Prostaglandins and Leukotrienes Flashcards
1
Q
Synthesis of Prostagladins, Leukotrienes, and Isoprostanes starts with:
A
- Arachidonic acid (AA) is released from the cell membrane by phospholipase A2, phospholipase C, and diglyceride lipase
2
Q
Examples of Prostaglandins
A
- COX 1 (cyclooxygenase)
- COX 2
- LOX (Lipoxygenase)
3
Q
Expression of COX 1
A
- expressed constitutively in most cells
4
Q
Expression of COX 2
A
- indubile
- expression depends on certain stimuli
5
Q
Synthesis of Prostagladins
A
- PGH2 is the precursor of prostaglandins and thromboxanes
- specifc isomerases and synthases for each unique PG
6
Q
Synthesis of Leukotrienes
A
- LOX converts AA to leukotrienes
7
Q
Prostaglandin PGE2 can bind to which receptors:
A
EP1
EP2
EP3
EP4
8
Q
Prostaglandin PGD2 can bind to which receptors:
A
DP (1,2)
9
Q
Prostaglandin PGF2 alpha can bind to which receptors:
A
FP (A,B)
10
Q
Prostaglandin PGI2 (prostacyclin) can bind to which receptors:
A
IP
11
Q
Thromboxane TXA2 can bind to which receptors:
A
TP (alpha, beta)
12
Q
Effects of EP1
A
- activates GI smooth muscle
- protects against NSAID ulceration in stomach
13
Q
Effects of EP2
A
- facilitates pain transmission (spinal cord)
14
Q
Effects of EP3
A
- mediates fever generation
- inhibits gastric acid secretion
- protects against NSAID ulceration in intestines
15
Q
Effects of EP4
A
- sensitize npciceptors and neurons
- pro-inflammatory in joint
- promotes mucus secretion
16
Q
Effects of DP(1,2)
A
- bronchoconstriction
- promote sleep induction
17
Q
Effects of FP(A,B)
A
- vasoconstriction
- bronchoconstriction
- regulation of intraocular pressure
18
Q
Effects of IP
A
- vasodilation
- inhibition of platelet aggregation
- uterine relaxation
- sensitize nociceptors
19
Q
Effects of TPAB
A
- potent vasoconstriction
- potent brochoconstriction
- promote platelet aggregation
20
Q
Leukotriene LTB4 binds to which receptor:
A
BT1,2
21
Q
Leukotrienes LTC4,D4,E4 bind to which receptor:
A
CystLT1,2
22
Q
Effects of BT1,2
A
- chemoattractant (PMNs)
- activates inflammatory cells
23
Q
Effects of CystLT1,2
A
- chemoattractant (eosinophils)
- potent brochoconstriction (induces bronchial inflammation)
24
Q
Prostaglandin Synthesis Inhibitors
A
- corticosteroids
- NSAIDs
25
How Corticosteroids inhibit prostaglandin synthesis
- block all the known pathways of PG and LT synthesis
| - block phospholipase A2
26
How NSAIDs inhibit prostaglandin synthesis
- block COX (prostaglandin and thromboxane)
| - may promote synthesis by LOX of leukotrienes
27
How NSAIDs work as analgesics
- blocks formation of all prostaglandins (PGE2) peripherally (and in the CNS)
28
How NSAIDs work form dysmenorrhea
- increase endometrial synthesis of PGE2 and PGF2 causes the pain
- block PGE2 synthesis which causes pain
29
How NSAIDs work for Patent Ductus Arterious
- PGE2 keeps the fetal ducts arteriosus open (normally closes at birth)
- block PGE2 synthesis to get the duct to close
30
Porstaglandin Agonists
- Alprostadil
- Dinoprostone
- Misoprostol
31
How Alprostadil works
- PGE1-analogue of PGE2
| - vasodilator
32
Therapeutic use of Alprostadil
- maintain the ductus arterosus patent in neonates awaiting cardiac surgery
- 2nd line treatment for erectile dysfunction
33
How Dioprostone works
- PGE1-derivative
| - promotes uterine contractions and cervical ripening
34
Therapeutic uses for Diprostone
- at end of term -> to facilitate delivery
| - 1st/2nd trimester -> abortion
35
Adverse effects of Diprostone and Misoprostol
- abdomenal discomfort
| - diarrhea
36
How Misoprostol works
- PGE1-derivative
- cytoprotective at low doses
- inhibits gastric acid secretion at hig doses
37
Therapeutic uses of Misoprostol
- prevent NSAID induced peptic ulcers
| - used with antiprogestins for early abortion
38
Prostaglandin E Analogues
- Lubiprostone
39
How Lubiprostone works
- metabolite of prostaglandin E1 with low systemic absorption
- activates voltage-dependnet chloride channels on the apical membrane of intestinal epithelial cells
- increases chloride in intestinal tract which promotes intestinal fluid secretion leading to more rapid transit
40
Therapeutic use of Lubiprostone
- treatment of chronic constipation
41
Adverse effects of Lubiprostone
- vomitting, nausea, abdominal cramping
42
Prostaglandin F Agonist
- Latanprost (PGF2)
43
How Latanprost works
- topically active PGF2 derivative that lowers intraocular pressure
44
Therapeutic use of Latanoprost
- glaucoma
45
Prostaglandin I Agonist
- Prostacyclin (epoprostenol:PGI2)
46
How Prostacyclin works
- powerful vasodilator and inhibitor of platelet aggregation synthesized mainly by the vascular endothelium
- promotes blood flow
47
Therapeutic use for Prostacyclin
- pulmonary hypertension
| - porto-pulmonary hypertension
48
Thromboxane receptor antagonists and synthesis inhibitors
- prevent platelet aggregation and vasocontriction
49
5-lipoxygenase enzyme inhibitors
- Zileuton
50
How Zileuton works
- blocks LT4 synthesis
51
Therapeutic Use for Zileuton
- Asthma
52
Adverse Effects of Zileuton
- elevated liver enzymes, indigestion, abdominal pain, and nausea
- metabolized by CYP so it can alter metabolism of other drugs
53
Leukotriene-receptor inhibitors
- montelukast
54
How Montelukast works
- competitive antagonist at the CystLT1 receptor
55
Therapeutic uses for Montelukast
- asthma
| - allergic rhinitis
