Antipyretics, Antiimflamm, Anagesics

Question 1

what cleaves AA from membrane P-lipids?

Answer 1

P=lipase A2**(main ptwy) & C

Question 2

where/from what is AA made?

Answer 2

liver; linolEic acid (essential FA)

Question 3

What enzyme makes LTs from AA?

Answer 3

Lipoxygenase

Question 4

What enzyme makes PGs and TXs from AA?

Answer 4

PGH synthase (peroxidase + either COX-1 or COX-2)

Question 5

What PG is made from AA+COX?

Answer 5

PGH2; c15 hydroxyl grp important… ?

Question 6

Which enzyme makes PGI2 from PGH2?

Answer 6

prostacyclin synthase

Question 7

What is another name for PGI2?

Answer 7

prostacyclin

Question 8

Which enzyme makes TXA2 from PGH2?

Answer 8

thromboxane synthase

Question 9

Which enzyme makes PGE2 from PGH2?

Answer 9

endoperoxide isomerase

Question 10

Which enzyme makes PGF2α from PGH2?

Answer 10

endoperoxide reductase

Question 11

where is COX-1 found (constitutive or inducible or both)?
where is COX-2 found (constitutive or inducible or both)?

what increases or decreases if constitutive?

Answer 11

COX-1 constitutive form; blood vessels, stomach (increase mucous production - housekeeping function!)& kidney

COX-2 inducible form; immune/inflamm cells?;
- Involved in inflammation
- Levels elevated by inflammation & cytokines
- Decreased by administration of glucocorticoids
COX-2 constitutive form; brain and kidneys

Question 12

MOA of PGs (general)

Answer 12

interact w/ GPCR (auto/paracrine)
can -↑↓ of adenylate cyclase
-stimulation of phosphatidylinositol

Major effects on smooth muscle; other effects on platelets, kidney, CNS, endocrine organs, eye

Question 13

PROSTACYCLIN (PGI2)

• where synthesized?
• physio actions on 5 major sites of action
  
  • 1 minor

Answer 13

Synthesized by both vascular smooth muscle cells and endothelial cells (major contributor of COX2)

Major physio actions
1 circulation:
-powerful Vasodilator
-Inhibits platelet aggregation
2 airways: powerful broncho*dilator
3 GI: Inhibits gastric acid secretion; increase mucus secretion housekeeping
4 Reproductive: relaxes (unlike other prostaglandins(E2; TXA2; GF2a) that contract) uterine muscle
5 Pain: Induces pain by lowering the threshold of nociceptors

minor
6 Renal: Enhances renal excretion of sodium & water

Question 14

PROSTAGLANDIN (PGE2)

major physio actions

Answer 14

• weird low [ ] enhances platelet aggregation (high inhibits - just like with PGI2 - aka prostacyclin)
  -vasodilator and bronchodilator like prostacylin
  d) GI- Inhibits gastric acid secretion & stimulates gastric mucus secretion housekeeping
  [e.g. Misoprostol (Arthrotec, Cytotec) used to prevent ulcers produced by NSAID]
  f) Reproductive- Uterine smooth muscle, *increases contraction
  -Fever: PGE2 IS A DIRECT PYROGEN IN HYPOTHALAMUS
  PMN’s release cytokines (interleukin-1) which cross into hypothalamus; Interleukin-1 increases PGE2 levels

Question 15

THROMBOXANE (TXA2)
where synth’d
major physio actions

Answer 15

synthesized by platelets, lung, kidney and other sites
Vaso*constriction
Stimulates platelet aggregation (major product of platelet COX1)

Question 16

PGF2α

major physio actions

Answer 16

a) Vascular- Vaso*constrictor
b) Airway- *contracts airway smooth muscle cells
c) Reproductive - Contracts uterine smooth muscle/dysmenorrhea (pain)
* * d) eye- decreases intraocular pressure – used to treat glaucoma (condition associated w loss of COX2 in the eye)

Question 17

what enzyme is used on AA to make leukotrienes?

Answer 17

5-lipoxygenase

Question 18

what are the important precursors in LT synth?

Answer 18

5-HETE -> LTA4

Question 19

What LTs come from LTA4? (2)

Answer 19

LTB and LTC (both are 4)

Question 20

What LTs come from LTC4? (2)

Answer 20

LTD and LTE (both are 4)

Question 21

which 2 LTs are chemotactic agents?

Answer 21

5-HETE and LTB

Question 22

what is another name for LTC -> D,E?

Answer 22

all 3 collectively called “cysteinyl leukotrienes”

Question 23

what 3 things are the cysteinyl LTs (LTC,D,E) involved in?

Answer 23

• potent broncho constrictor
• increase vascular permeability (edema)
• components of slow reacting substance of anaphylaxis (SRS-A)