Prostaglandins are derived from ____ which is a component of all cell membranes. It is released when phospholipase enzymes are released. Physical and chemical stimuli activate phospholipases such as ____. Phospholipase enzymes are inhibited by ____.
arachadonic acid, histamine, corticosteroids (this is why decadron halts n/v because it stops the release of prostaglandins)
Cyclooyxgenase is a complex of microsomal enzymes necessary for the synthesis of ___. What is their distribution?
Synthesis of prostaglandins, wide tissue distribution (all throughout the body)
COX has ___ tissue distribution. COX1 is found where? COX2 is found where?
Wide tissue distribution
COX1: platelets and gastric mucosa and renal
COX2: Inflammed tissues, brain and spinal cord
Why is there an increased risk of bleeding with MOTRIN?
It blocks both COX1 and COX2
How does celebrex work?
Only blocks COX2 (inflammed tissues, brain and spinal cord) so you still keep gastric mucosa safe.
Mechanism of action
Prostaglandins magnify ___ and ___ irritation to ___pathways
Magnify chemical and mechanical irritation to sensory pathways (so they do not cause pain on own, but magnify the pathway that does)
Prostaglandins ____level of cyclic AMP
Increase level of cAMP
Thromboxane is a _____. It stimulates ___ and is mostly present in ___ & ___
Vasoconstrictor, platelet aggregation, platelets & lungs
Prostacyclin is a ____. It ____ platelet aggregation. It is present in ____
Vasodilator, inhibits platelet aggregation, vascular endothelium
What is the most potent inhibitor of platelet aggregation?
High thromboxane with low prostacyclin can lead to ___ and ___
vasoconstriction and platelet aggregation. This will form blood clots
High prostacyclin with low thromboxane can lead to ___
Illoprost is an analogue of what?
Prostacyclin (potent inhibitor of platelet aggregation)
What drug may Illoprost be resistant to ?
Phenylepherine. Illoprost may produced hypotension resistant to Phenylepherine
What does prostaglandins do to blood vessels? What does it enhance the excretion of?
Vasodilation and enhance sodium excretion
What does prostaglandins do to inotropy?
DIRECT inotropic effects and can increase sympathetic nervous system activity
What effects does Thromboxane have on the pulmonary system? What drug may induce production of Thromboxane and have these pulmonary side effects?
1. Pulmonary vasoconstriction, pulmonary HTN, bronchoconstriction
What is the major site of prostaglandin synthesis?
Lungs and kidneys
What might prostaglandins do to bronchioles?
May cause bronchoconstriction OR bronchodilation
Why might asthma symptoms appear?
Imbalance thromboxane to prostacyclin ratio
___ are more potent bronchoconstrictors than ___
Leukotrienes > histamines
PGE2 and prostacyclin are made and released into circulation from kidneys causing ___ and ___. Prostacyclin causes ___ release from kidneys as well.
diuresis and decreased BP. Renin release
Misoprostol (Cytotec) is PGE1 analogue that improves renal function, decreases rejection in renal transplants. How is this drug effective in preventing ulcers in patients on NSAIDS?
It inhibits gastric acid
What two prostaglandins contract the uterus and are initiators and maintainers of labor?
PGE2 (Dinoprosterone) and PGF-2A (Dinoprost)
What is the theory of why preeclampsia occurs?
There is an imbalance in the ratio of thromboxane and prostacyclin in the placenta
What is increased in preeclampsia?
Production of thromboxane (why ASA is so effective in preeclampsia)
What do prostaglandins do to gastric acid secretion?
Inhibit gastric acid secretion