Exam 3; Agents that Affect the Clotting System Flashcards
The initial activation of platelets leads to what
platelet plugs
When ADP binds to the platelets, they activated what
glycoprotein receptors
GPIIb and GPIIIa
This binds to GPIIb and GPIIIa and leads to platelet aggregation
fibrinogen
This inhibits platelet aggregation
cAMP
The clot consist primarily of what
fibrin
All of the clotting factors are circulating proteins, and when activated become what
proteolytic enzymes
What does Xa stimulate
prothrombin to thrombin (IIa)
What two things does thrombin stimulate
fibrinogen to fibrin
activates platelets, factors VII, VIII, XIII
What is the purpose of fibrinogen
cross-linkning platelets
What is the purpose of fibrin
to form the clot
What does XIII to XIIIa assist in
stabilizing the clot
Which factors require Ca to work
XI to XIa X to Xa prothrombin to thrombin fibrinogen to fibrin XIII to XIIIa
What are the steps to reverse clot formation
plasminogen → plasmin → clot lysis
What is the step to localize clotting
antithrombin III → causes inactivation of thrombin, factors IX, X, XI, XII
This is a genetic disorder that causes inadequate clotting
hemophilia
Which is more common, too little clotting or too much clotting
too much clotting
This is a clot that adheres to a blood vessel wall
thrombus
What is it when there is a thrombus in the arteries
white thrombi
What is a white thrombi associated with
atherosclerotic plaques
What is it when there is a thrombus in the veins
red thrombi
What is a red thrombi associated with
pooling of blood in the extremities
This is when a thrombus breaks off and travels through the blood stream; it will stop one it can no longer fit through the vessels clogging it
thromboembolus
In which four conditions are anti-coagulates are used
thromboembolic disease
after most kinds of surgery
during transfusions
in patients with heart disease
What are the three calcium chelators anti-coagulates
Citric acid
EDTA
EGTA
Why do you generally not give people calcium chelators
due to Ca being widespread-ly used in the body; unless hypercalcemia
This anti-coagulate is not synthetic and is purified from animal tissues with a strong negative charge
heparin
What is the mechanism behind heparin
binds to anti-thrombin, a protease inhibitor
At low doses, what does heparin do
inhibits Xa
thus decreasing the formation of thrombin
At high doses, what does heparin do
inhibits thrombin, IXa, IXa, and XIIa
After thrombin is inactivated, heparin does what
is released and moves on to catalyze another reaction
True or False
Heparin is able to lyse existing clots
False; it is not
Heparin must be given by which method
Injection; usually subQ
Why can heparin not be given orally
It is such a large molecule that is will not be absorbed by the gut
True or False
Heparin easily passes the placenta and can cause major damage to the fetus
False; it cannot pass the placenta
What is the half life of heparin
1 hour; immediate onset
What degrades heparin
Heparinase
What is the dose response of heparin
It is somewhat unpredictable because it can bind to a variety of proteins
What is the toxicity level of heparin
Relatively non-toxic
Major toxicity is bleeding
What can be used to treat an overdose of heparin
Strongly positive protnine sulfate
What three things can result from long term use of heparin
Osteoporosis; due to lack of osteoclasts
Thrombocytopenia; loss of platelets
Hypersensitivity; because it is an animal product
What are two low molecular weight heparins
Enoxaparin
Dalteparin
What is the half live of enoxaparin and dalteparin
4 hours; longer than heparin
Which molecule does enoxaparin and dalteparin have more of an effect on, Xa or thrombin?
Xa
What are some differences between enoxaparin/dalteparin and heparin
less osteoproosis and HIT
more predictable dose response
more expensive
not readily reversed by protiminie sulfate
What is a side effect of enoxaparin and dalteparin
may cause spinal hematoma in patients who have had a spinal tap or spinal anesthesia
This is a purely synthetic heparin-like drug with a half life of 17hrs, given subQ
fondaparinux
What is the mechanism of fondaparinux
works only on factor Xa
The saliva of a leech contains this drug
hirudin; anticoagulate
What is the mechanism of hirudin
works by directly inhibiting thrombin
These are two synthetic analogs of hirudin
bivalirudin
desirudin
This is a peptide derived from hirudin
agratroban
When are the analogs of hirudin used
when the patient has heparin induced thrombocytopenia
What is the mechanism of warfarin
inhibition of the enzyme that allows vitamin K to be recycled
K-oagulation
What is vitamin K essential for
synthesis of factors VII, IX, X, and pro-thrombin
What is warfarin metabolized by
P450
can be affected by other drugs and grapefruit juice
What are three toxicities of warfarin
many drug interactions
hemorrhage
can pass the placenta (cat. X)
This is a pro-drug that is a direct thrombin inhibitor (enzyme inhibitors)
diabigatran
What are two factor Xa inhibitors (enzyme inhibitors)
rivaroxaban
apixaban
This is a thrombin receptor blocker
vorapaxar
In which type of patient do you need to be care administrating vorapaxar to
patients with a history of intracranial bleeding
What are four ADP inhibitors (inhibits ADP from binding to receptor)
ticlopidine
clopidogrel
prasugrel
ticagrelor
This ADP inhibitor can cause neutropenia and agranulocytosis
ticlopidine
What is the main difference between all the ADP inhibitors
pharmacokinetics
These are three fibrinogen receptor inhibitors
abciximab
tirofiban
eptifibatide
The fibrinogen inhibitors prevent what
platelet aggregation
The fibrinogen inhibitors can cause what
thrombocytopenia
Which method are the fibrinogen inhibitors given
IV
This is a COX inhibitor which inhibits thromboxane synthesis via cyclooxyrgenase inhibitor (enzyme inhibitor)
aspirin
What are two phosphodiesterase inhibitors
cilostazol
dipyradiamole
What is the mechanism behind cilostazol and dipyradiamole
inhibits the enzyme that breaks down cAMP (phosphodiesterase)
This drug decreases platelet formation, maturation, and number; decreasing platelet count
anagrelide
What are three contradictions for oral anti-coagulants
anyone with a bleeding disorder
severe hypertension
after surgery in the eye, brain, or spinal cord
Why is anyone with a bleeding disorder, contraindicative of oral anti-coagulants
could have a hidden bleeding disorder; 25% of all deaths due to GI bleeding were because they didn’t know it
Why is anyone with hypertension, contraindicative of oral anti-coagulants
small vessels are damaged and if you remove the clotting mechanism then you will “sprout leaks”
What are three agents that dissolve formed clots
streptokinase
urokinase
tissue plasminogen activator
What is the mechanism behind streptokinase, urokinase, and tissue plasminogen activator
converts plasminogen to plasmin
plasmin hydrolyzes fibrin and degrade what
fibrinogen and factors V and VII
When will you use the agents that dissolve formed clots
if someone ocomes into the hospital having a heart attack due to a clot; given IV
What is the mechanism behind hemostatic agents
inhibits plasminogen activation (enzyme inhibitor)
What are the two hemostatic agents
aminocaproic acid
tranexamic acid
