Autocoids Flashcards
Eicosanoids are synthesized in response to which kind of stimuli
IgE reactions inflmmmatory mediators trauma toxins heat
Eicosanoids act via which method of signal tranduction
G-protein coupled receptors
Membrane phospholipds are broken down to arachidonic acids by which enzyme
phosphoplipase A2
What is the function of phosphoplipase A2
Breaks down membrane phospholipids into arachidonic acid
Which 2 enzymes break down arachidonic acid?
Cyclooxygenase
Lipoxygenase
The reaction of Cyclooxygenase and Lipoxygenase produces which 2 molecules
Endoperoxides and Hydroperoxides
Cyclooxygenase and Lipoxygenase act on which molecule
Arachidonic acid
Which inflammatory mediators are derived from Endoperoxides
Prostaglandins and thromboxane A2
Prostaglandins and thromboxane A2 is derived from which molecule directly
Endoperoxide
Which inflammatory mediators are derived from Hydroperoxides
Leukotrienes
Leukotrienes are derived from which molecule directly
Hydroperoxide
Which group of drugs inhibit phospholipase A2
glucocorticoids
Which group of drugs inhibit cyclooxygenase
NSAIDs
Which drugs is a selective inhibitor of COX 2
Celecoxib
Which drug is an inhibitor of lipoxygenase
Zileuton
Which drugs inhibits leukotrienes
Zafirlukast
What is the mechanism by which the drug Zafirlukast inhibits leukotrienes
It antagonizes the receptor for leukotrienes
Zileuton and Zafirlukast inhibits the production of leukotriene in the treatment of which condition
Asthma
What is the action of leuktrienes A4, C4 and D5
bronchoconstriction
vasodilation
Which product from endoperoxides are needed for platelet aggregation
Thromboaxane A2
A product of endoperoxides responsible for pain, swelling, fever and renal vasodilation
PGE2
Which prostaglandins are necessary for maintenance of GI mucosa
PGE2 and PGI2
Which cyclooxygenase is constitutively expressed
COX1
Which COX is necessary for protecting GI mucosa and platelet aggregation
COX1
Which COX is necessary for making the inflammatory prostaglandins
COX2
Which COX is necessary for platelet stabilization
COX2
COX2 aid in platelet stabilization by allowing the production of which arachidonic acid derivative
Prostaglandin I2 (prostacyclin)
Another name for prostacyclin
Prostaglandin I2
Misoprostol is the synthetic version of which arachidonic acid derivative
PGE1
Which drug is an identical form of the naturally occurring PGE1
Alprostadil
What is the contraindication of using Alprostadil during pregancy
Can cause uterine contraction
What is misoprostol used for?
What is the mechanism of its action
Treat NSAID induced gastric ulcers
- it is a synthetic version of PGE1, which maintains the gastric mucosa
What are 2 uses of alprostadil?
What is the mechanism of its action
Maintains patency of ductus arteriosus
- it is identical to PGE1 which dilates vascular smooth muscle
Aids erectile dysfunction
-vasodilation
Which drug is a version of PGE2 and what is it used for
DInoprestone
- cervical ripening and abortifacient
Carboprost is a version of which prostaglandin?
- what is its use
PGF2 alpha
- abortifacient
Latanoprost is a version of which prostaglandin?
- what is its use
PGF2 alpha
-glaucoma by reducing intraocular pressure
Which drug, that is a synthetic version of PGI2 is used to treat pulmonary hypertension
Epoprostenol
Which 2 derivatives of endoperoxide have opposing effects on platelets
Thromboxane A2
PGI 2
Thromboxane A2 works via which signal transduction pathway
Gq
PGI 2 works via which signal transduction pathway
Gs
Platelet stabilization is done by which prostaglandin
PGI 2
Cyclooxygenases are irreversibly inhibited by which drug
Aspirin
High does of aspirin has what effect on uric acid elimination
decreases tubular reabsorption which leads to uricosuria
How is the occurrence of gout possible while taking low doses of aspirin
low doses of aspirin decreases renal tubular secretion of uric acid, leading to hyperurecemia
What kind of respiratory acid/bases condition is seen in high vs. toxic doses of aspirin
why?
High does: respiratory alkalosis because it increases resp rate which lower pCO2
Toxic doses: respiratory acidosis because it inhibits the resp. center leading to high pCO2
What is the underlying mechanism of gastritis seen in NSAID use
Inhibition of PGE2 which is needed to maintain the gastric mucosa
What physical symptoms are seen in salicylism
tinnitus
vertigo
decreased hearing
Why is bleeding time increased why on NSAIDs
Inhibition of COX1, leads to inhibition of thromboxane A2 production which is needed for platelet aggregation
What is the triad seen in aspirin hypersensitivity
asthma
nasal polyps
rhinitis
What clinical symptoms is seen when aspirin is taken with alcohol
GI bleeding
How does aspirin affect the use of warfarin
Warfarin’s effect is increased (possible toxicity)
How does aspirin affect the use of uricosurics
decreases its effect
Three treatments for aspirin toxicity
Gastric lavage
activated charcoal
Alkalizing the urine (eg. sodium bicarb)
What is the use of the drug ketorolac
analgesic
What is the use of the drug indomethacin
-what is the mechanism of action
Closure of ductus arteriosus by inhibiting COX, so PGE2 cannot be made
Why would increased serum creatine be seen in someone using an NSAID
NSAID inhibit the production of prostaglandins which vasodilate the afferent arteriole of the kidney
What kind of drug is celecoxib
Selective COX 2 inhibitor
Why would less antiplatelet action and less GI toxicity be seen in someone using celecoxib
Celecoxib is a COX2 inhibitor. COX1 is necessary for making PGE2 and TXA2 which re needed for GI mucosa and platelet aggregation respectively.
Why is there an increased risk for MIs and stroke while on celecoxib
celecoxib is a COX2 inhibitor which is need to make PGI2 (prostacyclin) which stabilizes platelets
This drug acts on CNS cyclooxygenases only
Acetaminophen
How can chronic alcohol increase liver toxicity while on acetaminophen
Chronic use of ethanol enhances liver
toxicity via induction of P450, which results in formation of a reactive metabolite (N-acetylbenzoquinoneimine), usually inactivated by glutathione
(GSH). In overdose situations, the finite stores of GSH are depleted causing the metabolite to react even more with hepatocytes
Which NSAID has the highest antithrombotic effect
aspirin
