Phar 341 - Prostaglandins And Leukotrienes

Front 1

Arachidonic acid is released or mobilized from cell membranes phospholipids by: (3)

Back 1

1. Phospholipase A2

2. Phospholipase C

3. Diglyceride lipase

Front 2

What are isoprostanes?

What are their functions?

Back 2

Prostaglandin stereoisomers.

They can bind to prostaglandin receptors as a potent vasoconstrict and may contribute to inflammation.

Front 3

How are isoprostanes synthesized?

Back 3

Formed by perioxidation of arachidonate by free radicals while part of cell membrane.

COX (cyclooxygenases) not needed.

Front 4

How does COX -1 and COX-2 differ, in terms of how they are expressed.

Back 4

COX 1 - expressed all the time, in all cells

COX 2 - expression is inducible

Front 5

Which enzymes synthesize prostaglandins?

Back 5

COX (cyclooxygenase)

Front 6

What group of drugs blocks COX? (giggle giggle)

Back 6

Non-steroidal anti-inflammatory drugs (NSAIDs)

Front 7

The precursor for prostaglandins and thromboxanes:

Back 7

PGH2

Front 8

T/F: Most cells make several types of prostanoids.

Back 8

False.

Most cells make one or two dominant ones.

Front 9

T/F: Specific isomerases and synthases required for each type of prostaglandin.

Back 9

True.

Front 10

Label A, B, and C.

Back 10

A - Phospholipase A2, Phospholipase C and Diglyceride

B - Lipoxygenase

C - Cyclooxygenase

Front 11

Which receptors do PGE2 act on? (4)

Back 11

EP1

EP2

EP3

EP4

Front 12

Effects of EP1? (4)

Back 12

1. Mediate stress response

2. Inflammatory thermal hyperalgesia (e.g. sunburn)

3. Activate GI smooth muscle

4. Protect against NSAID ulcers (stomach)

Front 13

Effect of EP2? (3)

Back 13

1. Facilitate pain transmission (spinal cord)

2. Join inflammation

3. Fertility and uterine contraction

Front 14

Effects of EP3? (6)

Back 14

1. Fever generation

2. Angiogenesis (inflammation and cancer)

3. Activate GI smooth muscles

4. Inhibit gastric secretions

5. Protect against NSAID induced ulcers (intestines)

6. Mediates pain associated from viruses

Front 15

Effects of EP4? (6)

Back 15

1. Increase bone turnover
2. Vasodilatation
3. Sensitize nociceptors & neurons
4. Pro-inflammatory in joint
5. Anti-inflammatory in duodenum
6. Promotes mucus secretion in stomach

Front 16

Which receptors do PGD2 act on?

Back 16

DP (1, 2)

Front 17

Effect of DP (1,2)? (3)

Back 17

1. Bronchoconstriction

2. Inhibits platelet aggregation

3. Promotes sleep

Front 18

Which receptor does PGI2 act on?

Back 18

IP

Front 19

Effects of IP? (7)

Back 19

1. Vasodilation

2. Bronchodilation

3. Inhibit platelet aggregation

4. Angiogenesis (cancer)

5. Increase renal H2O and Na clearance

6. Uterine relaxation

7. Sensitize nocireceptors

Front 20

Which receptors does PGF2a act on?

Back 20

FP (A, B)

Front 21

Effects of FP (A,B)? (5)

Back 21

1. Vasoconstriction

2. Activate GI smooth muscles

3. Bronchoconstrictor

4. Uterine contraction

5. Regulate IOP

Front 22

Which receptor does TXA2 act on?

Back 22

TP (A,B)

Front 23

What did sushi A say to sushi B?

Back 23

WASABI!!

Front 24

Effects of TP(A,B)? (7)

Back 24

1. Potent vasoconstrictor

2. Potent bronchoconstrictor

3. Mitogen (smooth muscle)

4. Promotes platelet aggregation

5. Angiogenesis (cancer)

6. Decrease renal function

7. Uterine contraction

Front 25

Which prostaglandins (and receptors) protect against NSAID ulcers? (2)

Back 25

1. PGE2 - EP1 - Stomach

2. PGE2 - EP3 - Intestines

Front 26

Which prostaglandins (and receptors) regulate vasodilation and constriction? (4)

Back 26

1. PGE2 - EP4 - Vasodilation

2. PGF2a - FP (A,B) - Vasoconstrict

3. PGI2 - IP - Vasodilate

4. TXA2 - TP(A,B) - Potent vasoconstrictor

Front 27

Which prostaglandins (and receptors) cause bronchoconstriction? (3)

Back 27

1. PGD2 - DP(1,2)

2. PGF2a - FP(A,B)

3. TXA2 - TP(A,B)

Front 28

What is the function of corticosteroids? (2)

Back 28

1. Blocks synthesis pathways for PG and LT
2. Blocks phospholipase A2

Front 29

How do NSAIDs act as analgesics?

Back 29

Blocks synthesis of PGE2 in periphery and CNS.

Front 30

How do NSAIDs treat dysmenorrhea?

Back 30

Blocks synthesis of PGE2 and PGF2, which cause contractions.

Front 31

How do NSAIDs treat patent ductus arteroisis?

Back 31

Blocks PGE2 synthesis. PGE2 keeps fetal ductus arteriosus open.

Front 32

How are prostaglandins metabolized?

Back 32

They are oxidized by prostaglandin 15-OH dehydrogenase, and also undergo hydrate to inactive metabolites. Inactive metabolites are excreted in urine.

Front 33

1. MOA and 2. therapeutic use of Alprostadil?

Back 33

1. Is a prostaglandin agonist - PGE2 analogue (also know as PGE1)

2. Is a vasodilator, for treatment of ED (intracavernosal injection; secondary option) and ductus arteosus patent in neonates awaiting cardiac surgery.

Front 34

Adverse effects of Alprostadil?

Back 34

Penile pain, common in IC injections (NO REALLY.)

Front 35

What is Bruce Lee's favourite drink?

Back 35

wa-TAAAAAA!

Front 36

1. MOA and 2. therapeutic use of Dinoprostone?

Back 36

1. EP receptor agonist (PGE1 derivative). Promotes uterine contraction and cervical ripening.

2. Used at end of term for child birth or abortion (1/2 trimester)

Front 37

Adverse effects of Dinoprostone?

Back 37

Abdominal discomfort and diarrhea.

Front 38

1. MOA and 2. Therapeutic use of misoprostol?

Back 38

1. EP receptor agonist (PGE1 derivative). Is cytoprotective at low doses (GI), and inhibits gastric secretion at high dose.

2. Prevents NSAID-induced ulcers and causes early abortions.

Front 39

Adverse effects of misoprostol?

Back 39

Abdominal pain, diarrhea

Front 40

Which prostaglandins (and receptors) regulate platelet aggregation? (3)

Back 40

1. PGD2 - DP (1,2) - Inhibits

2. PGI2 - IP - Inhibits

3. TXA2 - TP (A,B) - Promotes

Front 41

What effect would a selective agonist at the EP2 receptor have if administered in a joint?

Back 41

Inflammation

Front 42

1. MOA and 2. Therapeutic use of Lubiprostone?

Back 42

1. Is a metabolite of PGE1. It is metabolized in the GI with very little absorption. It activates voltage-dependent chloride channels on the apical membrane of intestinal epithelial cells. This causes secretion of fluid into the intestines.

2. Treatment of chronic constipation.

Front 43

Adverse effects of Lubiprostone?

Back 43

Vomiting, nausea, abdominal cramping

Front 44

1. MOA and 2. Therapeutic use of Latanoprost?

Back 44

1. A PGF2 derivative.

2. Used topically for lower IOP in glaucoma.

Front 45

1. MOA and 2. Therapeutic use of Prostacyclin (Epoprostenol)?

Back 45

1. Is a PGI2 analogue, made mainly in vascular endothelium. Is a powerful vasodilator and inhibits platelet aggregation. Used for vascular homeostasis.

2. Used for pulmonary hypertension and porto-pulmonary hypertension (secondary to liver disease).

Front 46

Therapeutic use of TXA2-receptor antagonists and synthesis inhibitors?

Back 46

Originally developed for cardiovascular indications, but no clinical use is established.

Front 47

1. MOA and 2. Therapeutic use for Acetylsalicylic acid (ASA)?

Back 47

1. Blocks off synthesis of TXA4 for the life of the platelet, therefore decreasing platelet aggregation.

2. Is an anticoagulant and used for secondary prevention of myocardial infarction.

Front 48

Adverse events of ASA?

Back 48

GI ulceration

Inhibition of PGE2

Front 49

Which enzyme converts arachidonic acid to leukotrienes?

Back 49

Lipoxygenases (LOX)

Front 50

Which cells are 5-lipoxygenase found in?

Back 50

Inflammatory cells:

- polymorphonuclear leukocytes (PMN)

- basophils

- mast cells

- eosinophiles

- macrophages

Front 51

What are the primary products of 5-LOX?

Back 51

LTB4. This can be converted into lipoxins LX4A, LXB4, and other leukotrienes.

Front 52

Which receptor does LTB4 act on?

Back 52

BT1,2

Front 53

What are the effects of receptor BT1,2? (2)

Back 53

1. Chemoattractant

2. Activates inflammatory cells

Front 54

What do you get when you cross a stream and a brook?

Back 54

Wet feet!

Front 55

Which receptor do LTC4, D4, E4 act on?

Back 55

CystLT1,2

Front 56

Effect of receptor CystLT1,2 (aka cysteinyl-leukotrienes)? (2)

Back 56

1. Chemoattractant (eosinophil)

2. Potent bronchoconstrictor (induces bronchial inflammation)

Front 57

1. MOA and 2. Therapeutic use of Zileuton?

Back 57

1. Zileuton is a 5-lipoxygenase inhibitor.

2. Used for asthma.

Front 58

Adverse effects of Zileuton?

Back 58

Elevated liver enzymes, indigestion, abdominal pain, nausea.

Metabolized by cytochrome P450, may alter metabolism of drugs such as warfarin, theophylline, and propanolol.

Front 59

1. MOA and 2. Therapeutic use of Montelukast?

Back 59

1. Competitive antagonist at CystLT1 receptor.

2. Used for asthma, allergic rhinitis.

*Unknown if this receptor is relevant for treating asthma.