Anticoagulants

· Increase in serotonin which causes vasoconstriction.

· release of ADP and thromboxaneA2 from "activated platelets"

· formation of plug or thrombus

• ·pathway is a series of sequential reactions that convert inactive coagulation factors synthesized in the liver to active ones
• ·monitored by aPTT, activated partial thromboplastin time

·monitored by PT, prothrombin time, or International Normalized Ratio, INR (most often used)

• 1. Injectable anticoagulants: heparin and low molecular weight heparins (LMW)
• 2. Oral anticoagulants: warfarin
• 3. Thrombolytic (clot dissolving): streptokinase and tPA (dissolve clot for fibrin)
• 4. Antiplatelet (antiplatelet aggregation): acetylsalicylic acid, clopidogrel, abciximab
• Prevent fibrin formation

a. Pharmacodynamics, mechanism of action—a large negatively charged molecule that combines with the endogenous antithrombin III. This complex then promotes the destruction of factors such as Xa and thrombin

b. Pharmacokinetics - intermittent IV, continuous IV, SC (deep fat), not IM or oral. (does not cross the placenta)

• c. Types of treatment.
• (1) prevention of venous thrombosis
• (2) atrial fibrillation
• (3) phlebitis
• (4) cardiac or vascular surgery

• d. Toxicity, side effects
• (1) Hemorrhage - treatment - protamine (small positively charged molecule) (neutralizes heparin)
• (2) Osteoporosis (long term use)
• (3) Alopecia (long term use)
• (4) Thrombocytopenia (lack of platelets) (HIT: heparin induced thrombocytopenia watch for decreased platelets)
• (5) Allergic reactions

• (smaller particles of heparin)--LMW heparin—binds only to Xa not thrombin. Self administration (subcutaneously), less incidence of thrombocytopenia and does not require daily monitoring.
• --longer half life than heparin--> allows for home therapy

a. Pharmacodynamics, mechanism of action - competitive inhibitor of vitamin K-dependent synthesis of inactive clotting factors II, VII, IX, X.

b. Pharmacokinetics—becomes active only after active clotting factors have been degraded. (4-5 days)

• a) well absorbed by oral route
• b) 99% bound to plasma albumin
• c) metabolized in liver

c. Side effects - toxicity

• (1) hemorrhage
• (2) deformities in the fetus
• (3) tissue necrosis

d. Drug interactions

• - Synergists (potentiate effects)
• (1) acetylsalicylic acid (aspirin)
• (2) antibiotics (broad spectrum)
• (3) Vitamin E
• - Antagonists
• (1) barbiturates
• (2) vitamin K (especially food-tomatoes, dark leafy vegetables, bananas, fish)
• (3) estrogens

f. Treatment of toxicity - phytonadione (vitamin K1), plasma transfusion

• (Dissolve Clots)
• Plasminogen is converted to plasmin by t-PA (tissue plasminogen activator) on the site of the clot. Freely circulating plasminogen can also be converted to plasmin, but in this freely circulating form, plasmin is a relatively nonspecific serine protease (or enzyme that breaks down protein) and thus will also break down other clotting factors such as fibrin, fibrinogen, V, VIII, and XII in a nonspecific fashion (not clot specific).

• Mechanism of Action:
• Forms a complex with circulating plasminogen and catalyzes the conversion of plasminogen to plasmin which digests circulating fibrinogen and fibrin in thrombi (lacks fibrin, or clot specificity)
• Source:
• Strept. culture
• Adverse Reaction:
• Allergic and Bleeding
• Half-Life: 12-18 min

• Mechanism of Action:
• Forms a complex with fibrin bound plasminogen and catalyzes the conversion of plasminogen to plasmin directly on the clot.(Is fibrin or clot specific)
• Source:
• human tissue-type plasminogen activator
• Adverse Reaction:
• Bleeding
• Half-life:
• 2-6 min

acute myocardial infarction (within 3 hours), acute venous thrombosis, pulmonary embolism, cerebral embolism (within 3 hours-ischemic stroke)

b. clopidogrel (older drug with more side effects)

c. abciximab

• inhibition of platelet aggregation: mechanism of action
• Irreversible inhibition of cyclooxygenase (COX-1) and thus inhibiting the synthesis of
• thromboxane A2 in platelets.
• Effective for about a week until new platelets are synthesized.

• inhibition of platelet aggregation
• mechanism of action – blocks ADP receptors (receptors which stimulate platelet
• aggregation in the presence of ADP). Takes several days for peak action.

• inhibition of platelet aggregation
• Mechanism of action—An antibody which binds to platelets at the fibrinogen receptors
• (glycoprotein IIb/IIIa receptors ,and thus prevents binding of fibrinogen which in turn prevents platelet aggregation.