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Rosenstock et al., 2019) investigating the safety and efficacy of incretin-based drugs have provided diverse interpretations and provocative intellectual curiosities regarding the biology of incretin hormones and incretin-based drugs, specifically focusing on pleiotropic effects

It inhibits: Vitamin K epoxide reductase (VKORC1) Activation of Factors II, VII, IX, X Protein C & S (important for early hypercoagulability!) Effect monitored by INR Dosing (very exam & practice relevant) Initial dose: Usually 5 mg once daily Lower initial dose (23 mg) if: Elderly Liver disease Heart failure High bleeding risk Target INR: Most indications (AF, DVT, PE): 2.0 3.0 Mechanical mitral valve: 2.5 3.5 Full anticoagulant effect takes 35 days Types / Form Oral drug Racemic mixture: S-warfarin more potent R-warfarin longer half-life Important clinical pearl Initial hypercoagulable state Because Protein C & S fall first risk of: Warfarin-induced skin necrosis Solution: Bridge with heparin at initiation Antidote & reversal (VERY high-yield) Antidote: Vitamin K (Phytonadione) Situation Management INR high, no bleeding Oral Vitamin K 12.5 mg Serious bleeding IV Vitamin K 510 mg Life-threatening bleeding Vitamin K + PCC (preferred) or FFP PCC = Prothrombin Complex Concentrate (fastest reversal) Side effects Bleeding (most common) Skin necrosis (Protein C deficiency) Purple toe syndrome Teratogenic contraindicated in pregnancy Many drug & food interactions Foods rich in vitamin K (spinach, broccoli) effect Contraindications Pregnancy Active bleeding Severe liver disease Poor compliance (needs frequent INR monitoring) Take-home message Warfarin is: Powerful Cheap Effective But requires knowledge, monitoring, and respect Mastering warfarin = mastering clinical pharmacology & patient safety

This laid the groundwork for a collaboration with Heinrich and Wilson, who were working on the rat pancreatic preproglucagon in Habener's laboratory

Standard deodorants only mask the odor with perfumes