)?

A

They are made into prostaglandins and thromboxane via cyclooxygenases (COX).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the difference between PGE2 and PGE1?

A

Nothing, the number just describes the number of double bonds in the molecule.

Four our purposes they have the same activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are leukotrienes made? What activates this?

A

From arachidonic acid via 5-lipoxygeanase (5-LOX).

FLAP - 5 lipoxygenase activating protein activates it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

5-Lipoxygenase (5-LOX) turns arachidonic acid into _____. Then what happens?

A

Into LTA4, which can be made into:

  • LTB4 via LTA4 hydrolase
  • LTE4 via LTC4 synthase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the function of LTB4?

What is the function of LTE4?

A

LTB4: neutrophil chemotaxis, inflammation, and mucus production.

LTE4: allergy, bronchoconstriction. and mucus production.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What drug inhibits 5-lipoxygenase (5-LOX), resulting in no production of any leukotrienes? What is this drug used to treat?

A

Zileuton

Prophylaxis and treatment of chronic asthma; not appropriate for reversal of bronchospasm in acute asthma attacks.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What drugs inhibit the production of LTD4, a molecule in the pathway to make LTE4?

A

Montelukast, Zafirkulast, and pranulukast.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What drug is a cysteinyl leukotriene receptor antagonist with no effect on LTB4? What is the therapeutic use of this drug?

A

Zafirlukast.

It does NOT inhibit biosynthesis, it works by blocking the receptor.

Prophylaxis and chronic treatment of asthma; not appropriate for reversal of bronchospasm in acute asthma attacks.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What effects do leukotrienes have on inflammation? Which receptors are associated with each symptom? What is associated with increased levels of leukotrienes.

A

Increased vascular permeability and bronchoconstriction: LTC4 and LTD4

Chemoattractant for PMNs: LTB4

Increased in allergies/asthma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How are eicosanoids metabolized? Why is this important to know?

A

They are rapidly metabolized

Hard to use clinically unless you modify the drug to increase the half-life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do prostaglandins and thromboxanes act?

A

By interacting with a specific GPCR and causing the release of a second messenger.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the biological actions of PGE2 through its four receptors: EP1, EP2, EP3, and EP4?

A

EP1: Gq increases Ca2+ (PKC)

EP2: Gs to increases cAMP. (PKA)

EP3: can work through Gq to increase Ca2+ and Gi to increase Ca2+ and decrease cAMP.

EP4: Gs to increase cAMP (PKA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the function of Leukotriene receptors?

A

LTB4: chemotaxis

LTC4, LTD4, and LTE4 cause bronchoconstriction and increase vascular permeability.

Effector system increases intracellular calcium.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What cells can form eicosanoids?

A

Virtually every cell in the body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the action and function of PGE2 and PGI2 in the periphery?

A

Act through specific GPCRs and sensitize pain receptors by lowering the threshold of nociceptors of C fibers.

Cause hyperalgesia and potentiate the pain-producing activity of mediators like bradykinin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Do PGs alone cause pain?

A

Only in high concentrations.

Their main action is to decrease the threshold for pain so lower concentrations of other mediators are needed to activate pain fibers.

22
Q

What is the sequence of events that occurs with fever?

A
  1. Increased formation of cytokines.
  2. Increased synthesis of PGE2 in areas of the brain associated with temperature control
  3. increased cAMP and triggers hypothalamus to elevate body temp
  4. Hypothalamus regulates the set point at which body temperature is maintained = fever
23
Q

What induces platelet aggregation and how is it made?

A

TXA2 (thromboxane)

Activation of platelet membrane PLA2 causes release of arachidonic acid, which is made into PGH2 via COX-1.

Then PGH2 made into TXA2 via TXA synthase.

24
Q

What is the function of PGI2 and how is it made?

A

Inhibits platelet aggregation and causes vasodilation by increasing cAMP.

Arachidonic acid made by endothelial cells (NOT platelets), converted to PGH2 via COX1 or COX2.

PGH2 made into PGI2 via PGI synthase.

25
Q

What role does PGE2 play in reproduction and parturition? What receptors are involved?

A

Initiation and progression of labor.

Induces uterine contractility through EP1 and EP3 mediated increase in calcium.

Cervical ripening via EP2 and EP4 mediated increase in cAMP.

26
Q

What mediator causes contractions of the uterus during labor through an increase in calcium?

A

PGF2alpha.

27
Q

What role does PGF2alpha play in the non-pregnant uterus?

A

Contributes to symptoms of primary dysmenorrhea (cramping)

28
Q

Which mediators cause vasodilation? What about vasocontriction? Which can act as both?

A

Vasodilation: PGE2 and PGI2

Vasocontriction: TXA2 and PGF2alpha.

*In some cases, PGE2 can act as a vasoconstrictor when it reactors with the receptor EP1/EP3 to increase calcium and inhibit cAMP.

29
Q

Which mediators increase renal blood flow and promote diuresis and natriuresis? What mediator may be important in kidney disease,COX1 or COX2?

A

PGE2 and PGI2.

COX2 may be more important in kidney disease than COX1.

30
Q

What is the major PG that affects tone in the ductus arteriosus?

A

PGE2.

Causes relaxation and is developmentally regulated for loss of responsiveness in neonate compared to fetus.

31
Q

Leukotrienes cause _____ and ______.

A

Bronchoconstriction through contraction of pulmonary smooth muscle.

Chemotaxis.

32
Q

What mediators play a role in GI secretion?

A

COX1 is important in the synthesis of cytoprotective PGs.

PGE2 (EP3) and PGI2 (IP) inhibit gastric acid secretion.

33
Q

_______ have a cytoprotective effect that suppresses gastric ulceration.

A

Prostaglandins (PGs)

34
Q

What is the therapeutic use of prostaglandins? How have we combatted this issue?

A

Limited due to short half-life in circulation and have significant adverse effects.

Have developed analogs with structures that prevent metabolism for 15-OH dehydrogenase and 13-PG reductase.

35
Q

What drug causes cervical ripening in pregnancy, relaxes cervical smooth muscle, and works through a EP4 receptor to increase cAMP? What are the adverse effects of this drug? How it is given and how much is given?

A

Dinoprostone/PGE2

Given via cervical gel, 0.5 mg max.

Can cause uterine rupture

36
Q

What is a second use of Dinoprostone/PGE2 besides cervical ripening in pregnancy? How is it given and how much is given?

A

Termination of early pregnancy through uterine contractions via EP1/EP3 receptors and an increase in calcium.

Vaginal suppository, 20 mg (max 240).

Can cause uterine rupture.

37
Q

What drug can be used for termination of early pregnancy via uterine contraction at FP through increased calcium but can also be used to control postpartum hemorrhage?

A

Carboprost/PGF2alpha.

Termination of pregnancy: intramuscular (250 micrograms < 12 mg)

Control of hemorrhage: when conventional treatments fail. Intramuscular (250 micrograms <2 mg)

38
Q

What are the adverse effects of Carboprost/PGF2alpha that occur with both of it’s uses?

A

Uterine rupture, Gi-related symptoms such as nausea and vomiting.

39
Q

What drug suppresses gastric acid secretion by stimulating EP3 on parietal cells and a decrease in cAMP? What is a clinically important about who to give this to?

A

Misoprostol/PGE1 analog.

Contraindicated in pregnancy because it also acts on EP3 receptors elsewhere, such as the uterus and can cause contraction (ie termination of pregnancy).

40
Q

When is misoprostol/PGE1 analog used therapeutically? How is it given?

A

Used as a replacement therapy for prevention of ulcers caused by long-term administration of NSAIDs.

Given 4x a day orally.

41
Q

What drug is used therapeutically to treat impotence/erectile dysfunction and temporary maintenance of patent ductus arteriosus until surgical correction?

A

Alprostadil/PGE1.

42
Q

How does alprostadil/PGE1 treat erectile dysfunction? What receptors does it work on? What second messenger is involved? How is it given?

A

Relaxation of trabecular smooth muscle and dilation of cavernosal arteries, leading to blood entrapment.

EP2 and EP4 receptors, Increases cAMP.

Given via an intracavernous injection.

43
Q

What is the mechanism by which alprostadil/PGE1 maintains a patent ductus arteriosus? How is it given?

A

EP2/EP4 receptors, cAMP mediated relaxation of ductus arteriosus smooth muscle.

IV infusion.

44
Q

What drug is used to treat idiopathic pulmonary arterial hypertension? How does it do this? What drugs can it interact with?

A

Epoprostenol/PGI2

IP receptor, causes cAMP mediated dilation of pulmonary artery vascular smooth muscle.

Can interact with anti-hypertensive therapy or anti-platelet therapy.

45
Q

What drug works through a novel prostamide receptor to treat glaucoma? How is it given? What are side effects?

A

Bimatoprost/prostamideF2alpha

Given via an ophthalmic solution, can cause redness, itching, changes in eye color, and increase length and number of eyelashes.

46
Q

What is a second therapeutic use for bimatoprost/prostamideF2alpha? What are some adverse effects?

A

(Latisse)

Eyelash hypotrichosis

Excess, unwanted hair growth, brown iris pigmentation, eye itching/redness.

47
Q

What drug can inhibit leukotriene-induced chemotaxis AND bronchoconstriction?

A

Zileuton.

48
Q

Are all prostaglandins vasodilators?

A

NO.

49
Q

What is the MAJOR therapeutic use of epoprostenol?

A

Primary pulmonary hypertension (Not just just HTN).

50
Q

What is the MAJOR therapeutic use for alprostadil?

A

Impotence

Maintenance of patent ductus arteriosus.

51
Q

What is the MAJOR therapeutic use of misoprostol?

A

NSAID-induced ulcer (not just ulcer).

52
Q

Do prostaglandins regulate systemic blood pressure? Describe how they regulate blood pressure?

A

No! They only regulate LOCAL blood pressure by acting as a vasodilator.

They can counteract the effects of vasoconstrictive compounds such as angiotensin 2 in the kidney in order to maintain blood flow.

They also increase Na+ and H2O excretion.

Pharm Block 2 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions