Topic 14 Flashcards
Plasma response to vascular injury: 1
Healthy, intact endothelium releases _____ into plasma
prostacyclin
Plasma response to vascular injury: 2
Prostacyclin binds to platelet membrane receptors, causing synthesis of
cAMP
Plasma response to vascular injury: 3
cAMP stabilizes inactive ______ receptors and inhibits release of granules containing ______ or _____
GP IIb/IIIa
platelet aggregation agents or Ca++
Plasma response to vascular injury: 4
Activated platelets cover/adhere to exposed ____ of damaged endothelium
subendothelial surface
Plasma response to vascular injury: 5
Activated platelets release what chemical mediators
Thromboxane A2
Serotonin
ADP
PAF
Plasma response to vascular injury: 6
Platelets are recruited to the ______
platelet plug
Plasma response to vascular injury: 7
After platelets go to the platelet plug- the chemical mediators that are bound to collagen from the subendothelium cause an increase in ____
Ca++ levels
Plasma response to vascular injury: 8
The elevated Ca++ causes what (3)
- release of platelet granules
- Activation of thromboxane A2 synthesis
- Activation of the GP IIb/IIIa receptors
Plasma response to vascular injury: 9
Fibrinolysis =
plaminogen –> plasmin —> Fibrin peptides
Plasma response to vascular injury: 10
formation of platelet fibrin plug =
prothrombin –> thrombin –> fibrinogen –> fibrin
Many functions mediated by aspirin’s ability to
irreversibly bind (and inactivate) the enzyme cyclooxygenase-1 (COX-1) and modify the activities of COX-2. •This inhibition lasts for the entire life of the platelet!!!
Aspirin inhibits (2)
- Platelets’ release of ADP is inhibited
2. Platelets’ ability to synthesize Thromboxane A₂ and Prostaglandin E₂ from Arachadonic Acid is inhibited
Aspirin: The Thromboxanes produced by platelets
tend to help induce _______ while the Prostaglandins tend to be ________.
clot formation
pro-inflammatory
Aspirin: COX-2 produces _____ once its been modified by aspirin.
lipoxins
– Lipoxins are anti-inflammatory
Aspirin: With Thromboxanes blocked, platelets won’t
aggregate for the life of the platelet (a good thing in places like coronary or carotid arteries!)
–RBC live for 100 days and platelets only live a week
Aspirin: With Prostaglandins blocked, inflammation (such
as occurs in arthritis) is _____, nerve endings’ thresholds for pain is _____, the anterior pituitary’s “thermostat” is _______
decreased
increased
reset at a lower level (hence aspirin’s antipyretic effect).
*These effects are all mediated through Prostaglandins
Aspirin side effects:
- bleeding
- GI (gastric ulcers)
- kidney damage
So while it helps prevent Transient Ischemic Attacks (TIAs) and embolic strokes, it can increase the incidence of
hemorrhagic strokes (particularly when given at high levels).
complete platelet inactivation occurs at a dose of
160 mg
Aspirin side effects (GI gastric ulcer)=
-PGI₂ prevents gastric parietal cells from secreting ___.
-PGE₂ and PGF₂-alpha cause the stomach
and SI to create
HCL
surface-protective mucus
*This happens on a cellular biochemical level, therefore things like “coated” and “enteric” aspirin don’t actually accomplish much!
Aspirin side effects (kidney damage)=
Prostaglandins are largely responsible for maintaining adequate renal blood flow.
-By blocking Prostaglandin synthesis:
salts and fluid start to be retained, potassium isn’t excreted properly, and the kidneys are “scarred” (interstitial nephritis.)
Aspirin Clearance: Conjugated by the ____, cleared by the ______ so the half-life is ______
liver
kidneys
3.5 hours
Aspirin Clearance: The conjugation stage is very
______, so at higher doses over several days the half-life increases ______.
•This increased half-life dramatically increases ______
saturable
4-5x
renal toxicity causing a vicious cycle
Aspirin: other drug name
Acetylsalicylic Acid
