Antiplatelet drugs

Aspirin

Aspirin works by irreversibly acetylating platelet cyclooxygenase 1 (COX-1) resulting in decreased production of thromboxane A2.

Aspirin also irreversibly acetylates COX-2 when given at high doses which results in an anti-inflammatory effect.

P2Y12 Inhibitors

Examples include clopidogrel, prasugrel and ticagrelor as well as ticlodipine. They work by binding to the P2Y12 component of ADP receptors on platelets resulting in inhibition of platelet aggregation.

Phosphodiesterase inhibitors

Dipyridamole and Cilostazol also cause inhibition of platelet aggregation and they work by inhibiting phosphodiesterase activity which leads to elevated cAMP.

Glycoprotein IIb/IIIa inhibitors

Examples include abciximab, eptifibatide, and tirofiban. These work by inhibiting binding of platelet glycoprotein IIb/IIIa with fibrinogen and fibronectin.

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Chronic Myeloid Leukemia (CML)

Quick Review Patient is often older, and can no symptoms or have B symptoms (night sweats, etc), fatigue, and weight loss (caused by early satiety due to enlarged spleen). On physical exam, an enlarged spleen can be palpated. CBC shows very high WBC count (typically >100,000) with elevated basophils on differential. Peripheral smear shows early, immature neutrophil precursors (myelocytes, metamyelocytes) as well as many basophils. It is important for CML to know the details of the genetic abnormality because it relates to the treatment. CML is due to a translocation of BCR and ABL on chromosomes 9 and 22 resulting a fusion BCR-ABL gene that produces a tyrosine kinase that is always active. The treatment of choice is a tyrosine kinase inhibitor e.g. imatinib. They work to suppress the tyrosine kinase and can induce disease remission. Relevant Images Immature neutrophil precursors on peripheral smear BCR-ABL translocation

Chemotherapy

Terminology Adjuvant therapy - given in addition to standard therapy Consolidation therapy - given after induction therapy with multidrug regimens to further reduce tumor burden Induction therapy - initial dose of treatment to rapidly kill tumor cells and send the patient into remission Maintenance therapy - given after induction and consolidation therapies or after the initial standard therapy to kill any residual tumor cells and keep the patient in remission Neoadjuvant therapy - given before the standard therapy for a particular disease Remission - less than 5% tumor burden Salvage therapy - given when standard therapy fails Adjuvant therapies in various cancers Metastasis to bone - bisphosphonates (e.g. zoledronic acid) are given to prevent lytic lesions and pathologic fractures as well as malignant hypercalcemia. Bisphosphonates work by inhibiting osteoclasts and thereby preventing bone breakdown. Breast cancer Tamoxifen , a selective estrogen recep

Acute Myeloid Leukemia (AML)

Quick Review Patient is an adult (usually older, but can also be younger) with fatigue (due to anemia) and bleeding (due to thrombocytopenia) and on CBC there is decreased hemoglobin, decreased platelets, and WBC varies (can be normal, increased or decreased). LDH will be elevated. The most important form of AML to know is acute promyelocytic leukemia (APML). On peripheral smear, AML presents with myeloblasts with Auer rods. Bone marrow biopsy will show myeloid blasts, for APML this would be atypical promyelocytes. In AML, the bone marrow is crowded with immature myeloid cells ("blasts") preventing development of other cell types (platelets, RBCs, normal WBCs). These myeloblasts are also present in the peripheral blood in large numbers. This is why patients have fatigue (anemia), bleeding/ bruising (thrombocytopenia), increased infections (granulocytopenia). APML can present with DIC (disseminated intravascular coagulation) which results in elevated PT and aPTT and re

pathology

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