Drugs in the blood Flashcards
four stages of hemostasis and what happens during them
i. Vasospasm (vasoconstriction)
-Immediate; restricts blood flow
-Sympathetics and local factors eg. thromboxane
-Myogenic properties of vessel wall
ii. Platelet response
-Within seconds; forms initial plug
-Platelets adhere to exposed collagen of damaged endothelium, and each other
-Platelet plug releases chemical mediators (TXA2, 5-HT and ADP)
(recruit more platelets, promote vasoconstriction, initiate the coagulation cascade)
ii. Coagulation Phase
-Occurs thru sequential conversion of inactive proteins into catalytically active proteases
-Tissue factor-factor VIIa pathway is main initiator
-Result—conversion of soluble fibrinogen to insoluble fibrin—net of organized protein around platelet plug
-Result of coagulation phase is clot proper (thrombus)
iv. Clot dissolution (Fibrinolysis)
-Wound healing and restoration of blood flow
-Dissolution of clot by proteolytic actions of plasmin bound to clot process of fibrinolysis
2 goals of normal hemostasis
§ Prevent prolonged hemorrhage
§ Prevent spontaneous thrombosis
prothrombogenic factors (4)
Platelet Activators
Procoagulants
Vasoconstriction
Fibrinolytic Inhibitors
antithrombogenic factors (4)
Platelet Inhibitors
Anticoagulants
Vasodilators
Fibrinolytic Activators
causes of excessive bleeding (3)
Platelet deficiency
-Thrombocytopenias (quantitative consumption)
-von Willebrand’s (qualitative disorder)
Clotting factor deficiency
-Single factor eg. hemophilia (VIII, IX)
-Multiple factors ie. vitamin K deficiency
Fibrinolytic hyperactivity
mechanism of action of Vitamin K for hemorrhagic diseases
Confers biological activity: factors II, VII, IX, X; post-translational modification
forms of vitamin K
-Vitamin K1: phytonadione (foods)
-Vitamin K2: menaquinone (intestinal bacteria)
uses of vitamin K
Vitamin K deficiency
-Rodenticide toxicity
-Dicumoral toxicity (sweet clover poisoning)
Warfarin overdosing
oral vs parenternal route of vitamin K administration
- Intravenous route—best to avoid; anaphylaxis possible
- IM route- hematoma possible; SC recommended route
what does vitamin K require for intestinal absorption
bile salts
desmopressin acetate (DDAVP); uses, how it works, forms
- Transiently increases von Willebrand activity in mild von Willebrand disease
- Used prophylactically to control capillary bleeding during surgery
(Effects are short lived (2 hrs); repeat dosing—reduced effect) - Available as injectable or nasal spray (can be given SC)
what is protamine sulfate used for and how does it work
to treat heparin overdoses
-binds to heparin neutralizing its anticoagulant effects
-More effective against large molecular weight heparin molecules in unfractionated heparins versus the low molecular weight heparins
two things to consider and why for administering protamine sulfate
- Give IV slowly to avoid adverse reactions that can include collapse
- Accurate dosing needed; high doses can produce anticoagulant
effects
how do fibrinolytic inhibitors work
- Plasmin lyses fibrin and fibrinogen
Attaches to fibrin via lysine binding sites
what is aminocaproic acid (amicar) used for and how does it work
-Synthetic agent similar to lysine; blocks lysine binding site
-Competitively inhibits plasmin action on fibrin
-Incomplete lysis can lead to thrombi formation
Uses
* Bleeding from fibrinolytic therapy
* Adjunct therapy-hemophiliacs
three drug classes for thromboembolic disease
Systemic anticoagulants
Antithrombotic drugs
Fibrinolytic drugs
venous vs arterial thrombus
-Red thrombus-fibrin rich, large # RBCs; venous
-White thrombus-platelet rich; arterial
three prothrombic factors
-Local vessel injury
-Abnormal blood flow (stasis or turbulence)
-Altered blood coagulability (Hyperactivity of hemostatic mechanisms, Hypoactivity of fibrinolytic mechanisms)
ideal systemic anticoagulant… (2)
-Prevent pathologic thrombosis
-Allow normal response to vascular injury and limit bleeding
mechanism of action of heparin (unfractionated)
-Enhances (accelerates 100-fold) the action of Antithrombin III (AT-III)—forms heparin-ATIII complex
-AT- III inhibits activated clotting
factors especially thrombin (IIa) and
Xa—acts as a “suicide substrate”
uses of heparin
Primarily used in the initial treatment of thrombosis and thromboembolic disease
-Rapid onset of action renders it useful as an “acute anticoagulant”
(Oral anticoagulant usually given concurrently)
-Prevents new thrombus formation only !! (Does not lyse existing thrombus)
adverse effects of heparin
-Bleeding tendencies
-Monitor aPTT; 1.8-2.5X normal mean aPTT
-Protamine sulfate can neutralize heparin in overdose
advantages of low molecular weight heparins (enoxaparin) compared to unfractionated heparin
-Less bleeding tendencies possible
-Protamine sulfate is less active against LMW heparins
-Less risk of thrombocytopenia
-Improved pharmacokinetics– can give subcutaneous
adverse effects of warfarin
-Bleeding tendencies; can combat with Vitamin K1
-Serious bleeding requires fresh blood/plasma
-Warfarin crosses the placenta; don’t use in pregnancy; Heparin does not cross the placenta
