Anti-Coagulants, Anti-Platelets, Fibrinolytics Anti-Coagulants Parenteral (Rapid acting) Oral (Delayed acting) Standard Heparin Warf arin Low

Molecular Weight Heparin Fondaparinux (Pentasaccharide) Inhibits Function of Clotting Factors Inhibit Synthesis of Clotting Factors Help prevent thrombus formation No direct effect on a thrombus already formed
Standard Hepar in (Unfractionated Hepar in, Conventi onal Hepar in) Available in Mast Ce lls of Human T issue s Commercially from Porcine Intestinal Mucosa, Bovi ne Lung MOA Inhibit C lotting Factor Protease XIIa, XIa, IXa, IIa, Xa (12,11,9,2,10) (through action o n An tithromb in III) Binds to AT III, cause conformational change (for more rapid interaction wit h protea ses) AT III Inhibits C lotting Factor Proteases by forming complexes wit h them Pharmacokinetics Not absorbed from GIT (large molecule) (therefore given Parenta lly) IV IM SC Immediate onset Avoided Bioavailabi lity varie s action (Cause Hematoma) (onset action de layed 1-2 ho urs) Cleared from circulat ion by RES, Metaboli sed by Liver Half Life - (1-1 hour s)(effect disappears with in h ours) Do not cross Placenta (big molecule) (can be g iven in Pregnancy) Does not enter Breast Mi lk Clin ical App licatio n (Venous Thromb os is) Therapy Prophylaxis DVT, Pulmonary Emboli sm, Arteria l Thromb us & R isk (Immobilized, Surgical pt) Embolism, MI DVT No direct effect on Thromb us that has been Pulmonary Embol ism formed Does not guarantee Thrombos is does not occur Prevent Further Extensi on, Emboli sation of Formed Clot ( Ri sk 60-80%) Dose tha n Prop hylaxis Subcutaneous Adm inist ration Monito r Anticoagu lant Activity aPTT Adverse Effects Bleeding (ep istaxis, hematur ia, melena, ecchymosis) Heparin Induced Thrombocytopenia (HIT) Excess Anticoagulant Managed by Dose/ Discontin ue Heparin Antidote Protami ne Sulfate Heparin Induced Thrombocytope nia Low Mo lecular Weight Heparin (LMWH) (Enoxaparin, Daltepari n, Nadroparin) Fragments 1/3 of UFH size All Porcine ba sed MOA Inhibit Protea se Xa (via Anti-th rombin) Pharmacokinetics Smaller molecular size (compared to standard he parin) Better subcutaneou s b ioavailabi lity (compared to standard heparin) Half-Life - (les s frequent dos ing requ ired) Cleared Rena lly (Half-life in Re nal Fai lure require dose reduction) Clin ical App licatio n Therapy Prophylaxis Adverse Effects Bleeding (e specially if overdo se) Heparin ind uced thrombocytopenia ( i ncidence compared to standard he parin) Warfarin Vitamin K Antagon ist MOA Inhibit synthe si s of active Vitamin K depende nt clotti ng factors by liver (Factor VII, IX, X, II) Vitamin K Cofactor i n gamma carboxylation (needed fo r activation) of these factors duri ng synthes is (these factors ineffective i n coagulation) Pharmacokinetics Good GIT Absor ption (100% B ioavailab ility) Half-Life - ( >36 h ours) (da ily do sing is adequate) Transformed to Inactive Metabol ite by Liver Liver Disease (enhance anticoagulant effect, start d ose in liver fai lure) Duration of Action after drug d iscontinue d pe rsi st to 4-5 days Clin ical App licatio n Long term anticoagulant (eg. after Venou s Thr ombosi s) No effect on clotting factors already i n circulatio n Full Therapeut ic Effect Delayed 4-5 days (time balance between degradation of exist ing clotti ng factors, inh ibited synthes is of new factors) Monito r Anticoagu lant Effects Prothrombin Time International Normal ised Ratio (INR) (INR = Patient PT / Contr ol PT) Adverse Effects Bleeding (re lated to inten sity of a nticoagulation)( Antidote Vitamin K) Necrosis, Gangrene of Skin, Soft Ti ssue s Teratogenic (passes Placenta)(should not use in pregnancy) Drug Interactions Diet ( i n Vitamin K content - Warfar in effect), Compliance, Drugs, Herbs, Alcoho l Pharmacokinetic Pharmacodynamic Enzyme induction, En zyme Inhibit ion, Synergism Hepatic Disease Plasma Protein Bi nding Drugs Aspir in Drugs Inhib iting Enzyme Inducers Metabolism Plasma conc. Plasma conc. Decrease Effects Enhance Effect Fondaparin ux Synthetic Pentasaccharide MOA Selective Inhibitor of Activated Factor X Works by b indi ng to AT III, Potentiates Neutral isation of Factor Xa Interupts Bl ood C oagulation cascade, Inhibit Thromb in, Thrombus development Pharmacokinetics Excreted in Urine Half-Life - (17-21 hour s) (pro longed in Rena l Impairment) Clin ical Ind ication Similar to LMWH, Heparin

jslum.com | Medicine

Anti-Platelets Cyclo-oxygenase ADP Receptor Inhibitors Inhibitors Aspirin Clopidogrel Inhibit Platelet Aggreg ation
Clin ical App licatio n Prevent 2 CVS events w ith h istory of vascular events (eg. Post MI, Stroke) Better at preventi ng Arter ial Th rombos is (not effective in preventi ng venous thrombo sis) Thromboxane A2, ADP sign ificant plate let aggregators Antiplate lets COX Inhibito rs Inhibit p latelet Thromboxane A2 production Aspir in

Fibrinolytics/ Thrombolytics Strep tokinase (widely used) Urokinase Tissue Plasminogen Activator (tPA) Increase Fibrinolysis
Fibrino lytic System Dissolves Intravascular Clot (due to action of Pla smin, an en zyme that dige st Fibr in) Plasminogen (inactive Precursor) Plasmin Enzyme that Digest Fi brin Clot s Fibrino lytics Promote Plasm in Formation (from Pla sminogen) Clin ical App licatio n Pulmonary Embol ism Myocardial Infarction (MI) (best w ithin 6 ho urs)(ASAP) All given Intravenous ly Contrain dicatio n Recent Surgery Bleeding Streptokina se Protein pr oduced by haemolytic st reptococci Adverse Effects Bleeding Allerg ic reactions (ant igenic) Anaphylaxis (rare ly) Fever (rarely) Tissue Pla smin ogen Activator Endogenously released from Endothe lial cells

ADP Inhibito rs Inhibit ADP-induced Platelet aggregation Ticlopidi ne Clopid ogrel

Cyclooxygenase Inhibito rs (eg. as pir in) (Ora lly)

In Platelet, major COX pro duct is TxA2 (induce platelet aggregation) Aspirin Inhibit Cyclooxygenase en zyme Irreversibly Inhibit synthe si s of Thr omboxane A2 Bleeding T ime Pr olonged Given Orally Daily ADP-Inhibitors (eg. Clo pid ogrel, Ticlopid ine) (Orally) Aspirin Alterna tive Unable to To lerate Aspir in (GI Intolerance, Hypersensitivity) Use with Aspir in (synergi sm) MOA Inhibit ADP Induced Platelet Aggregation Adverse Effects BM Suppres sion (eg. Neutropenia, Thrombocytopenia) GI Disturbances Haemorrhage

Differences - UFH, LMWH Structu re MOA UFH Larg e Molecular Weight Inhibit Proteases XIIa, XIa, IXa, IIa, Xa via Antithrombin aPTT Half-Life (about 1 hour) Do not cross placenta Not absorbed orally Protamine Sulfate LMWH Smaller Molecular Size Mainly Inhibit Protease Xa via Antithrombin aPTT not useful Half-Life (3-4 hours)( frequent dosing) Do not cross placenta Not absorbed orally No specific antidote SC Bioavailability better

Monitor Effects Kinetics

Antidote Kinetics

Differences Heparin, Warfarin Heparin Parenteral (IV, SC) Half-Life Monitoring by aPTT Rapid Anticoagulant effect Inhibit Proteases by action on Antithrombin III
Fetal Warfar in Syndr ome

Warfarin Oral Half-Life Monitoring by INR Delayed eff ects (days) Impair synthesis of Vitamin K dependent clotting factors

Infant wit h Hypoplastic nose Flat face Low nasal b ridge Altered Calcification