Regal- Thrombolytics, Anticoagulants, and Antiplatelet Drugs Flashcards
When do we interfere w/ hemostasis?
Prevent and treat thrombosis
- Venous thrombosis
- Arterial thrombosis–platelet activation is central
What agents do we use to control blood fluidity?
Antiplatelet agents
Parenteral anticoagulant heparin and its derivatives (Thrombin inhibitors direct/indirect)
Oral Coumadin anticoagulants (inhibitors of vit K)
Fibrinolytic agents to lyse pathological thrombi
What does aspirin do mechanistically?
It is an irreversible inhibitor of COX
Do platelets have Cox2?
NO
Can platelets make more COX
NO they don’t have a nucleus
What does aspirin do clinically?
Antipyretic, analgesic, anti-inflamatory
What are the adverse effects of aspirin?
Bleeding
GI disturbances
Tinnitus
What is the difference between low and high doses of aspirin?
LOW- antiplatelet
HIGH- inhibits COX1 and 2 in epithelial cells (anti-inflammatory)
What are the three ADP receptor antagonists?
Clopidogrel
Ticlopidine
Prasugrel
How do ADP antagonists work?
Irreversible ADP receptor antagonists that prevent activation of ADP receptor that would ultimately lead to platelet aggregation
How long do ADP receptor antagonists last?
days
When are ADP receptor antagonists commonly used?
Stenting
Recommended for pts that don’t tolerate aspirin
What are the adverse effects of ADP receptor antagonists?
BLEEDING
nausea, diarrhea, rash
severe leukopenia
TTP (very rare–ticlodipine)
Which ADP R Antag has the worst side effects?
Ticlodipine
Which ADP drug requires activation?
Clopidogrel via CYP2C10
**drugs that impair this isoform should be used w/ caution (omeprazole)
What does dipyridamole do?
Increases cAMP and inhibits platelet activation by inhibiting PDE3 (preventing the break down of cAMP) and inhibiting platelet uptake of adneosine, thus increasing adenosine interaction w/ adensoine receptor and increasing cAMP
PDE 3 inhibitor
What adverse effect is associated w/ dipyridamole?
Headache
b/c it’s a vasodilator
How is dipyridamole commonly prescribed? Why?
In combination w/ aspirin or warfarin
No beneficial effect by itself
What do GPiiB/IIIa receptor inhibitors do?
Prevent binding of adhesive glycoproteins such as fibrinogen and vWF to activated platelets
How do abciximab, eptifibatide and tirofiban differ?
abciximab-Humanized MAB a against receptor
eptifibatide- fibrinogen analoguse
tirofiban- non-peptide competitive inhibitor
What are the three GPIIb/IIIa receptor inhibitors?
abciximab
eptifibatide
tirofiban
What is the one disadvantage of GpIIb/IIIa receptor inhibitors?
they have to be given IV
What are GpIIb/IIIa receptor inhibitors commonly used for?
w/ aspirin and heparin during angioplasty
for acute coronary syndromes
What are the adverse effects of GpIIb/IIIa receptor inhibitors?
Bleeding
thrombocytopoenia
What are the two types of thrombin inhibitors?
Direct and indirect?
What are the 4 types of direct thrombin inhibitors?
Lepirudin
Bivalirudin
Agratroban
Dabigatran (ORAL)
What are the three types of indirect thrombin inhibitors?
Unfractionated heparin
LMW heparin
Fondaparinux
What do lepirudin, bivalirudin and argatroban and dabigatran do? How is dabigatran different?
bind directly to thrombin and inhibit the enzyme
dabigatrin is ORAL
Which indirect thrombin inhibitors interact w/ antithrombin and enhance/accelerate its inactivation of Factors Xa?
Heparin
LMWH
Fondaparinux
Which indirect thrombin inhibitors enhance/accelerate antithrombin’s inactivation of thrombin (IIa)?
Heparin and LMWH
What is the end effect of indirect thrombin inhibitors?
Factor Xa and thrombin IIa don’t work so clotting doesn’t happen
Unfractionated heparin requires close monitoring of…?
aPTT–activated partial thromboplastin time
Does LMW heparin require monitoring?
No, it has more predictable pharamacokinetics
What are the adverse effects of indirect thrombin inhibitors?
Bleeding
Heparin induced thrombocytopenia
What causes Heparin induced thrombocytopenia?
Probably the development of IgG antibodies against complexes of heparin w/ platelet factor 4
**twice as likely in women than men
Which indirect thrombin inhibitors only targets Xa?
Fondaparinux
Which indirect thrombin inhibitors has no antidote effect?
Fondaprinux
LMWH has only parital
Heparin is full
What does protamine do?
Combines w/ negatively charged heparin to form a stable complex that lacks anticoagulant activity
What does protamine do to LMWH?
incompletely reverses its activity
What are the two oral anticoagulant drugs?
Warfarin
Vitamin K
What does Warfarin do?
Inhibits conversion of oxd vit K epoxide into it’s reduced form, vit K hydoquinone>
this inhibits vit K dependent gamma carboxylation of factors II, VII, IX and X and Prot C
What’s important to know about the pharmakokinetics of warfarin?
Delayed hypothrombic effect
narrow TI–need enough so that you don’t clot and not enough that you don’t bleed all over
What are the adverse effects of warfarin?
Bleeding
flatulence and diarrhea
cutaneous necrosis
chondrodysplasia
What is the difference between R and S warfarin and which is the more active enantiomer?
S is more active enantiomer
S- metabolized by cyp2c9
R- metabolized by cyps1a1, 1A2, 3A4
What is one of the worst things about warfarin?
It interacts with MANY drugs
What are the effects of warfarin pharmacokinetically?
Inhibition of cyt450
Metabolism-> more warfarin
Decreased plasma protein binding
What are the effects of increased warfarin on pharmacodynamics?
decreased platelet/clotting factor function
Decreased availabilty of vit K–>warfarin increases
What are the effects of decreased warfarin pharmacokinetically and pharmacodynamically?
pharmacokinetically- induction of CYT p450 metabolism, decreased absorption
pharmacodynamically- increased clotting factor/vit K concentrations
What do you do if a pt has been given TOO much warfarin and is bleeding uncontrollably?
STOP the drug
Add vit K–so enzyme can do it’s thing and make the right clotting factors (phytonodione)
What are urokinases?
kidney enzymes that directly converts plasminogen to plasmin
What are the three tPAs?
Alteplase
reteplase
tenecteplase
What do tPAs do?
Preferentially activate plasminogen that is bound to fibrin which confines it to the thrombus rather than systemic activation.
What do Fibrinolytic Drugs do?
Dissolve EXISTING life threatening thrombi
activate plasminogen
How are fibrinolytic drugs given?
IV
Narrow spectrum of use
What are the adverse effects of fibrinolytic drugs?
Bleeding
cost
What is the MOA of alteplase, reteplase, tenecteplase?
Selective activation of fibrin bound plasminogen
