Mechanism: provides scaffold for AT3 binding which inactivates IIa/thrombin and Xa

Treatment: Acute MI, DVT, rapid acting Anticoagulant

Side-effects: Need to monitor aPTT or else risk of HIT, spontaneous hemorrhage, allergies, alopecia, osteoporosis, long-term use reduces mineral corticoid efficiency. Protamine sulfate (anticoagulant) given for overdose.

Doesn't cross placenta and IV administered (unlike Warfarin). IV administration for patients with active thrombosis or pulmonary embolism

LMWH

Enoxaparin, Dalteparin, Tinzaparin

Mechanism: allosteric binding to AT3, inactivates serine proteases IX, X, XI, XII

Treatment: rapid acting anticoagulant less able to inhibit platelet aggregation

Side-Effects: allergies, alopecia, osteoporosis, long-term use reduces mineral corticoid efficiency, protamine sulfate (anticoagulant) given for overdose

Does not need to be monitored, Longer HL than HMWH, Less likely to cause HIT. Given SubQ for patients requiring low dose prophylaxis. Does not cross placenta or accumulate in milk of mothers

Mechanism: synthetic analog of the pentasaccharide binding sequence of heparin; does not bind PF4 (does not cause HIT); cleared by kidneys (contraindicated for elevated creatine clearance)

Treatment:  subQ

Mechanism: most potent direct inhibitor of thrombin given parenterally and is monitored by PTT. It is bivalent, binds both catalytic site and exosite of thrombin. Has little effect on platelets

Treatment: anticoagulant given to patients with thrombocytopenia 

Side-effects: Long term infusions leads to development of antibody against thrombin-lepirudin complex causing enhanced bleeding

Mechanism: bivalent with short half life. clearance is 20% renal rest is metabolic. inhibits platelet aggregation

Treatment: coronary angioplasty

Mechanism: synthetic derivative of arginine that directly inhibits thrombin. Monovalent action of catalytic site of soluble and clot bound thrombin. IV infusion. Eliminated by the liver and eliminated in the bile 

Treatment: anticoagulant for HIT and prophylaxis

 Side Effects: Hemorrhage (2%) and allergic reactions (10%)

Mechanism: inhibits gamma-carboxylation of glutamic acid in II, VII, IX, X, C, and S (Vitamin K antagonist). Prevents recycling of Vitamin KO to K. Slow onset of action. HL of 36hr. Oral, rectal, IV administration.

Treatment: Racemic mixture; typically given after heparin

Side-effects: Hemorrhage. It is teratogenic and cause fetal bone defects as well as other problems. It can induce an early transient hypercoaguable state since Protein C is needed for anticoagulation-cutaneous necrosis in first week of therapy or even venous thrombosis

 Resistance: Excess VitK intake (or antidote), hereditary resistance

Sensitivity: defect in cytochrome P450 allele, hepatic disease, dec VitK, CHF

Antidotes: VitK/phytonadione, Konyne 80, Proplex T (with large amounts of prothrombin)

Mechanism: sufficient dose must be administered to overcome antibodies targeted against Streptokinase. Activates plasmin. HL is 23min. IV admin.

Treatment: Effective against young thrombi, pulmonary embolism, acute MI

Side-effects: Bleeding, antigenic (allergic), generalized depletion of fibrinogen

Mechanism: Fibrinolytic, converts plasminogen to plasmin. synthesized by kidney, half life is 15min

Treatment: not antigenic (derived from human)

t-PA

Alteplase, Reteplase, Tenecteplase

Mechanism: selectively activates plasminogen bound to clots. HL 3min in plasma.

Alteplase-recombinant

Reteplase-deleted amino acids

Tenecteplase-mutant form with longer life and specificity

Treatment: not antigenic and useful in patients with antibodies to streptokinase

Mechanism: Inhibition of COX by irreversible acetylation; Platelets have no nucleus and thus effect lasts the lifetime of platelets (7-10 days). Endothelial cells are site of PGI2 production and can regenerate COX.

Treatment: Give low dose to selectively inhibit platelet COX (EC requires high dose), prophylaxis of MI

Side-effects: Inc. risk of bleeding and greater incidence of hemorrhagic stroke, peptic ulcer and GI bleeding

Mechanism: irreversibly binds to ADP-receptor on platelets

Treatment: anticoagulant

Side-effects: Rash, diarrhea, abdominal pain, intracranial and GI hemorrhage; Ticlopidine causes severe neutropenia

Mechanism: monoclonal antibody against GPIIb/IIIa complex. Given parenterally.

Treatment: coronary angioplasty and acute coronary syndrome

Mechanisms: Eptifibatide is an analog of fibrinogen's binding to its receptor. Tirofiban is an analog of RGD which is the recognition sequence of GPIIb/IIIa receptor. Both given parenterally.

Mechanism: vasodilator that inhibits platelet function by inhibiting adenosine uptake and cyclic GMP phosphodiesterase. Used with aspirin

Treatment: Reduce risk of vascular death, stroke, or MI after a transient ischemic attack or minor stroke

Mechanism: blocks cAMP phosphodiesterase inhibiting platelet aggregation

Treatment: claudication associated with peripheral vascular disease

Vitamin K

Source?

Absorption?

Treatment?

Source: leafy green vegetables (K1, phytonadione), but bacteria in intestines also produces it (K2, menaquinone)

Absorption: requires bile salts and absored in intestines

Treatment: depression of prothrombin time by excess warfarin or VitK def, IV admin should be slow or else can cause dyspnea, chest and back pain

Mechanism: Synthetic inhibitor of fibrinolysis. Binds plasmin and plasminogen, interferes with plasmin function

Treatment: therapy in hemophilia, antidote for fibrinolytic therapy, patients with postsurgical bleeding (GI and bladder)

Side-effects: Intravascular thrombosis, hypotension, myopathy, abdominal discomfort, diarrhea, and nasal stuffiness

Mechanism: Serine protease inhibitor, IX, X, XI, XII. Forms reversible stoichiometric enzyme inhibitor-complexes (ie plasmin-streptokinase complex). IV admin.

Treatment: Used to limit blood loss in high risk patients (renal failure, MI, heart failure, encephalopathy)