Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology Block 2 > 02 Eicosanoids > Flashcards

02 Eicosanoids Flashcards

1
Q

What is the precursor of eicosanoids?

A

Arachidonic acid

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

What families fall under eicosanoids?

A

Derived from 20C essential FA with 3, 4, or 5 double bonds

Prostaglandins and Leukotrienes

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

How is arachidonic acid found in the cell?

A

Free AA in cells is very low; found esterfied to membrane phospholipids.

Phospholipase A2 (Ca2+ dept.) hydrolyzes bond and releases AA

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

Phospholipase A2

A

(Ca2+ dept.) hydrolyzes bond and releases Arachidonic Acid

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

What enzyme makes prostaglandin from arachidonic acid?

A

Cyclooxygenases (COX-1 and COX-2)

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

Cyclooxygenase

A

Oxygenates and cyclizes the precursor FA to form cyclic endoperoxide PGG2

Peroxidase activity reduces PGG2 to PGH2

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

How are COX-1 and COX-2 similar?

A

Heme protein
Dimer of 70 kDa
Membrane bound: ER and Nuclear envelope

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

Who has a bigger more accessible active site, COX-1 or COX-2?

A

COX-2

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

What is the difference between COX-1 and COX-2

A

Encoded on different chromosomes

COX-1: Constitutive
– expressed in all tissues

COX-2: Inducible

    • promoter region that binds transcription factors
    • seen with inflammation: NFkB, MAPK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the fate of PGH2?

A

Transformed enzymatically into:

  • TXA2
  • PGF2alpha
  • PGE2 or PGE1 (double bonds)
  • PGI2
  • PGD2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which is constitutive and Inducible between COX-1 and COX-2?

A

COX-1: Constitutive
– expressed in all tissues

COX-2: Inducible

    • promoter region that binds transcription factors
    • seen with inflammation: NFkB, MAPK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are Leukotrienes synthesized?

A

5-Lipoxygenase (5-LOX)

Catalyzes oxygenation of FA to lipid hydroperoxides

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

What is the difference of inhibition of COX-1 and COX-2 between NSAIDs vs Glucocorticoids?

A

NSAIDS inhibit COX-1 and COX-2

Glucocorticoids decrease expression of COX-2 but not COX-1

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

What decreases the expression of COX-2 but not COX-1?

A

Glucocorticoids

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

Inhibitor of 5-lipoxygenase

A

Zileuton

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

Zileuton

A

Pharm: T 1/2 = 2.5 hrs; metab by CYPs

Mech: Inhibitor of 5-lipoxygenase = No LT production

  • cys-LTs (bronchoconstriction and increase vascular permeability)
  • LTB4 (chemotaxis)

AE: some inc liver enzymes

Tx: Prophylactic tx of mild chronic asthma

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

What can be used for prophylactic treatment of mild chronic asthma?

A

Zileuton (inhibitor of 5-lipoxygenase) or Zafirlukast Iinhibits cys-LTs)

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

What inhibits cys-LTs for bronchoconstriction and increased vascular permeability as well as LTB4 (chemotaxis)?

A

Zileuton (inhibitor of 5-lipoxygenase)

Zafirlukast (Cysteinyl leukotriene receptor antagonist)

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

What is a cysteinyl leukotriene receptor antagonist?

A

Zafirlukast

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

Zafirlukast

A

Pharm: T 1/2 = 10 hrs, metab by CYP2C9

Mech: Cysteinyl leukotriene receptor antagonist

AE: minimal

Tx: Prophylactic tx of mild chronic asthma

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

Which has a longer duration of action, Zileuton or Zafirlukast?

A

T 1/2:
Zafirlukast = 10 hrs
Zileuton = 2.5 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where is 95% of PGE1 inactivated?

A

95% inactivated in one passage through pulmonary circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Eicosanoid catabolism

A
  1. Oxidation of the 15-OH group to ketone by 15-OH PG dehydrogenase
    followed by reduction catalyzed by Δ13 PG -reductase
    (initial step; rapid; most biological activity lost)
  2. β and ω oxidation of side chains giving a polar compound that is excreted
    (second step; relatively slow)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Cellular Mechanism of Action of Prostaglandins

A

wide diversity of effects explained by a number of distinct receptors coupled to effector mechanisms through G proteins leading to either Ca2+ mobilization or inc cAMP resulting in inflammation, pain, immunoregulation, mitogenesis, plasticity, and cell injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Cellular Mechanism of Action of Leukotrienes

A

G protein coupled receptors:

– LTB4
• BLT1 and BLT2
• chemotaxis

– LTC4 & LTD4 & LTE4
• cysLT1 and cys LT2
• Bronchoconstriction
• Increase vascular permeability

Effector system:
– Increase intracellular calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What leukotriene receptor results in chemotaxis?

A

LTB4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What leukotriene receptors are associated with cys-LTs, bronchoconstriction, mucus production, and increased vascular permeability?

A

LTC4, LTD4, LTE4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
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
29
Q

PGE2 and PGI2 located in the periphery result in?

A
  • Sensitize pain receptors to mechanical and chemical stimulation
  • Lower threshold of nociceptors of C fibers
  • Hyperalgesia
  • Potentiate pain, producing activity of other mediators like bradykinin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

PGs located in CNS result in?

A

Expression of COX-2 in spinal cord increased in inflammation

Centrally generated PGE2 may contribute to neuropathic pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Do PGs alone cause pain?

A

ONLY in high concentrations

In injury, PGs decreases the THRESHOLD for pain so that lower concentrations of other mediators (histamine, bradykinin, substance P) can activate the pain fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the steps to fever formation?

A
  1. Increased formation of cytokines (IL-1, TNF-alpha) in circulation
  2. Increased synthesis of PGE2 at hypothalamus via COX-2
  3. PGE2 increases cAMP, which triggers hypothalamus to elevate body temperature thermorergulatory set point
  4. Heat conservation/production => fever

Hypothalamus regulates the set point at which body temperature is maintained

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What controls body temp? What factors result in fever?

A

Increased PGE2 via COX-2 at hypothalamus increases cAMP which triggers hypothalamus to elevate body temp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How is thromboxane synthesized?

A

Activation of platelet membrane PLA2 causes release of arachidonic acid and converted to thromboxane by COX-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Function of thromboxane

A

TXA2 induces platelet aggregation

Acts of TP receptor
Inc in intracellular Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What induces platelet aggregation?

A

Thromboxane (TXA2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Activation of endothelial membrane PLA2 results in?

A

Release of arachidonic acid and its metabolism to PGI2 by COX-1 and COX-2 to inhibit platelet aggregation and to also vasodilate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Activation of platelet membrane PLA2 results in?

A

release of arachidonic acid and converted to thromboxane by COX-1

39
Q

How is PGI2 synthesized?

A

Activation of endothelial membrane PLA2 releases arachidonic acid and its metabolism to PGI2 by COX-1 and COX-2

40
Q

Function of PGI2

A

ENDOTHELIUM

Inhibits platelet aggregation

  • stimulation of IP receptors
  • inc in cAMP

Vasodilation

  • stimulation of IP receptors
  • inc in cAMP
41
Q

What PG inhibits platelet aggregation and causes vasodilation of endothelium?

A

PGI2

42
Q

Pregnancy induces the increase in what enzymes?

A

COX-1 and COX-2

43
Q

PGI2 effect on uterus?

A

Early pregnancy:

  • keeps uterus in quiescent state
  • relaxation via IP and increase cAMP
44
Q

What PG is associated with early pregnancy and keeping the uterus in quiescent state?

A

PGI2

45
Q

PGE2 effect on uterus?

A
  • Initiation and progression of labor
  • At EP1/EP3 receptors, induces uterine contractility (increases Ca2+)
  • At EP2/EP4 receptors, mediates cervical ripening (increases cAMP)
46
Q

What PG is associated with the initiation and progression of labor (induces uterine contractility AND cervical ripening)?

A

PGE2
- At EP1/EP3 receptors, induces uterine contractility (increases Ca2+)

  • At EP2/EP4 receptors, mediates cervical ripening (increases cAMP)
47
Q

PGF2-alpha effect on pregnant uterus?

A

Contracts uterus during labor (inc Ca2+)

48
Q

Primary Dysmenorrhea

A

menstrual pain severe enough to limit normal activities and require medication in the presence of normal pelvic organs

In menstruation, disruption of uterine membranes causes release of AA and increase PGF2-alpha syn (COX1 and COX2)

  • contract uterus
  • contract GI smooth muscle
  • sensitize afferent pain fibers
49
Q

Effect of PGF2-alpha on non-pregnant uterus?

A

Primary Dysmenorrhea– menstrual pain severe enough to limit normal activities and require medication in the presence of normal pelvic organs

concentrations increase in menstrual fluid and cause vasoconstriction, uterine contraction, pain

50
Q

Systemic blood pressure generally falls in response to what PG?

A

PGE2 at EP2/EP4 receptors

PGI2

51
Q

There is profound hypotension after IV administration of what PG?

A

PGI2

52
Q

What PGs are predominantly vasodilators?

A

PGE2 at EP2/EP4 receptors
PGI2
PGD2 (except in pulmonary, where it is a constrictor)

53
Q

What PG is a (potent) vasoconstrictor?

A

TXA2 (potent)
PGF2-alpha (not potent)
PGD2 (only pulmonary)

PGE2 at EP1/EP3 receptors

54
Q

Why is it important to know locally produced vasodilator PGs counteract effects of circulating vasoconstrictor autocoids (angiotensin II)?

A

To maintain blood flow to vital organs like the kidney

55
Q

What maintains blood flow to vital organs like the kidney?

A

Locally produced vasodilator PG counteracting the effect of circulating vasoconstrictor autocoids (angiotensin II)

56
Q

What is the role of PGs on the fetal heart?

A

PGs maintain patency of ductus arteriosus (allows most blood leaving RV to bypass pulmonary circulating and pass into the descending aorta)

PGE2 affects tone
- relaxation via EP4 receptor

57
Q

What PG plays a major role in maintaining the ductus arteriosus?

A

PGE2 affects tone

- relaxation via EP4 receptor

58
Q

What causes the loss of fetal ductus arteriosus?

A
  • loss of placenta (major source of PGE2 in fetus)
  • dec in PGE2 receptors (EP4 = dilator)
  • inc pulmonary blood flow (major site for PG catabolism)
59
Q

When sensitized lung tissue is challenged by an antigen (allergic reaction), what happens?

A

Releases of prostaglandins and Leukotrienes

PGE2 and PGI2 = relax
PGF2-alpha, PGD2, TXA2 = constrict
LTC4 and LTD4 = constrict

Bronchoconstrictor response to leukotrienes predominates

60
Q

What PGs are associated with bronchial relaxation?

A

PGE2 and PGI2

61
Q

What chemicals are associated with bronchoconstriction?

A

PGF2-alpha, PGD2, TXA2

LTC4 and LTD4
- predominates over PGs that relax lung

62
Q

What PGs increase renal blood flow and promote diuresis and natriuresis?

A

PGE2 and PGI2

63
Q

What is the effect of PGE2 and PGI2 on the kidney?

A

increase renal blood flow and promote diuresis and natriuresis

64
Q

In the GI, what synthesizes cytoprotective PGs to suppress gastric ulceration?

A

COX-1

65
Q

What is the effect of PGI2 on GI?

A

Inhibit gastric acid secretion

Increase gastric mucosal blood flow

66
Q

What PGs inhibit gastric acid secretion and increase gastric mucosal blood flow?

A

PGE2 at EP3 and PGI2

67
Q

What is the effect of PGE2 on GI?

A 
Inhibit gastric acid secretion (EP3)
Increase gastric mucosal blood flow (EP2/EP4)
Stimulate release of viscous mucus
Stimulate bicarbonate secretion
Contract GI smooth muscle (EP1)

==> Suppress gastric ulceration

68
Q

What enzyme mediates the inflammatory and immune response?

A

COX-2

PGs and Leukotrienes released by a number of mechanical, thermal, chemical, bacterial insults

69
Q

What do PGs contribute to the inflammatory/immune response?

A

Signs and symptoms of inflammation (fever, pain, vasoactive effects)

PGE2/PGI2:

  • directly inc blood flow
  • indirectly enhance edema formation and leukocyte infiltration
70
Q

What do Leukotrienes contribute to the inflammatory/immune response?

A

LTC4 and LTD4 = increased vascular permeability

LTB4 = chemoattractant for neutrophils

71
Q

In what cancers would you find an increased concentration of PGs?

A

Colon, Breast, Renal cell adenocarcinoma

  • PGs induce cellular proliferation
  • Induced COX-2
72
Q

Why is the use of PGs as therapeutic agents limited?

A

Significant AEs

Short t 1/2 in circulation

73
Q

Dinoprostone

A

Synthetic PGE2 analog

  1. Cervical ripening in pregnancy (EP4 receptor)

Mech: Collagenase activation and relaxation of cervical smooth muscle

  1. Abortion of early pregnancy (EP1/EP3 receptor)

Mech: Uterine contractions

AE:

  • GI: n/v/d
  • fever
  • uterine rupture (contraindicated w/ hx of C-section or uterine sx)
74
Q

What drug is a synthetic analog of PGE2?

A

Dinoprostone

75
Q

What drug is used for cervical ripening or termination of early pregnancy?

A

Dinoprostone (PGE2)

  1. Cervical ripening in pregnancy (EP4 receptor)
  2. Abortion of early pregnancy (EP1/EP3 receptor)
76
Q

Carboprost Tromethamine

A

PGF2-alpha analog; longer half life (mins)

  1. Pregnancy termination during 2nd trimester

Mech: Stimulates uterine contractility by FP receptors

  1. Control postpartum hemorrhage

Mech: Post partum, causes myometrial contractions via FP receptors. Hemostasis at site of placenta formation.

AEs:

  • GI: n/v/d
  • fever
  • uterine rupture (contraindicated w/ hx of C-section or uterine sx)
  • bronchoconstriction (rare)
77
Q

What drug is a PGF2-alpha analog?

A

Carboprost Tromethamine

Bimatoprost

78
Q

What drug is used for termination of pregnancy during second trimester?

A

Carboprost Tromethamine (PGF2-alpha)

79
Q

What drug is used to control postpartum hemorrhage?

A

Carboprost Tromethamine (PGF2-alpha)

80
Q

Misoprostol

A

PGE1 analog

Replacement therapy for prevention of ulcers due to long term NSAID use (4x/day)

Mech:

  • suppress gastric acid secretion by parietal cells (EP3 receptors)
  • dec in cAMP
  • inc mucin and bicarb secretion
  • inc mucosal blood flow

AEs:

  • diarrhea (common)
  • contraindicated in pregnancy
81
Q

What drugs are PGE1 analogs?

A

Misoprostol

Alprostadil

82
Q

What drug is used as replacement therapy for NSAID induced ulcers?

A

Misoprostol (PGE1 analog)

83
Q

What are the AEs of misoprostol?

A

Diarrhea (common)

Contraindicated in pregnancy

84
Q

Alprostadil

A

PGE1

  1. Impotence/Erectile Dysfunction (Injection)

Mech: inc cAMP relaxes smooth muscle of corpus cavernosum (EP2/EP4 receptors)

AE:

  • pain at site of injection
  • priapism: prolonged erection
  1. Maintenance of patent ductus arteriosus (IV)

Mech: cAMP-mediated relaxation of ductus arteriosus smooth muscle (EP2/EP4 receptors)

AE:
- apnea in 10% neonates; <2 kg

85
Q

What PG drug is used to treat erectile dysfunction? What is potential AE?

A

Alprostadil (PGE1)

Can cause priapism (prolonged erection)

86
Q

What PG drug is used to maintain a patent ductus arteriosus?

A

Alprostadil (PGE1)

87
Q

Epoprostenol

A

PGI2

Tx: Primary pulmonary hypertension which leads to right heart failure

  • rare Female idiopathic disease
  • continuous IV

Mech: cAMP-mediated dilation of pulmonary artery vascular smooth muscle

AE:

  • n/v
  • headache
  • flushing
  • potential drug interactions
88
Q

What drug is PGI2?

A

Epoprostenol

89
Q

What drug is administered as a continuous IV to treat primary pulmonary hypertension?

A

Epoprostenol (PGI2)

90
Q

Bimatoprost

A

PGF2-alpha

  1. Glaucoma (OPH)

Mech: inc outflow of aqueous humor

AE:

  • eye redness, itching, increased brown pigment
  • may inc length and number of eyelashes
  1. Eyelash hypotrichosis (OPH)

Mech: inc percent and duration of hairs in growth phase

AE:
- excess, unwanted hair growth, brown iris pigmentation, eye redness, itching

91
Q

What therapeutic PG is used to treat glaucoma?

A

Bimatoprost (PGF2-alpha)

92
Q

What drug is used to treat eyelash hypotrichosis?

A

Bimatoprost (PGF2-alpha)

93
Q

What drug can result in AEs of excess/unwanted hair growth, brown iris pigmentation, eye redness and itching?

A

Bimatoprost (PGF2-alpha)

Pharmacology Block 2 (12 decks)

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