Pharmacology of Blood Antiplatelets & Anticoagulants Drugs PDF

Sin Weel Il stone ↑ doting Pharmacology of Blood (anti platelets, anticoagulants ,Thrombolytics and Drugs for Anaemia)...

Sin Weel Il stone ↑ doting Pharmacology of Blood (anti platelets, anticoagulants ,Thrombolytics and Drugs for Anaemia) ↓ makein Dr. Amani Alharbi PharmD, MSc, PhD PHT 379 0 Objectives Mechanisms of Hemostasis Platelets activation overview Antiplatelets drugs Anticoagulants, definition and mechanisms Thrombolytics, definition and mechanism Agents used for Anemaia 2/11/2025 1 Mechanisms of Hemostasis: Role of Platelets in Vascular Repair and Blood Clot Formation 1. Primary Hemostasis: First & Quick - Immediate - response to vascular injury. - Involves platelet adhesion, activation, and aggregation to form a temporary platelet plug. - Key mediators: von Willebrand factor (vWF), ADP, thromboxane A2 (TXA2). 2. Secondary Hemostasis: - Reinforces the platelet plug with a fibrin mesh. - Involves the coagulation cascade, leading to thrombin activation and fibrin clot formation. - Key factors: Coagulation factors (Intrinsic & Extrinsic pathways), thrombin, fibrinogen. 2/11/2025 2 When a blood vessel is damaged, platelets become activated Plattake to form a clot and prevent excessive bleeding. This process anti involves: 1. Adhesion - Endothelial injury exposes subendothelial matrix proteins like collagen and von Willebrand Factor (vWF) - Platelets bind to vWF via glycoprotein (GP) Ib/IX/V receptor, anchoring them to the injury site. 2. Activation - Bound platelets change shape and release granules containing ADP, thromboxane A2 (TXA2), serotonin, and other signaling molecules. - These signals activate additional platelets via P2Y12 (ADP receptor) and thromboxane receptors, amplifying the response. 3. Aggregation - Activated platelets express GPIIb/IIIa receptors , which bind fibrinogen, linking platelets together to form a stable - platelet plug. - This plug is reinforced by fibrin in secondary hemostasis, forming a stable clot. L 2/11/2025 3  thrombotain # Antiplatelets Drugs imp ax every made Antiplatelet drugs are medications that inhibit platelet aggregation and prevent the formation of blood clots (thrombi) in arteries. They work by interfering with platelet activation pathways, reducing the risk of clot-related conditions. Blood clotting is a complex process involving both circulating proteins and platelet activation. When blood vessels sustain damage, platelets bind to exposed collagen and von Willebrand factor, leading to further platelet activation and the formation of a plug. This plug is solidified by a fibrin meshwork. Central to this mechanism are platelet activators like adenosine diphosphate (ADP), serotonin, and thromboxane A2, with thromboxane A2 being synthesized mainly by the COX enzymes, especially COX-1. Antiplatelet drugs such as aspirin counter platelet aggregation by targeting COX enzymes and P2Y12 ADP receptors. ↑CoN1 inhikefor Others, like abciximab, eptifibatide, and tirofiban, inhibit GP IIb/IIIa receptors, preventing the binding of fibrinogen to platelets. Additionally, phosphodiesterase inhibitors like dipyridamole and cilostazol increase cAMP and disrupt platelet function, resulting in arterial dilation. 2/11/2025 4 Drug Class Examples Mechanism of Action Effects Indications Side Effects the enzyme most impo breakdown Irreversibly Inhibits COX-1 enzyme, Aspirin inhibit thromboxane A2 production Reduces platelet - Prevention of Gastrointestinal Aspirin (COX Inhibitor) (Acetylsalicylic The inhibitory effect is rapid, and aspirin-induced aggregation, prevents cardiovascular events irritation, bleeding, suppression of thrombox- ane A2 and the resulting Acid) suppression of platelet aggregation last for the life of clot formation (e.g., MI, stroke) - ulceration - the platelet, which is approximately 7 to 10 days. Clopidogrel, Ticagrelor Irreversibly binds to the P2Y12 Reduces platelet Acute coronary syndrome Bleeding, gastrointestinal P2Y12 Inhibitors (reversible), receptor on platelets, preventing activation and (ACS), post-angioplasty, disturbance Prasugrel ADP-induced platelet aggregation aggregation stroke prevention Aspirin, clopidogrel are some of the most common oral medications M Phener Inhibit GPIIb/IIIa receptor, Bleeding, Glycoprotein IIb/IIIa Abciximab, Eptifibatide, Prevents final step in Acute coronary syndrome preventing fibrinogen thrombocytopenia, Inhibitors Tirofiban platelet aggregation (ACS), PCI binding hypotension Abciximab, and tirofiban are the most frequently used intravenous medications. Hospital Inhibits phosphodiesterase, increasing cAMP levels in Inhibits platelet Phosphodiesterase platelets thereby resulting in Prevention of stroke, TIA, Headache, dizziness, Dipyridamole aggregation, Inhibitors decreased thromboxane A2 used with aspirin gastrointestinal issues vasodilation synthesis. 2/11/2025 Reduces platelet 5 Increases cAMP levels, Peripheral artery disease aggregation, Headache, palpitations, Other Agents Cilostazol inhibiting platelet (intermittent  wank Anticoauglants facter back X stronges anti c oag the siff whe gable Definition: work L P Ei activable Anticoagulants are drugs that inhibit the coagulation cascade to prevent the formation and growth of blood clots. Unlike antiplatelets, which 9 stand must prevent platelet aggregation, anticoagulants act on clotting factors ↳ 10 & in the blood to reduce fibrin formation. g: mosts enhausmet and: thomping activator Blooding K factor 1 D ⑱97-2 2/11/2025 6 Class Examples Mechanism of Action Route # unticongulant mad Inhibits vitamin K- Oral, Note: The International - Test Normalized Ratio (INR) is the standard by which the anticoagulant activity of warfarin Vitamin K Antagonists therapy is monitored. Warfarin has a Warfarin dependent clotting factors - narrow therapeutic index. Therefore, it is (VKAs) important that the INR is maintained within (II, VII, IX, X) - the optimal range as much as possible, and - frequent monitoring may be required. & Enhances antithrombin III, Unfractionated Heparin insideapoly Heparin inhibiting thrombin (Factor IV/Subcutaneous (UFH) - IIa) and Factor Xa inveronfere Low Molecular Weight Inhibits Factor Xa more Enoxaparin, Dalteparin Subcutaneous Heparins (LMWHs) selectively than UFH Direct Thrombin Inhibitors Directly inhibits thrombin Oral (Dabigatran), IV Dabigatran, Bivalirudin (DTIs) (Factor IIa) (Bivalirudin) 2/11/2025 Rivaroxaban, Apixaban, 7 Factor Xa Inhibitors Directly inhibits Factor Xa Oral Edoxaban  not breakdown coagulatio only stopping it the Feature Unfractionated Heparin (UFH) not brocated sorm Fractionated Heparin (LMWH) & Molecular Weight Large, variable size (5,000–30,000 Da) Smaller, more uniform size (4,000–6,500 Da) Inhibits both Factor IIa (thrombin) and Factor Mechanism of Action Preferentially inhibits Factor Xa more than Factor IIa Xaequally by enhancing antithrombin III Bioavailability Lower (highly variable due to plasma protein binding) Higher (~90%) with predictable effects Half-life Short (~1.5 hours) Longer (~4–6 hours) Monitoring Requires aPTT monitoring No routine monitoring needed Administration IV or subcutaneous Subcutaneous Reversal Agent al licot Protamine sulfate (fully effective) Protamine sulfate (partially effective) Prophylaxis & treatment (e.g., DVT, PE, post-surgery Clinical Use Acute treatment (e.g., DVT, PE, MI, perioperative use) prevention) Renal excretion (dose adjustment needed in renal Renal Clearance Minimal (preferred in renal impairment) dysfunction) 2/11/2025 8  deras a cognat birch activation Thrombolytics mee Acute thromboembolic disease in selected patients may be treated by the administration of drugs that activate the conversion of plasminogen to plasmin, a serine protease that hydrolyzes fibrin and, thus, dissolves clots. Used to actively break up any newly formed clot, Activation of plasminogen by thrombolytic drugs. such as those found in patients with acute myocardial infarction, acute stroke secondary to cortex with blood clot, or lower leg ischemia. I Alteplase, Streptokinase, Tenecteplase are the most frequently used medications in this class. Patients on these medications are at increased risk of bleeding, IV line to be used with caution and with permission from physician. 2/11/2025 9  Drugs for Anemia Anemia is characterized by low plasma hemoglobin levels due to a reduced number of red blood cells or low hemoglobin content in the blood. Common symptoms include fatigue, palpitations, shortness of breath, pallor, dizziness, and insomnia. Anemia can result from various causes, including chronic blood loss, bone marrow disorders, hemolysis, infections, malignancy, endocrine deficiencies, and renal failure. cancer e Drug-induced anemia occurs due to toxic effects on blood cells, hemoglobin production, or imerythropoietic organs. a de Nutritional anemias arise from deficiencies in iron, folic acid, or vitamin B12, essential for mustmer normal red blood cell production. Additionally, individuals with genetic conditions like sickle cell disease may benefit from treatments like hydroxyurea. While severe anemia may require blood transfusions, mild-to-moderate anemiais treated using agents like iron, folic acid, vitamin B12, and erythropoiesis-stimulating agents. 2/11/2025 10 Agents used to treat anemias 1. Iron Supplements Mechanism: Replaces iron stores necessary for hemoglobin synthesis. Common Drugs: Ferrous sulfate (oral), Iron dextran (IV/IM) and Ferrous gluconate (oral) Indications: Iron-deficiency anemia. Side Effects: GI upset (nausea, constipation), black stools, potential toxicity (especially in children). 2. Vitamin B12 (Cobalamin) Mechanism: Essential for DNA synthesis and maturation of red blood cells. Common Drugs: Cyanocobalamin (oral, IM) and Hydroxocobalamin (IM) Indications: Pernicious anemia, vitamin B12 deficiency. Side Effects: Allergic reactions (rare), injection site reactions. 2/11/2025 11  Agents used to treat anemias 3. Folic Acid Mechanism: Necessary for DNA synthesis and red blood cell production. Common Drugs: Folic acid (oral) , Folinic acid (leucovorin, injectable) Indications: Folate deficiency anemia, megaloblastic anemia. Side Effects: Well-tolerated, but high doses may mask B12 deficiency duener4. Erythropoiesis-Stimulating Agents (ESAs) patient Mechanism: Stimulates red blood cell production in the bone marrow. Common Drugs: Epoetin alfa (Epogen) – subcutaneous/IV Darbepoetin alfa (Aranesp) – subcutaneous/IV Indications: Anemia due to chronic kidney disease, chemotherapy, HIV treatment. Side Effects: Hypertension, increased risk of thrombosis, headache, fatigue. 2/11/2025 12 Agents used to treat anemias 5. Hydroxyurea Mechanism: Reduces the frequency of sickle cell crises by increasing fetal hemoglobin levels. Common Drugs: Hydroxyurea (oral) Indications: Sickle cell anemia. Side Effects: Bone marrow suppression, gastrointestinal upset, teratogenic effects. 6. Iron Chelators (for Iron Overload) Mechanism: Binds excess iron to prevent toxicity in conditions like thalassemia. Common Drugs: Deferoxamine (Desferal) – IV and Deferasirox (Exjade) – oral Indications: Chronic iron overload due to blood transfusions. Side Effects: Liver toxicity, gastrointestinal issues, vision/hearing problems. 2/11/2025 13