Eicosanoids

Question 1

Arachidonic acid

Answer 1

Precursor for COX, lipoxygenases and cytochrome P-450 monooxygenases

Question 2

Cyclooxygenases

Answer 2

Two forms and two activities

1. Oxygenates AA to PGG2
2. Peroxidase PGG2 to PGH2

Question 3

COX-1 vs COX-2

Answer 3

Both heme, membrane-bound
COX-2 larger active site
On different chromosomes
COX-1 is constitutive
COX-2 is inducible
Glucocorticoids decrease expression of COX-2

Question 4

Zileuton

Answer 4

Lipoxygenase
Oral administration
Metabolized by CYP enzymes
Mechanism- inhibits cys-LT(bronchoconstriction)
Adverse effects- can increase liver enzymes
Therapeutic use- treat mild asthma

Question 5

Zarfirlukast

Answer 5

Cysteinyl Leukotriene receptor antagonist
Oral administration
Metabolized by CYP2C9/3A4
Mechanism- inhibits Cys-LT
Therapeutic use- treat mild asthma

Question 6

PGF2α

Answer 6

Bronchoconstrictor, myometrial contraction, vasoconstriction

Question 7

PGI2

Answer 7

Vasodilator, hyperalgesic, stops platelet aggregation

Question 8

TXA2

Answer 8

Vasoconstrictor, thrombotic (promotes platelet aggregation)

Question 9

PGE2

Answer 9

hyperalgesic

Question 10

Pain

Answer 10

PGE2, PGI2 sensitize nerve endings

COX-2 is in dorsal root of spinal cord which makes PGE2 in spinal cord

Question 11

Fever

Answer 11

Increase cytokines
PGE2 from vascular endothelial cells via COX-2
Activate area of hypothalamus increasing temp

Question 12

Platelets

Answer 12

PLA2 cause AA -> TXA2 via COX-1 cause aggregation

Endothelial cells make PGI2 to inhibit aggregation

Question 13

Uterus effects

Answer 13

In pregnancy
PGI2- quiescent state
PGE2- initiate labor and cervical ripening EP4 receptor
PGF2α- contracts uterus in labor
Non-pregnant
PGF2α-dysmenorrhea

Question 14

PGD2

Answer 14

Vasodilator in periphery, vasoconstrictor in pulmonary

Question 15

Ductus Arteriosus

Answer 15

PGE2 effects the tone
Relaxation via EP4 receptor
COX-2 plays a role
Developmentally regulated- loss of response in neonate, loss of placenta, increase pulmonary BF, decrease in EP receptor

Question 16

Bronchial/Tracheal smooth muscle

Answer 16

PGF2α and PGD2 contract
PGE2 relaxes
TXA2 constricts bronchial sm
PGI2 relaxes bronchial sm

Question 17

Kidney

Answer 17

PGE2, PGI2 increase renal blood flow

Question 18

GI secretions

Answer 18

COX-1 promotes protective PG
PGE2 and PGI2 inhibit gastric secretion and gastric mucosal blood flow
PGE2 stimulates mucus release, bicarbonate secretion and smooth muscle

Question 19

Dinoprostone

Answer 19

Analog of PGE2
Used for cervical ripening via gel via EP4 receptor
Used for termination of early pregnancy via vaginal suppository via uterine contractions and EP1/3 receptors
Adverse effects- GI-related, fever, uterine rupture

Question 20

Carboprost Tromethamine

Answer 20

PGF2α analog
IM injection
Used for termination of second trimester pregnancy
Used for controlling postpartum hemorrhage
Adverse effects- GI-related, fever, uterine rupture

Question 21

Misoprostol

Answer 21

PGE1 analog
Used as replacement therapy to prevent ulcers when individuals are on long term NSAID
Stimulates EP3 receptor
Increase mucin and bicarbonate and mucosal BF
Adverse effect- diarrhea
CONTRAINDICATED IN PREGNANCY

Question 22

Alprostadil

Answer 22

PGE1 analog
Used for erectile dysfunction via intracavernous injection
Used for maintenance of ductus arteriousus via IV
Increase cAMP to relax smooth muscle
Adverse effects- pain at injection site, prolonged erection and apnea in 10% of neonates

Question 23

Epoprostenol

Answer 23

PGI2 analog
Used in pulmonary hypertension via IV
Adverse effects- nausea, vomiting, headache, flushing

Question 24

Bimatoprost

Answer 24

PGF2α analog
Treat glaucoma by increasing outflow of aqueous humor
Can increase eyelashes
Adverse effects- redness of eyes, itching, change in eye color, unwanted hair growth