Flashcards in platelet blockers Deck (51):
the enzyme cyclooxygenase-1 (COX-1) and modify the activities of COX-2.
• This inhibition lasts for the entire life of the platelet!!!
since aspirin inhibits cox1 and 2
latelets’ release of ADP is inhibited
– Platelets’ ability to synthesize Thromboxane A2 and Prostaglandin E2 from Arachadonic Acid is inhibited.
thrromboxanes and prostaglandins
The Thromboxanes produced by platelets tend to help induce clot formation while the Prostaglandins tend to be pro-inflammatory.
lipoxins once its been modified by aspirin. Lipoxins are anti- inflammatory.
With Thromboxanes blocked
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???
dont have a nucleus
With Prostaglandins blocked, inflammation
(such as occurs in arthritis) is decreased, nerve endings’ thresholds for pain is increased, the anterior pituitary’s “thermostat” is reset at a lower level (hence aspirin’s antipyretic effect).
four clinical apps for aspirin
anti inflammatory, anti platelet, anti arthritic, anti pyrrittic or fever
since platelets cant aggregate cuz of aspirin it reduces
acute MI, thrombotic stroke,DVT, and pulmonary emboli
side effects of aspirin #1
#1 bleeding (hemmorhagic strokes at high doses)
complet platelet inactivation occurs at
side effect #2 of aspirin
GI (such as gastric ulcers) -PGI2 prevents gastric parietal cells from
-PGE2 and PGF2-alpha cause the stomach and SI to creative surface-protective mucus.
*This happens on a cellular biochemical level, therefore things like “coated” and “enteric”
aspirin don’t actually accomplish much!
aspirin side effect #3
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.)
Conjugated by the liver, cleared by the kidneys so the half-life is 3.5 hours.
• The conjugation stage is very saturable, so at higher doses over several days the half- life increases 4-5X.
• This increased half-life dramatically increases renal toxicity causing a vicious cycle.
Like aspirin: Block platelet aggregation Unlike aspirin: Different M.O.A. All act by irreversibly inhibiting the ADP pathway of platelets..• This blocks platelets’ GP IIb/IIIa receptors.
• Consequently, affected platelets can’t bind to each other or to fibrinogen.
(ticlid) thyenopydine Approved for use in the prevention of TIAs and strokes
• Approved for use with aspirin post-stent placement to prevent thrombi formation
ticlopidine black box warning
– Aplastic anemia – Neutropenia – Thrombotic Thrombocytopenia Purpura
(plavix) thyenopydine Like Ticlopidine, but less side effects (although thrombotic thrombocytopenia purpurea still can occur).
• Used more for cardiac “issues” (MI prevention, ACS, post-PTCA etc.) than Ticlopidine.
(effient) thyenopydine. The GOOD news:
-Prasugrel’s is more effective in treating thrombotic-related events than the other thienopyridines!
⦁ The BAD news:
-Black Box Warning for hemorrhagic stroke, excessive hemorrhage, and negative sequelae resulting from sudden discontinuation of Prasugrel therapy.
used to monitor thyenopydines AND Antiplatelet Therapy Resistance
Glycoprotein IIb/IIIa Blockers USES
All given parenterally
• All used extensively for ACS and in cath labs to make your life more miserable when they finally decide to send the patient to surgery.
Glycoprotein IIb/IIIa Blockers DRUGS
Abciximab (Reopro) - Eptifibatide (Integrilin) - Tirofiban (Aggrastat)
Dypridamole how it works and used
(persantine) primarily used as a coronary vasodilator • Blocks cyclic AMP (cAMP) which
is a ubiquitous intracellular “messenger” chemical derived from that ubiquitous cellular energy currency, ATP.
dypyridamole end result
After a chain of intracellular miracles, Thromboxane A2 synthesis is blocked (no prostaglandin effect).
-Rarely (if ever)
sed by itself.
-Typically used as an adjunct with warfarin or aspirin for anticoagulation post-prosthetic heart valve implantation or for a-fib.
heavily- branched complex glucose-based polymers.
• Used as a
volume expander (particularly when albumin is unavailable!)
Besides acting as a volume expander/blood viscosity reducer it has anti-thrombotic functions that are sort of ill-defined.
• Dextrans bind RBCs, platelets, and vascular endothelium making them all less “sticky”.
• Decreases Factor V, VIII, and IX functionality.
• Clots formed in the presence of dextrans are “less sturdy” and more easily lysed.
One gram of dextran binds 20-25 ml of H2O.
dextran side effect
#1) Intra-op and post-op bleeding.
#2) Volume overload, particularly in heart failure (why?) and anuric renal failure patients.
#3) Anaphylaxis is not uncommon and occurs within minutes of administration!
macrodex bigger osmotic effect than 40
by kidneys over several hours
Dextrans max dosage
*MAXIMUM 2g/kg (20ml/kg)
Like Dextrans, but made with a mixture of starch polymers instead of glucose polymers.
• A volume expander like Dextran. • Significantly reduces Factor VIII causing
elevated aPTT values
• Hespan usage is associated with acute renal failure, coagulopathies, and anaphylaxis.
Cleared similarly to Dextrans but has a real tendency to “hand around”.
• Hespan is found in the plasma months after administration.
max daily hespan dose
Maximum daily dosage listed as 20ml/kg
*...but this seems to be more dogma than evidence-based.
• Alteplase/tPA: (Activase) • Reteplase(Retavase) • Streptokinase (Streptase) • Urokinase(Kinlytic)
thrombolytic drugs on bypass
*Unlike all the anticoagulants thrombolytics
hese drugs actually dissolve (“lyse”) clots that are already present in a critter.
• Not really an enzyme,
Streptase. but attaches to plasminogen and this complex acts to convert plasminogen into plasmin.
• This complex also destroys fibrinogen and Factors V and VII
streptokinase used for
pulmonary emboli(might not work cuz of shunts), DVTs, aMIs, and thrombosed shunts
streptokinase half life
less than 30 minutes
streptokinase monitored by
thrombin time from bugs
urokinase half life and what it does
Kinlytic. Directly converts plasminogen into plasmin to dissolve clots.
• Very short half life (~20 minutes) • Approved for use in pulmonary emboli • Made from urine (well, it could be...)
Activase.naturally occurring enzyme from human cancer cells, tPA selectively and directly binds with plasminogen that is bound to fibrin (as in a clot.)
• In low doses, free plasminogen is hardly affected but bound fibrinogen is selectively targeted, so you get more clot lysis and less diffuse hemorrhagic problems as compared to streptokinase.
alteplase used for/half life
aMIs, thombotic strokes, and pulmonary embolism.
• Very short half-life (5-30 minutes)
Retavase. A synthetic close-relative of tPA. • Cheaper than tPA. • Less fibrin-specific than tPA.
AT 3 half life
types of AT 3
1) Made from pooled human plasma
and called Thrombate*
2) Made from the milk of genetically modified goats (I’m not making this up!) and called Atryn.
*Other major differences:
-Atryn is ~40% cheaper to use than Thrombate.
-Atryn’s half-life is ~9 hours vs. Thrombate’s ~3 days.
-Atryn must be refrigerated, Thrombate’s stored at room temperature.. TREND TOWARDS ATRYN