Brainscape's Knowledge GenomeTM

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


See full index

MSK exam 1 > autacoids eicosanoids > Flashcards

autacoids eicosanoids Flashcards

1
Q

what are the lipid derived eicosanoids

A

prostaglandins
thromboxanes
leukotrienes

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

eicosanoid basic facts

A

lipid mediators from 20 carbon essential polyunsaturated fatty acids
cant make de novo
most come from arachidonic acid (not free, esterified to SN2 position)

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

cell membrane phospholipids to arachidonic acid via what enzyme

A

phospholipases (PLA2)

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

arachidonic acid to isoprostanes via what enzyme

A

non-enzymatic oxidation

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

three things from arachidonic acids

A

cyclooxygenases
lipoxygenases
cytochrome p450

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

what are the two cyclooxygenases

A

COX-1 and 2

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

COX1 and 2 go to

A

PGG2 then to PGH2

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

PGH2 forms

A

prostaglandins (PGD2, PGE2, PGF2a)
prostacyclins (PG12)
thromboxanes (TXA2, TXB2)

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

3 lipoxygenases

A

5-LO, 12-LO, 15-LO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

5-LO forms

A

5-GETEs then LTA4

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

LTA4 forms

A

CysLTs,LTC4,D4,E4
LTB4
Lipoxins,LXA4,LXB4

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

12-LO forms

A

12-HPETEs

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

12-HPETEs forms

A

12-HETEs

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

15-LO forms

A

15-HPETEs which forms 15-HETEs

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

15-HETEs forms

A

lipoxins, LXA4, LXB4

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

cytochrome P450 forms

A

HETEs, epoxides

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

cytochrome P450 via what enzymes

A

epoxygenase and omega-hydroxylase

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

how is arachidonic acid released

A

physical, hormonal and chemical stimuli cause an influx of Ca by pertubing the cell membrane and activating phospholipase A2

rate limiting step in eicosanoid generation

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

how many reactions do COX-1 and COX-2 also called prostaglandin H synthases catalyze

A

2

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

what are the two reactions

A

oxygen-dependent cyclization of AA to PGG2

peroxidase reduction of PGG2 to PGH2

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

PGG2 and PGH2 are both what

A

potent vasoconstrictors and platelet aggregators

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

PGH2 is converted to what

A

different eicosanoid products (prostanoids) in a tissue-specific manner

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

what are the PGH2 derived prostanoids

A

PGD2, PGF2a, PGE2, TxA2, PGI2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

PGH2 in what tissue and what ezyme form PGD2

A

in brain and mast cells, and PGD2 isomerase

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

function of PGD2

A

smooth muscle contraction

inhibits platelet aggregation

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

PGH2 forms PGF2a in what tissue and what enzyme

A

in uterus and lung

PGF2a reductase

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

function of PGF2a

A

smooth muscle contraction
bronchochonstriction
abortion

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

PGH2 forms PGE2 in what tissue and what enzyme

A

macrophages and mast cells

PGE2 isomerase

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

PGE2 forms what

A

EP1,2,3,4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

function of PGE2

A 
vasodilation
hyperalgesia
fever
diuresis
immunomodulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

roles of PGE2

A

vasodilator and is responsible for cellular homeostasis
mediates vasodilatory effect of bradykinin
essential for regulation of gastric acid production

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

PGH2 forms PGI2 in what tissue and what enzyme

A

endothelium and prostacyclin synthase

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

function of PGI2

A

vasodilation

inhibits platelet aggregation

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

PGH2 forms TxA2 in what tissue and what enzyme

A

platelets and thromboxanse synthase

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

function of TxA2

A

vasoconstriction

platelet activation

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

PGI2 and TxA2 can form

A

6-keto-PGF1a
TxB2
incative form

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

formation and degradation of prostanoids

A

all are formed on demand
perform action in short time
degraded by 15-hydroxyl-PG dehydrogenases (15-OH to 15=O)

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

what are the two PGE1 analogs

A

misoprostol and alprostadil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

misoprostol

A

prophylactic for NSAID-induced gastric ulcers
low dose-cytoprotection
high dose-inhibits gastric acid production
abortion or induce labor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

alprostadil

A

maintain patency of ductus arteriosus

2nd line for erectile dysfunction by relaxing smooth muscle of corpora cavernosa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

PGF2a analog

A

latanoprost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

latanoprost

A

treatment of ocular hypertension and open-angle glaucoma by increasing outflow of aqueous humor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

arachidonic acid forms 5-HPETE via what

A

5-lipoxygenase/FLAP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

5-HPETE forms LTA4 via what

A

5-lipoxygenase/FLAP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

LTA4 forms LTB4 via

A

LTA4 hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

LTA4 forms LTC4 via

A

LTC4 synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

LTC4 forms LTD4 via

A

gamma glutamyl transpetidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

LTD4 forms LTE4 via

A

dipeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

LTC4,D4,E4 go to

A

cysteinyl leukotriene receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

LTC4,D4,E4

A

slow reacting substances of anaphylaxis
during anaphylactic reaction, secreted by mast cells to casue prolonged slow smooth muscle contraction and plays major bronchoconstrictor role in asthma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

major source of LTB4 and function

A

neutrophils (BLT1)
activation of neutrophils, margination, migration, degranulation, superoxide anion generation, eicosanoid synthesis
plasma exudation

52
Q

major source of LTC4,D4,E4 and function

A

mast cells, basophils, eosinophils

bronchoconstriction, vasoconstriction, decreased coronary blood flow, decreased cardiac contractility, plasma exudation

53
Q

arachidonic acid forms 5-HPETE via

A

5-lipoxygenase

54
Q

5-HPETE forms 5HETE which does

A

chemotaxis

55
Q

5-HPETE forms lipoxin A4 and B4 (LXA4,LXB4) via

A

12-lipoxygenase

56
Q

function of LXA4 and LXB4

A

inhibit neutrophil adhesion and chemotaxis

57
Q

selective eicosanoid inhibitors

A

COX inhibitors, LOX inhibitors, LT receptor antagonists

58
Q

COX inhibitors

A

called NSAIDs (non-steroidal anti-inflammatory drugs)

non-selective ( irreversible inhibitors (salicylates) competetive inhibitors)
COX-2 selective (-coxibs)

all except aspirin are reversible
block hydrophobic channel of COX protein where AA binds, prevents AA to PGG2
no effect on peroxidase enzyme activity

59
Q

irreversible COX inhibitors

A

salicylates include aspirin (acetylsalicycli acid) and its derivatives

aspirin acetylates serine residue of COX covalently and irreversibly inactives COX-1

aspirin switches catalytic activity of COX-2 to produce anti-inflammatory mediators

60
Q

what is aspirin used for

A

rarely for anti-inflammatory. more commonly for anti platelet aggregration

61
Q

platelets express high levels of what

A

thromboxanse synthase but not prostacyclin synthase

62
Q

vascular endothelium expresses what

A

prostacyclin synthase but no thromboxane synthase

63
Q

what does eating omega-3 fatty acids (DHA, EPA) do?

A

shifts balance towards generation of COX- and LOX-mediated anti inflammatory molecules

64
Q

DHA can use LOX to form

A

resolvin, D1,D2,D3,D4,protectin D1, maresin 1

all are anti inflammatory, promote resolution

65
Q

EPA can use LOX and COX to form

A

resolvin, E1, E2

anti-inflammatory and promote resolution

66
Q

EPA can use COX to form

A

PGG3

67
Q

PGG3 can use LOX to form

A

PGH3

68
Q

PGH3 can lead to

A

PGI3 (active)
PGE3 (less)
TXA3 (inactive)

antiinflammatory and reduce aggregation

69
Q

AA via lox forms

A

LTB4,C4,D4,E4

inflammatory, chemotaxis, bronchoconstriction

70
Q

AA via cox forms

A

PGG2

71
Q

PGG2 via cox forms

A

PGH2

72
Q

PGH2 forms

A

PGI2 (active)
PGE
TXA2(active)

inflammatory, platelet aggregation

73
Q

aspirin starts as a pro-drug and need to be biotrasnformed into what, where

A

to salicylates in the liver

80-90% are bound to plasma protein

74
Q

salicyclates are excreted where

A

through the kidney

depends on dose, and urine pH since they are organic acids (pka 3-3.5)

75
Q

low dose half time salicyclates

A

2-3hrs 1st order

76
Q

high does half time of salicyclates

A

15-30 hrs 0 order

77
Q

at high doses the liver fails to transform salicylates into what

A

salicycluric acid and phenolic glucuronide which account for 80% of excretion by the kidney

78
Q

where do metabolites of salicyclates increase

A

increase in GFP and proximal tubule secretion via reduction

79
Q

adverse effects of aspirin

A

gastroitestinal ulceration and hemorrhage
nephrotoxicity
tinnitus (ringing in the ears)

aspirin induced airway hyerpactivity

80
Q

why is there aspirin induced airway hyperactivity

A

shift in reaction from cycloocygenase to lippoxygenase pathway

81
Q

what is reye’s syndrome

A

swelling and damage to liver and brain in young children and tennagers recovering from viral infection

82
Q

how to do you treat salicyclate toxicity

A

alkaline diuresis

83
Q

clinical indications for aspirin

A

mild to moderate pain (headache, myalgia, arthalgia)

phrophylaxsis of stroke and mycocardial infarction

84
Q

contraindiccations of aspirin

A

aspirin hypersensitivity
aspirin triggered asthma
children and teenagers with chicken pox of flu due to risk if reye’s

85
Q

what to use for children and teens instead of apsirin

A

acetaminophen

86
Q

acetaminophen classification

A

as an NSAID but is not technically one

87
Q

high levels of what can render acetaminophen ineffective in inhibiting COX?

A

peroxides

88
Q

where can acetaminophen inhibit COX

A

centrally (in the brain) where peroxide levels are low

89
Q

what can acetaminophen be used for

A

analgesic and antipyretic like aspirin but not anti-inflammatory

90
Q

problems with acetaminophen

A

liver toxicity and death due to saturation of glucuronidation, sulfation, and GSH conjugation reactions, yielding toxic NAPQI

91
Q

treatment of acetaminophen posioning

A

N-acetylcysteine

92
Q

non selective reversible NSAIDS

A

inhibit cox-mediated generation of proinflammatory eicosaniods
anti-inflammatory, antipyretic, analgesic

93
Q

how to antipyretics work

A

most likely related to ability to decrease PGE2 levels in regions of the brain surrounding the hypothalamus

94
Q

how doe PGEs, PGI2, and LTB4 lower threshold of nociceptors

A

sensitizing afferent nerve endings to effects of chemical or emchanical stimuli

inhibition will raise threshold of nociception

95
Q

clinical indications for non-selective reversible NSAIDs

A 
mild to moderate pain
dysmenorrhea
fever
gout
osteoarthritis, rheumatoid arthritis
patent ductus arteriosus closure
96
Q

non-selective reversible NSAIDs

A

increase incidence of stomach or intestinal ulcers especially in elderly
bleeding
fluid retention, kidney failure
hypertension

97
Q

basics of non-selective reversible NSAIDs

A

pharmacodynamics not kinetics predict response
indication and efficacy vary
in one is not effective, substitute
each attempt with a dose to reach maximum anti-inflammatory range is about 2 weeks

98
Q

what are the acetic acid derivatives

A

indomethacin, diclofenac, ketorolac

inhibit COX, promotes incorporation of unesterified AA into triglycerides to reduce availability

99
Q

indomethacin

A

can directly inhibit neutrophil motility

no longer first choice NSAID due to GI toxicity

100
Q

diclofenac

A

can alter FA transport and reduce intracellular AA

more potent anti-inflammatory agent than indomethacin

101
Q

ketorolac

A

primarily used for its strong analgesic properties

only NSAID approved for parenteral use, uses short term due to more side effects

102
Q

what are the propionic acid derivatives

A

ibuprofen, naproxen

103
Q

ibuprofen

A

relatively potent analgesic used in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, primary dysmenorrhea

better than indomethacin

104
Q

naproxen

A

has long plasma half life
more potent than aspirin
directly inhibits leukocytes function and causes less severe GI adverse effects than aspirin

105
Q

indications for naproxen

A

for patients resistant to other propionic acid derivatives

it is presented in pur active isomer while others need to be activated

106
Q

oxicam derivatives and others

A

piroxicam

107
Q

piroxicam

A

efficacious as aspirin, naproxen and ibuprofen in treatment of rheumatoid arthiris and osteoarthritis but better tolerated

inhibits collagenase, proteoglycanase and oxidative burst to modulate neutrophil function

long half life-57 hrs, give daily

108
Q

problem with COX-2 inhibitors

A

COX-2 is essential for kidney function and major enzyme for PGI2 produciton which opposes TXA2 in platelets

109
Q

COX-2 selective inhibitors

A

celecoxib

110
Q

celecoxib

A

anti-inflammatory, antipyretic, and analgesic similar to other non-selective cox inhibitors

no anti-platetlet

111
Q

clinical indications for celecoxib

A 
acute pain
primary dysmenorrhea
nakylosing spondylitis
osteoarthritis 
rheumatoid arthritis
112
Q

adverse effects for celecoxib

A

increased incidence of MI, stroke, heart failure
peripheral edema
exacerbation of asthma
GI bleeding (less than non-selective NSAIDs)

113
Q

selective eicosanoid inhibitors

A

LOX inhibitors

LT receptor antagonists

114
Q

LOX inhibitors info

A

leukotriene mediated pathophysiology includes

asthma, inflammatory bowl disease, rheumatoid arthritis, current pharmacoloic agents only target asthma

115
Q

what is a LOX inhibitor

A

zileuton

116
Q

zileuton

A

selective 5-LOX inhibitor
chelates nonheme iron on 5-LOX to inhibit LTB4,C4,D4 and E4 formation

indicated for asthma, not use due to low bioavailability, low potency, and liver toxicity

117
Q

LT receptor antagonists

A

montelukast

zariflukast

118
Q

montelukast, zafirlukast

A

LTD4 receptor antagonist
LTC4 and LTE4 also bind to LTD4 recetor with less affinity
both are indicated for asthma
montelukast is also indicated for seasonal allergic rhinitis

119
Q

non-selective eicosanoid inhibitors

A

cytokine inhibitor

glucocorticoids

120
Q

what causes upregulation of COX-2 mRNA and increased PG synthesis

A

cytokines (IL TNFa) released from damaged cells or immune cells

121
Q

anti-TNFa or anit-IL agents bind where and do what

A

binds to cytokines and prevent them from activating the eicosanoid pathways involved in inflammation

aspirin-triggered lipoxins also block TNFa

122
Q

glucocorticoids

A

inhibit phospholipase A2 and prevent AA release

limit inflammation by limiting AA inflammatory mediators

123
Q

glucocorticoids are what kind of anti-inflammatory drugs

A

steroidal, in contrast with NSAIDS

124
Q

chronic uses of glucocorticoids

A

associated with osteoporosis, muscle wasting, and abnormal carbohydrate metabolism

125
Q

glucocorticoids actions

A

not limited to inhibition of PLA2

not direct inhibitors of PLA2

126
Q

4 things glucocorticoids do

A

induce lipocortins that inhibits PLA2

induce lipocortins on leukocytes to inhibits pro-inflammatory response by activiating lipoxin A4 receptor

repress COX-2 gene and ezyme expression

respress cytokine expression that activates COX-2

MSK exam 1 (3 decks)

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