1. Prothrombotics
1.1. Vitamin K
1.1.1. Vitamin K1 (Phytonadione) - acquired from green leafy vegetables (Broccoli, Cauliflower, brussel sprouts); Medically important
1.1.2. Vitamin K2 (Menaquinone) - part of normal flora
1.1.3. Vitamin K3 (Menadione) - not clinically important
1.1.4. Uses of Vitamin K: - Management of bleeding associated with vitamin K deficiency and - Warfarin overdose - Prophylaxis against hemorrhagic disease of the newborn
1.2. E-aminocaproic acid
1.2.1. • MOA: Inhibits activation of plasminogen • Analog of Tranexamic Acid
1.3. Aprotinib
1.3.1. MOA: Inhbiits plasmin
1.3.2. Use: given during CABG (Coronary Artery Bypass-pass Graft) in patients with risk of bleeding
2. Anti-thrombotics
2.1. Anticoagulants
2.1.1. Direct thrombin inhibitor
2.1.1.1. Parenteral
2.1.1.1.1. Hirudin (Natural) and Lepirudin (Recombinant/Clinically useful)
2.1.1.1.2. Others
2.1.1.2. Oral
2.1.1.2.1. Dabigatran - Oral anti-factor IIa or Oral direct thrombin inhibitor
2.1.2. Indirect thrombin inhibitor
2.1.2.1. Parenteral
2.1.2.1.1. Heparin
2.1.2.1.2. Uses (UFH and LMWH)
2.1.2.1.3. Antidote for Heparin poisoning: Protamine sulfate
2.1.2.2. Oral
2.1.2.2.1. Apixaban and Rivaroxaban (NEWER)
2.1.2.2.2. OLDER - Obsolete: • Dicumarol - 1st oral anticoagulant and rodenticide • Phenprocoumon - very long half-life
2.1.2.3. Warfarin
2.1.2.3.1. MOA: Inhibits VKORC1 enzyme (Vit.K Epoxide Reductase Complex)s
2.1.2.3.2. • Onset of effects: Delayed • blocks clotting factors 2,7,9,10 • Monitored by prothrombin time (PT) and International normalized ratio (INR)
2.1.2.3.3. Warfarin is a procoagulant for the first 3-5 days of therapy (Heparin is given instead)
2.1.2.3.4. Uses: Warfarin • When chronic anti-coagulation is necessary except during pregnancy • Prosthetic heart valves • VTE prophylaxis • Stroke prophylaxis in AF
2.1.2.3.5. Monitoring of effect - Parameter: Prothrombin time - INR
2.1.2.3.6. Dose: - Caucasians: 5-10 mg/dL - Asians: 1-2.5 mg/dL
2.1.2.3.7. Adverse effects
2.1.2.3.8. Adverse effects PT2 1. Cutaneous necrosis within 1st week of therapy 2. “Purple Toe Syndrome” - Cholesterol embolization; seen after 3 weeks of therapy 3. CI: Pregnancy (1st tri: Teratogenic; 3rd Tri: Hemorrhagic disorder in newborn)
2.2. Antiplatelets
2.2.1. Thromboxane Synthesis Inhibitor
2.2.1.1. Aspirin at doses </= 325mg/day
2.2.1.2. Uses: DOC Acute Coronary Syndrome and Stroke Prevention/Prophylaxis
2.2.2. Irreversible ADP Inhibitor (Thienopyridines)
2.2.2.1. Ticlopidine
2.2.2.1.1. Dose: 250 mg BID PO
2.2.2.1.2. Uses: Same as ASA (Alternative to ASA)
2.2.2.1.3. AE: Agranulocytosis; Neutropenia (Low Neutrophils) ; Thrombocytopenia (Low platelets) • Requires weekly WBC-platelet count monitoring at least for the 3 months of therapy
2.2.2.2. Clopidogrel
2.2.2.2.1. Dose: 75mg OD
2.2.2.2.2. MOA: Clopidogrel is a prodrug (Converted into an active form by CYP2C19)
2.2.2.2.3. Implication: Inhibited by proton pump inhibitors (except Pantoprazole)
2.2.2.2.4. Use: Same as ASA (Less effective for preventing stroke)
2.2.2.3. Prasugrel
2.2.2.3.1. MOA: Reversible ADP inhibitor (Non-Thienopyridine)
2.2.2.3.2. Use: has similar indications, but works faster and is preferred in patients with diabetes.
2.2.3. Phosphodiesterase Inhibitors
2.2.3.1. CAMP IS ANTI-AGGREGANT
2.2.3.2. Dipyridamole
2.2.3.2.1. MOA: Inhibits adenosine uptake
2.2.3.2.2. Uses: antiplatelet aggregation, Combined with ASA or Ticlopidine
2.2.3.2.3. Side Effect: Coronary Steal Phenomenon
2.2.3.3. Cilostazol (Pletaal)
2.2.3.3.1. MOA: Inhibits Adenosine Uptake
2.2.3.3.2. MOA: Vasodilator in the management of intermittent claudication (limpness, weakness)
2.2.3.3.3. Uses: Anti-platelet aggregation, Combined with ASA or Ticlopidine
2.2.4. Glycoprotein IIb/IIIa Inhibitor
2.2.4.1. MOA: Inhibits glycoprotein receptors
2.2.4.2. Example: Abciximab, Tirofiban, Eptifibatide
2.2.4.2.1. Use: Presentation of Thrombosis after angioplasty
2.2.4.2.2. Route: All are given IV
2.3. Fibrinolytics
2.3.1. MOA: Promotes conversion of Plasminogen —> Plasmin (Active Serine Protease)
2.3.2. Plasmin - destroys Fibrinogen which eventually becomes a Fibrin clot (not effective with red thrombus)
2.3.3. Uses 1. Management of Acute Pulmonary Edema 2. Management of Central Deep vein Thrombosis 3. Management of Acute Ischemic Stroke 4. Management of STEMI (Heart Attack)
2.3.4. Contraindication: 1.Presence of Active Bleeding 2.Visceral Cancer (GIT) 3.Peptic Ulcer Disease 4.Pregnancy (Give UFH) 5.Recent Surgery 6.Hemorrhagic stroke
2.3.5. Examples: 1.) Streptokinase 2.) Recombinant t-PA (Tissue Plasminogen Activator) 3.) Urokinase
2.3.5.1. Streptokinase
2.3.5.1.1. • Not an enzyme, but a protein derived from B-hemolytic streptococci • Derivative: APSA (Amsolyted Plasminogen Streptokinase Activator Complex) • Source: B-hemolytic streptococci
2.3.5.1.2. Adverse Effects: Allergic Reactions (Remedy: Pre-medication with Diphenhydramine IV)
2.3.5.2. Recombinant t-PA
2.3.5.2.1. Ex: Alteplase, Reteplase, Tenecteplase
2.3.5.2.2. Advantage: Minimal risk of bleeding and can be given multiple times for Acute MI
2.3.5.2.3. Disadvantage: Higher incidence of bleeding because it is require to be used with Heparin
2.3.5.3. Urokinase
2.3.5.3.1. Derived from kidneys (Renal cells)