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Pharmacology Test #3 > 11.26 arachidonic acid cascade > Flashcards

11.26 arachidonic acid cascade Flashcards

0
Q

Substrates are formed from:

A

polyunstaurated fatty acids (PUFA

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1
Q

NSAIDs act

A

locally and on demand, they do not have distant sites of action

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2
Q

PUFA can be metabolized by:

A

cyclooxygenase
lipoxygenase enzymes or
P450 “epoxygenase” (we aren’t really going to talk about epoxygenases)

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3
Q

phospholipases release PUFA precursors from

A

phospholipsds, and arachiadonic acid comes from PUFA

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4
Q

arachidonic acid structure

A

20 carbon molecules with 4 double bonds

kind of looks like a hair pin

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5
Q

first arachiodonic pathway

A

cycloxygenase pathway, produces the prostaglandins

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6
Q

types of cycloxygenase

A

COX 1 and COX-2

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7
Q

COX-1 is

A

constitutive (always on/always making PGs)

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8
Q

COX-2 is constitutive or inducible?

A

inducible (so when you injure yourself it will be present)

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9
Q

selective COX-2 inhibitors

A

Celecoxib (celebrex) blocks COX-2 therefore less GI and platelet effects

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10
Q

what is the only irreversible NSAID?

A

aspirin

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11
Q

selective COX-2 inhibitors

A

Celecoxib (celebrex) blocks COX-2 therefore less GI and platelet effects
-blocks production of COX-2 at the site of injury

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12
Q

good things that PGE2, PGF2a, and PGD2 do

A

decrease gastric acid, increase gastric mucous (protection), Ca2+ mobilization, sodium and water excretion
-so when you take NSAIDS you don’t get these benefits, and can get ulcers, water retention and swelling

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13
Q

cycloxygenase makes…

A

prostaglandins (PGE2, PGF2a, PGD2, PGI2, and Thromboxance A2

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14
Q

PGI2 (the two means it has two double bonds) does…

A
  • t 1/2=5 minutes
  • inhibits platelet aggregation
  • vasodilation
  • less sensitive to low doses of aspirin than thromboxane
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15
Q

bad things that PGE2, PGF2a, and PGD2 do

A 
-vasodilation
vasc permeability
sensitize to pain
increases body temperature
uterine contraction (cramps)
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16
Q

what is the major Lipoxygenase in our body?

A

5-lipoxygenase

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17
Q

lipoxygenase pathway leads to production of

A

-leukotrienes (C, D, and E)

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18
Q

Thromboxane A2

A
  • from the cyclo-oxygenase pathway
  • t 1/2=30 seconds
  • induces platelet aggregation
  • smooth muscle contraction
  • thus in smaller doses of aspirin it mostly affects thrombaoxane and not PGI2
  • inhibited by NSAIDs and aspirin
19
Q

Leukotriene actions (C, D, and E)

A

bronchial smooth muscle contraction, thus they are major players in asthma

21
Q

Zileuton

A

5-lipoxygenase inhibitor, will block both of the lipoxygenase pathways, it blocks the enzyme, whereas Zafirlukast and Montelukast block the receptors

21
Q

what class of drugs will inhibit all the pathways of AA?

A

antiinflammatory steroids, in inhibits phospholipase, thus these drugs have a lot of side effects

22
Q

if you wanted to inhibit just the production of the leukotrienes C, D, and E, what drug would you use?

A

Zafirlukast, Montelukast, the leukotrienes are still made, but these drugs block the receptors so they can’t bind

23
Q

leukotriene B4

A 
the second pathway in the lipoxygenase pathway
It increases the following:
-chemmotaxis
-WBC stickiness
-vascular permeability
-neutrophil secretion
24
Q

part of the oxygen radicals in the body come from where?

A

the cycloxygenase pathway

25
Q

COX-2 is present where?

A

in the brain and kidneys and in injured tissue

26
Q

all the prostaglandins act on what type of receptors?

A

G protein linked receptors

27
Q

txt of asthma

A

leukotriene blockers (5 LO inhibitor (Zileuton))

28
Q

what drug is not approved for patients less than 18 yr old?

A

Celecoxib (celebrex)

30
Q

Adverse effects and drug interactions of Celecoxib (celebrex)

A

abdominal pain, diarrhea,

31
Q

competitive leukotriene receptor blockers

A

Zafirlukast and montelukast

32
Q

how do NSAIDs promote the return to normal temperature from a fever?

A

they increase cytokines which increase the synthesis of PGE2 in the circumventricular organs

33
Q

effect of PGI2 and PGE2 in vascular smooth muscle

A

relax muscle =vasodilation but in the uterus, PGE2 has the opposite effect of smooth muscle constriction

34
Q

effect of Thromboxane A2 (TxA2) and LTC4 on vascular smooth muscle

A

contracts smooth muscle, vasoconstriction

35
Q

Arachidonic acid compounds are synthesized where?

A

they are synthesized LOCALLY, on DEMAND, and are not stored for future release. They also act locally. They are bound to the phospholipids of cell membranes and are released due to trauma and Phopholipase

36
Q

what is one of the key components (substrates) of the cycloxygenase pathway

A

oxygen, it will not work otherwise

37
Q

The leukotrienes C4, D4 and E4 play a major role in:

A

allergies and asthma

38
Q

prostaglandins (esp PGE2) effect in the hypothalamus

A

increase cAMP causing a rise in body temp (fever)

39
Q

what effect do LTC4 and LTD4 (leukotrienes) have in bronchial smooth muscle?

A

very potent contractors of airway smooth muscle (important in the increase in airway resistance in asthma and allergic rxns)

40
Q

effect of PGs in the GI

A

increase contraction and motility which can cause diarrhea, but they also increase mucous secretion and decrease gastric acid secretion in the stomach

41
Q

PGs in the uterus

A

contraction of uterine smooth muscle

-induction of abortion

42
Q

Which products of the cyclo-oxygenase pathway inhibit platelet aggregation?

A

PGI2

43
Q

role of prostaglandins in kidney function

A

they (PGI2 and PGE2) play a role in diuresis and increase Na+ and K+ excretion
-thus NSAIDs can cause fluid retention and in some part congestive heart failure

44
Q

drug that is used for anti-ulcer therapy, usually given to patients that are on NSAIDs therapy for extended amount of times

A

Misoprostol

45
Q

____ is used intra-amniotically to induce abortion, usually in pregnancy of longer than 15 weeks
-stimulates uterine contraction, break down collagen in cervix, synergize with oxytoc

A

Dinoprost (PGF2a) tromethamine

46
Q

____ is used in suppository form to induce abortion in pregnancies of less than 28 weeks. It is also used to induce full-term labor.
-stimulates uterine contraction, break down collagen in cervix, synergize with oxytocin

A

Dinoprostone (PGE2)

47
Q

formerly known as “the french abortion pill” ____ is usually taken within 9 weeks. It is not a prostaglandin, but must be taken with Misoprostol for the complete abortion to take place. what is the name of the drug, and how does it work?

A

(don’t really need to know) Mifepristone (RU-486), it blocks progesterone receptors causing the uterus to reject the implanted egg. It needs to be taken with misoprostol which causes the cervix to soften and dilate and the uterus to contract and expel the embry

Pharmacology Test #3 (9 decks)

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