Eicosanoids Flashcards
1
Q
Eicosanoids
A
Prostaglandins, Thromboxane, Leukotrienes
- 20 carbon structure
- Arachidonic acid ⇒ most common precursor in humans
2
Q
Leukotrienes
A
- Made by inflammatory cells upon ⊕ of PLA2 and Lipoxygenase (5-LOX)
-
Leukotriene C4 and D4 (LTC4 and LTD4)
-
Slow-reacting substance of anaphylaxis (SRS-A)
- Airway inflammation and edema
- Bronchoconstriction
- Secretion of thick mucus
- More potent than histamine but slower onset and longer duration
-
Slow-reacting substance of anaphylaxis (SRS-A)
3
Q
Zarfirlukast and Montelukast
A
Leukotriene Antagonists
- Alternatives for long-term control of mild to moderate asthma and seasonal allergies
- ↓ Incidence of attacks
- Not used for acute treatment
- Max effects can take weeks
-
Zarfirlukast ⇒ ⊗ CYP2C9 and CYP3A4
- Drug interactions
- Montelukast ⇒ does not interact with CYP450 system
4
Q
Zilueton (Zyflo)
A
5-Lipoxygenase Inhibitor
- Alternative for long-term control of mild to moderate asthma
- Must be taken 4x/day ⇒ compliance issues
- ⊗ CYP1A2 and CYP3A4 ⇒ drug interactions
-
Adverse effects:
- Flu-like symptoms
- GI upset
- Elevation of liver enzymes
5
Q
Prostaglandins
Overview
A
- Production stimulated by ⊕ of PLA2
- Trauma or specific stimuli
- Act as autocrine and paracrine mediators
- Short half-life and act rapidly near site of synthesis ⇒ autacoids
- Share a common prostanoid structure
- Produced by most cells
- Relative abundance of each product depends on enzyme pattern
6
Q
Prostaglandins
Platelet Effects
A
-
Vessel injury ⇒ platelet binds to endothelium ⇒ activation ⇒ Thromboxane A2 (TXA2) synthesis by platelets
- COX1 is the major enzyme responsible
- TXA2 ⇒ platelet aggregation & vasoconstriction
-
Endothelium releases Prostacyclin I2 (PGI2)
- COX2 is the major enzyme responsible
- PGI2 ⇒ ⊗ platelet aggregation & vasodilation
-
ω-3 fatty acids found in fish oils ⇒ synthesis of thromboxane A3 (TXA3)
- Weaker form ⇒ ↓ in strokes and heart attacks
7
Q
Prostaglandins
Renal Effects
A
- Kidney makes PGE2 and PGI2
-
Vasodilation of afferent arteriole
- Esp. in pts w/ renal insufficiency and the elderly
- Maintains renal blood flow and glomerular filtration
- ↑ sodium and water excretion
-
Vasodilation of afferent arteriole
-
COX inhibitors ⇒ ⊗ prostaglandin synthesis
- Disrupt RBF balance
- Can cause HTN or kidney failure
8
Q
Prostaglandins
Cardiac Effects
A
-
PGE2 and PGI2 maintain patency of ductus arteriosus (PDA)
- Usually closes shortly after birth
- In some cases, esp. premature births, it remains open
- Indomethacin or ibuprofen ⇒ COX inhibitors used to close a PDA
-
Need to maintain PDA patency in some cases of congenital heart problems pending surgery
- Done using Alprostadil ⇒ PGE1 analogue
9
Q
Prostaglandins
Pulmonary Effects
A
PGE2 and PGI2 ⇒ arterial vasodilation in the lung ⇒ ↑ pulmonary blood flow
10
Q
Epoprostenol
(Flolan)
A
PGI2 analogue
- Used to treat primary and secondary pulmonary HTN
-
Adverse effects:
- Hypotension
- Flushing
- Headache
- Nausea and diarrhea
-
Other possible treatments are:
- Calcium channel blocker (nifedipine)
- Supplemental oxygen
- Bosentan (endothelin antagonist)
- Sildenafil (phosphodiesterase inhibitor)
11
Q
Alprostadil
A
PGE1 analogue
- Causes penile vasodilation
- Given by injection to treat erectile dysfunction
12
Q
Trimix
A
Alprostadil (PGE1 analogue) + Papaverine (? phosphodiesterase inhibitor) + Phentolamine (α-blocker)
Given via injection for erectile dysfunction.
13
Q
Prostaglandins
Female Reproductive Effects
A
14
Q
Prostaglandins
Glaucoma Therapy
A
15
Q
Dinoprostone
A
PGE2 analgoue
Given as a vaginal gel or insert
-
Induces labor by:
- ↑ proteoglycan content & ∆ biophysical properties of collagen ⇒ cervix softening
- ⊕ Uterine contraction
- May be used as an abortifacient
- May cause nausea, vomiting, or diarrhea
18
Q
Latanoprost
A
- Long-lasting PGF2 derivative
- ↑ Outflow of aqueous humor through uveoscleral pathway ⇒ ↓ IOP
- Used to treat glaucoma
-
Side effects:
- ↑ Eyelash length
- May change iris color
