Flashcards in Pharm 14- Platelet Inhibitors, Thrombolytics, AT-III Deck (80)
Many functions are mediated by what ability of aspirin?
Irreversibly bind (and inactivate) the enzyme cyclooxygenase-1 (COX-1) and modify the activities of COX-2; inhibition lasts for the entire life of the platelet
How does aspirin affect platelets?
Platelets release of ADP is inhibited
Ability to synthesize Thromboxane A2 and Prostaglandin E2 from Arachadonic Acid is inhibited
What do the thromboxanes produced by platelets do?
Tend to help induce clot formation while the prostaglandins tend to be pro-inflammatory
What does COX-2 produce once its been modified by aspirin?
Lipoxins; once its been modified by aspirin
What's the effect of Lipoxins?
What does the blocking of thromboxanes do to platelets?
Platelets won't aggregate for the life of the platelet (a good thing in places like coronary or carotid arteries)
Why don't platelets just make more thromboxane?
They don't have a nucleus so they are unable to make more. Once you have it commited and already programmed
RBCS live how long
How long to platelets live?
About a week
What is the effect of having prostaglandins blocked?
Nerve endings' thresholds for pain is increased
Anterior pituitary's thermostat is reset at a lower level (hence the aspirin's antipyretic effect)
What are the four major clinical applications for aspirin?
Aspirin Side Effects
Bleeding (Hemorrhagic strokes)
GI (such as gastric ulcers)
What does aspirin help prevent?
At what dose of aspirin does complete platelet inactivation occur?
Why does aspirin have GI effects (such as gastric ulcers)?
PGI2 prevents gastric parietal cells from secreting HCL
PGE2 and PGF2-alpha cause the stomach and SI to create surface-protective mucus
Aspirin thins the layer of slime becuase it produces more acid and stomach is exposed to the effects of the acid
Why don't "coated" and "enteric" acid actually accomplish much?
GI effects occur on cellular biochemical level
Why does aspirin have a kidney damaging side effect?
Prostaglandins are largely responsible for maintaing adequate renal blood flow; by blocking prostaglandin synthesis salts and fluid start to be retained, K+ isn't excreted properly and the kidneys are scarred "Interstitialneprhritis"
What does PGF2-alpha do?
Massive uterine contractions
How is aspirin cleared?
Conjugated by the liver, cleared by the kidneys
What is the half-life of aspirin?
What happens to the half-life of aspirin as higher doses are given?
Conjugation stage is very saturable
Higher doses over several days the half-life increase 4-5x; increased half-life dramatically increases renal toxicity causing a vicious cycle
How are Thienopyidines like and unlike aspirin?
Like aspirin: Block platelet aggregation
Unlike aspirin: different MOA
What are some examples of Thienopyridines?
How do Thienopyridines work?
Irreversibly inhibit the ADP pathway of platelets
Blocks platelets GP IIb/IIA receptors
Affected plts cant bind to each other or fibrinogen
When is Ticlopidine (Ticlid) approved for use?
Prevention of TIAs and strokes
With aspirin post-stent placement to prevent thrombi formation
What is the black box warning for Ticlopidine (Ticlid)?
Thrombotic Thrombocytopenia Purpura
Thrombotic Thrombocytopenia Purpura
Rash; platelets get used up, purple blotches because of the thrombi
Clopidogrel (Plavix) Use
used for more cardiac "issues" (MI prevention, ACS, post-PTCA) than Ticlopidine (Ticlid)
How does Clopidogrel (Plavix) compare to Ticlopidine (Ticlid)?
Like it, but less side effects
Although thrombotic thrombocytopenia purpurea can still occur