Block 2_4 - Eicosanoids

Question 1

Zileuton

Pharmacokinetics (route of admin, metabolism)

Mechanism

Adverse Effects

Therapeutic Use

Answer 1

Inhibitor of 5 Lipoxygenase (leukotriene synthesis)

1.

• oral administration; half life of 2.5 hrs
• metabolized by CYP enzymes (CYP1A2, 3A4, 2C9)

2.

• Inhibits 5-lipoxygenase
• no production of any Leukotrienes
• inhibits cys-LTs (LTC4, LTD4) AND LTB4

3. few, increase liver enzymes
4. prophylactic and chronic treatment of mild asthma (not for acute asthma attacks)

Question 2

Zafirlukast

Pharmacokinetics (route of admin, metabolism)

Mechanism

Adverse Effects

Therapeutic Use

Answer 2

1. oral administration; half life of10 hrs
   - metabolized by CYP2C9/3A4
2. cysteinyl leukotriene (cys-LTs) receptor antagonist
   - does not inhibit biosynthesis
3. minimal
4. prophylaxis and chonic treatment of mild asthma (not for acute asthma attacks)

Question 3

Dinoprostone

1. Therapeutic Use #1
2. Preparation
3. Mechanism of Action
4. Adverse Effects (for both)

5. Therapeutic Use #2
6. Preparation
7. Mechanism of Action

Answer 3

(PGE2 analog)

1. Cervical ripening in pregnancy
2. cervical gel - 0.5 mg (1.5 mg max)
3. promotes cervical ripening (activation of collagenase - breakdown of collagen)
   - relaxes cervical smooth muscle
   - EP4 Receptor. increase cAMP
4. (for both) GI-related (nausea, vomiting, diarrhea), Fever, Uterine Rupture (in women with history of C-section or other uterine surgery)

5. termination of early pregnancy/abortion
6. vaginal suppository - dissolves after insertion (20 mg: maximal dose 240 mg)
7. uterine contractions via EP1/EP3 receptors, increase Calcium

Question 4

Misoprostol

1. Therapeutic Use
2. Preparation
3. Mechanism of Action
4. Adverse Effects

Answer 4

PGE1 Analog

1. “replacement therapy” for prevention of ulcers caused by long-term administration with NSAIDs
2. oral administration/requires 4x/day dosing
3. • suppresses gastric acid secretion by stimulating EP3 receptors on parietal cells
     - decrease in cAMP
     - increase in mucin and bicarbonate secretion
   • increase mucosal blood flow
4. diarrhea; contraindicated (i.e. should be avoided) in pregnancy

Question 5

Alprostadil

1. Therapeutic Use
2. Preparation
3. Mechanism of Action
4. Adverse Effects

5. Therapeutic Use
6. Preparation
7. Mechanism of Action
8. Adverse Effects

Answer 5

PGE1 analog

1. impotence/erectile dysfunction
2. intracavernous injection
3. increase in cAMP which relaxes smooth muscle of corpus cavernosum; acts through EP2/4 receptors
   * - relaxation of trabecular smooth muscle and dilation of cavernosal arteries/leads to entrapment of blood*
4. priapism - prolonged rection more than 6 hrs

5. temporary maintenance of patent ductus arteriosus until surgical correction
6. IV infusion
7. EP2/4 receptors; cAMP-mediated relaxation of ductus arteriosus smooth muscle
8. Apnea in about 10% of noenates;

Question 6

Epoprostenol

1. Therapeutic Use
2. Preparation
3. Mechanism of Action
4. Adverse Effects

Answer 6

PGI2

1. primary pulmonary hypertension
   
   • rare, idiopathic disease observed in young adults, increased incidence in females
   • leads to right heart failure/frequently fatal
2. continuous IV infusion
3. IP receptor; cAMP-mediated dilation of pulmonary artery vascular smooth muscle
4. nausea, vomiting, headache, flushing
   
   • potential drug interactions (other anti-hypertensive therapy, antiplatelet therapy)

Question 7

Bimatoprost

1. Therapeutic Use
2. Preparation
3. Mechanism of Action
4. Adverse Effects (for both)

5. Therapeutic Use
6. Preparation
7. Mechanism of Action

Answer 7

PGF2α

1. glaucoma
2. ophthalmic solution
3. increases outflow of aqueous humor
4. Eye redness, itching, changes in eye color (increased brown pigment), (excessive) increase length and number of eyelashes

5. eyelash hypotrichosis (inadequate eyelashes)
6. ophthalmic solution
7. increase the precent and duration of hairs in the growth phase

8.