Pharm exam 1: section 3

Venous thromboembolism: prevention and tx Stroke prevention in setting of afib Ischemic stroke Prosthetic cardiac valve Coronary and PVD Hypercoagulable disease Prophylaxis for clotting events in high risk pt that might have high risk procedure

Vitamin K antagonist Inhibits synthesis of Vitamin K dependent clotting factors: X IX VII (half life = 6 hrs) II (prothrombin) (half like 60 hours) Coagulation inhibitor proteins C, Z, S Average half life 36-42 hrs (3-4 days) Onset: depends on time needed to deplete factors

Well absorbed PO Metabolized by enzymes CYP1A2 & CYP2CP Precautions and C/I • Pregnancy category X • Cautious use in pt w/ fall risk, dementia, or uncontrolled HTN • avoid: recent hemorrhagic stroke, active bleeding, recent trauma/surgery, presence of spinal catheter, aneurysm, CNS tumor

Bleeding -antidote is vitamin K Allergic reactions Drug interactions • simvastatin, fish oil, garlic, prednisone may increase INR • Phenytoin and phenobarbital may decrease INR • decreased by foods w/ vitamin K

Clinical Dosing Start @ 5mg/day (7.5mg/day if weight > 80 kg) Consider lower dose if: > 75 yo Multiple cormorbidities Elevated liver enzymes Changing thyroid status INR hows prolongation w/in 3 days after starting d/t rapid depletion of factor VII Full anticoagulation after depletion of factor II depleted (2-14 days) Check daily until in range on 2 consecutive days Check 2x weekly for 1-2 weeks Then less frequently (@ least every 6 weeks)

INR 2-3 VTE DVT stroke prevention in afib valves hypercoagulable condition INR 2.5- 3.5 Heart valvle hypercoagulable condition

Direct thrombin inhibitor Poor bioavailability formulated as prodrug Few drug interactions Renal clearance Half life: 14-17hrs Avoid in pt w/: CrCl <15 ml/min dialysis prosthetic heart valve Adverse reactions bleeding (administer fresh frozen plasma) GI vs intracranial bleeding GI effects Drug -drug interactions • quinidine: increase levels by 100% • amiodarone: increase levels by 50% • rifampin: may decrease effects • PPIs and antacids - separate doses by 2 hrs Dosing: reduce risk of CVA in pt w/ afib 150mg BID - normal renal function 75mg BID - decreased renal function Check hepatic function at baseline and periodically if concern Cannot crush Cannot be put in pill box bc its packaged in moisture proof container

Direct thrombin inhibitor Poor bioavailability formulated as prodrug Few drug interactions Renal clearance Half life: 14-17hrs Avoid in pts w/ heart valve Avoid in CrCl < 30ml/min must be taken with food to improve bioavailability

Direct thrombin inhibitor Poor bioavailability formulated as prodrug Few drug interactions Renal clearance Half life: 14-17hrs Least dependence on CrCl good for pts w/ kidney function issues

Less drug-drug interactions Cannot use in CrCl: >95ml/min -> cause stroke

DVT and PE treatment DVT prevention stroke Bind to factor Xa: Block thrombin faster onset than warfarin; injectable bridge therapy not necessary as with warfarin no dietary interactions dosing adjustment not necessary

From warfarin: start when INR at lower end of therapeutic range From unfractionated heparin: start when heparin is discontinued From low molecular weight heparin (LMWH): start when LMWH due next (usually 12 hrs from last dose)

Binds w/ antithrombin III inactivates factors IXa, Xa,XIIa, XIII Given: IV or subQ (immediate action - emergency situations) Not absorbed in GI Extensively protein bound Metabolized by liver / renal excretion Caution in Pregnancy; category C Avoid in advanced hepatic or renal disease Avoid in bleeding disorder or active bleeding

HIT (immune response to heparin) Life threatening bleeding Pain at injection site, bruising: subQ Antidote: protamine sulfate Drug interactions Cephalosporins and PCNs warfarin, antiplatelets, thrombolytics Valproic acid

Given 12 hrs pre-op Maintenance q 8-12 hrs for 7 days post op Monitor: aptt platelet and hematocrit q 2-3 days initially Indications acute thromboembolism VTE prophylaxis

Fragments of unfrationated heparin Inactivates thrombin and factor Xa No lab monitoring Fixed dosing at prophylaxis: aptt may not be significantly prolonged at prophylaxis doses Weight based with therapeutic dosing: At therapeutic doses aptt prolongation not used to measure therapeutic effect Half life: 108-252 minute

DVT or PE Pre-op given 12 hrs before surgey Still at risk for HIIT

DVT Hip fracture surgery or knee replacement Risk for HIIT is subsequently lower

Dosing may vary from day to Pills are different size and color for dose Must explicitly state each day pt takes a certain dose to avoid miscommunication Educate about INR checks Warn of bleeding complication Educate about food (leafy greens, asparagus, onion, garlic)

Subq administered at home Show how to administer Rotate sites Bleeding

Inhibits cyclooxyrgenase (COX) Interferes w/ platelet aggregation Well absorbed PO; take with food to be prevent GI distress) Metabolized in liver Renally excreted (pH affects excretion) Contraindications Hypersensitivity cross sensitivity w/ NSAIDS Pregnancy category C (D in 3rd trimester) Reye's syndrome in children Adverse reactions bleeding GI upset and bleeding salicylism (tinnitus) Interactions other anti platelet, anticoagulant, fibrinolytic Herbals (ginko, garlic, ginseng) NSAIDS Dosing MI prevention: 75-162mg daily afib: 75-325mg CVA or TIA: 50-100mg daily Education take with a full glass of water ASA must be stopped 7 days before surgery Adverse: ASA toxicity: tinnitus, dizziness cerebral edema seizure bleeding or bruising

Combination product (25mg ASA/ 200mg ER dipyridamole) Dipyridamole inhibits platelet adhesion but MOA unknown

Reduce platelet aggregation by inhibiting adenosine diphosphate (promoter of platelet receptor binding) Contranindication avoid in pt w/ liver dysfunction rapidly absorbed after PO admin metabolized in liver half life lengthens w/ repeated dosing decreased renal clearance w/ age Adverse reactions neutropenia Interactions antacids digoxin cimetidine Dosing Stroke prevention in ASA intolerant pts: 250mg BID

Reduce platelet aggregation by inhibiting adenosine diphosphate (promoter of platelet receptor binding) Contranindication avoid in pt w/ liver dysfunction prodrug excreted in urine and feces Adverse reaction bleeding Interactions proton pump inhibitors CYP2C 19 inhibotors Dosing MI prevention: 75 mg daily ST elevation ACS: 300mg daily < 75ys 75mg daily > 75yrs Secondary CVA prevention 75mg Education Separate doses of clopidogrel and PPIs