Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
Define Hemostasis
|
- Hemostasis = cessation of blood loss from a damaged vessel
- Primary Hemostasis = platelet aggregation - Secondary Hemostasis = coagulation |
|
Regulation of Hemostasis
|
- 2 systems regulate blood coag and thrombus formation:
(i) Fibrin Inhibition - plasma contains protease inhibitors that inactivate the coagulation proteins (ii) Fibrinolysis - inactive plasminogen is converted to proteolytic enzyme plasmin --> digests fibrin |
|
Drugs used to reduce clotting: Platelet aggregation inhibitors
|
- decrease synthesis or action of chemical signals that promote platelet aggregation
- include: Cyclooxygenase inhibitors ADP Receptor blockers Phosphodiesterase inhibitors Blockers of platelet GP IIb/IIIA receptors |
|
Cyclooxygenase inhibitors
|
ASPIRIN
- inhibits thromboxane A2 synthesis by irreversible acetylation of enzyme COX - thromboxane A2 causes platelets to degranulate and to aggregate - b/c platelets dont have a nucleus, they cant synthesize any new proteins during its 10-day lifetime |
|
Cyclooxygenase inhibitors - Aspirin - Uses
|
- prophylactic tx of transient cerebral ischemia
- reduce incidence of recurrent MI - decrease mortality in post MI pts |
|
ADP Receptor blockers
|
CLOPIDOGREL & TICLOPIDINE
- irreversible inhibitors of P2Y12 (subtype of ADP receptor on platelet surface) - clopidogrel has less AE and is preferred over ticlopidine |
|
Phosphodiesterase inhibitors
|
DIPYRIDAMOLE
- coronary vasodilator - prophylactically treat angina pectoris - inc cAMP by inhibiting phosphodiesterase and/or by blocking uptake of adenosine, which acts at A2 receptors to activate adenylyl cyclase |
|
Phosphodiesterase inhibitors - Dipyridamole - Uses
|
- by itself has little use
- used in comb w/ warfarin for thromboemboli in pts w/ prosthetic heart valves - used in comb w/ aspirin for secondary prophylaxis of cerebrovascular disease |
|
Blockers of Platelet GP IIb/IIIA Receptors
|
- used in pts w/ acute coronary syndromes
- IIb/IIIa complex = receptor for fibrinogen, vitronectin, fibronectin, and vWF - activation of this receptor = final common pathway for platelet aggregation |
|
Blockers of Platelet GP IIb/IIIA Receptors - Drugs
|
ABCIXIMAB
- Monoclonal Ab directed against human GP IIb/IIIa receptor EPTIFIBATIDE - cyclic peptide reversible antagonist of the GP IIb/IIIa receptor TIROFIBAN - nonpeptide reversible antagonist of the GP IIb/IIIa receptor |
|
Drugs used to reduce clotting: Anticoagulants
|
- Unfractionated Heparin and low-molecular wt Heparins
- Selective Factor Xa Inhibitors - Direct Thrombin Inhibitors (DTIs) - Coumarin anticoagulants |
|
Heparin - General info
|
- Injectable, rapidly acting anticoag. often used acutely to interfere w/ formation of thrombi
- mix of straight-chain anionic glycosaminoglycans |
|
Heparin - MOA
|
- Usually, antithrombin III (an alpha-globulin) inhibits serine proteases, including several clotting factors like thrombin
- In absence of heparin, antithrombin III interacts w/ thrombin very slowly - binding of heparin to antithrombin III allows antithrombin to rapidly inhibit thrombin EXCEPT that already bound to fibrin |
|
Low-molecular-weight Heparin (LMWH)
|
- inhibits activated factor X
- less effect on thrombin than UFH |
|
Monitoring of Heparin
|
- done by activated partial thromboplastin time (aPTT) assay
- aPTT = test of integrity of intrinsic and common pathways of coagulation - LMWH has higher therapeutic index than unfractionated heparin especially when used for prophylaxis (not necessary to monitor LMWH levels) |
|
Heparin - AE
|
- Bleeding
- Hypersensitivity rxns - Thrombosis (b/c reduced antithrombin III activity) - Heparin-induced Thrombocytopenia (HIT) Type II |
|
Heparin-induced Thrombocytopenia (HIT) Type II
|
- Ab recognize complexes of heparin and a platelet factor 4 --> platelet aggreg and release of platelet contents
- can result in thrombocytopenia and thrombosis - therapy = discontinue heparin and admin of a DTI or fondaparinux |
|
Reversal of Heparin Action
|
- discontinuance
- if bleeding: protamine sulfate given |
|
Selective Factor Xa Inhibitors
|
FONDAPARINUX
- pentasaccharidde - sequence of 5 carbs necessary for binding to antithrombin III - specific inhibitor of Xa - negligible antithrombin activity - tx of DVT |
|
Direct Thrombin Inhibitors (DTIs)
|
- directly bind to active site of thrombin
- include: LEPIRUDIN BIVALIRUDIN ARGATROBAN |
|
Lepirudin
|
- hirudin = specific thrombin inhibitor from the leech!
- available in recomb form as lepirudin - action independent from antithrombin III - monitored by aPTT - NO antidote exists |
|
Bivalirudin
Argatroban |
Bivalirudin = synthetic derivative of hirudin
Argatroban = small molecule thrombin inhibitor |
|
Coumarin anticoagulants
|
WARFARIN and DICUMAROL
- called oral anticoags b/c unlike heparin they are given orally |
|
Warfarin and Dicumarol - MOA
|
- inhibit vit K epoxide reductase --> prod of inactive clotting factors (lack gamma-carboxyglutamyl side chains)
- takes 8-12 hrs - can be overcome with vit K (24 hrs) |
|
Monitoring Warfarin levels
|
- narrow TI; many drug-drug interactions
- monitoring performed w/ the prothrombin time (PT) - test of extrinsic and common pathways of coagulation - warfarin prolongs PT (b/c it dec amt of functional factor VII) |
|
Warfarin and Dicumarol - AE
|
- Hemorrhage
- Cutaneous necrosis w/ reduced activity of protein C - Warfarin crosses the placenta - Warfarin should NEVER be admin w/ pregnancy |
|
Drugs used to reduce clotting: Thrombolytics (fibrinolytics)
|
- lyse thrombi by catalyzing conversion of plasminogen --> plasmin
- reduce mortality of acute MI STREPTOKINASE UROKINASE ALTEPLASE, RETEPLASE, & TENECTEPLASE ANISTREPLASE |
|
Drugs used to treat bleeding
|
- plasminogen activation inhibitors
- protamine sulfate - vitamin K - plasma fractions |
|
Plasminogen activation inhibitors
|
AMINOCAPROIC ACID
- inhibits plasminogen activation |
|
Protamine sulfate
|
- antag of heparin
- high in arginine - forms complex w/ heparin with no anticoagulant activity - inactive against fondaparinux |
|
Vitamin K
|
- can stop oral anticoags
- 24 hrs - if immediate hemostasis needed, fresh-frozen plasma should be infused |
|
Plasma Fractions
|
- Def in plasma coag factors can cause bleeding
- Factor VIII deficiency (classic hemophilia, or hemophilia A) and factor IX def (Christmas disease or hemophilia B) account for most of the heritable coagulation defects |