Pharm Hemato/onco Flashcards
Heparin (MOA)
Activates antithrombin (which decrease action primarily of factors IIa (thrombin) and Xa)
Heparin (clinical use) : in the intrinsic
Pulmonary embolism
Acute coronary syndrome
MI
DVT
(Used in pregnancy= does not cross placenta)
Monitor PTT
Heparin Adverse effects:
Bleeding
Heparin induced thrombocytopenia (HIT)
Osteoporosis (long term use)
HIT type 1:
Mild (pc > 100,000)
Non immunologic drop in platelet count.
Highest risk w unfractionated heparin
HIT type 2:
Development IgG ab against (PF4)
5-10 days after heparin administration
Ab- heparin complex binds and activates platelets —- removal by splenic macrophages. Decrease platelet count.
Low molecular weight heparins: Examples
Enoxaparin, dalteparin:
Act mainly on factor Xa
Fondaparinux: acts only on factor Xa
LMWHs: notes
Undergo renal clearance: use w caution with renal insufficiency
Can be administered subscutaneosly
No lab monitoring required
Warfarin (MOA):
Inhibits vitamin K epoxide reductase
Inhibitions of Vit K dependent gamma carboxylations of clotting factors: 2,7,9,10 and protein C,S
Extrinsic pathway: high PT
Warfarin (clinical use)
Chronic anticoagulation (venous thromboembolism prophylaxis and prevention of stoke in AF)
Not for pregnant patients
Monitor PT/INR
Warfarin (adverse effects)
Bleeding
Teratogenic
Skin/tissue necrosis
Warfarin reversal:
Vitamin K
For rapid reversal: FFP, PCC
Warfarin administration
Oral
Heparin administration
Parenteral (IV, SC)
Site of action Warfarin:
Liver
Site of action of heparin:
Blood
MOA:
Bivalirudin
Argatroban
Dabigatran
Directly inhibit thrombin (factor IIa)
Clinical use of:
Bivalirudin
Argatroban
Dabigatran (oral)
Venous thromboembolism
Atrial fibrillation
Can be used in HIT
Does not require lab monitoring
MOA:
ApiXAban
EndoXAban
RivaroXAban
Directly inhibit factor Xa
Clinical use:
ApiXAban
EndoXAban
RivaroXAban
Tx and prophylaxis for DVT and PE
Stroke prophylaxis in pte with AF
Adverse effects:
ApiXAban
EndoXAban
RivaroXAban
Bleeding
Reverse with andeXAnet alfa
Dabigatran reversal:
Idarucizumab
Antiplatelets (MOA): Aspirin
Blocks COX —> decrease TXA2 release
Aspirin (Adverse effects):
Gastric ulcer
Tinnitus
Allergic reaction
Renal injury
Antiplatelets (MOA):
Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine
Block ADP (P2Y12) Receptor:
Decrease ADP- induced expression of GpIIb/IIIa
Antiplatelets (AE):
Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine
Neutropenia (ticlopidine)
TTP
Antiplatelets (MOA):
Abciximab
Eptifibatide
Tirofiban
A GpIIb/IIIa Receptor antagonist , inhibits binding of this receptor to fibrinogen.
Antiplatelets (clinical use):
Abciximab
Eptifibatide
Tirofiban
Unstable angina
Percutaneous coronary intervention
Antiplatelets (AE)
Abciximab
Eptifibatide
Tirofiban
Bleeding
Thrombocytopenia
Antiplatelets (MOA):
Cilostazol
Dipyridamole
Block phosphodiesterase —> decrease cAMP in platelets
Antiplatelets (CU):
Cilostazol
Dipyridamole
Intermittent claudication
Stroke prevention
Cardiac stress testing
Prevention of coronary stent restenosis
Antiplatelets (AE):
Cilostazol
Dipyridamole
Nausea
Headache
Facial flushing
Hypotension
Abdominal pain
Thrombolytics: MOA
Alteplase
Reteplase
Streptokinase
Tenecteplase
Aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots.
Aumenta PT and PTT, no change in platelet count
Antifibrinolytics
Aminocaproic acid
Tranexamic acid
Antitumor antibiotics: MOA
Bleomycin
Induce free radical formation = breaks in DNA strands
Antitumor antibiotics: CU
Bleomycin
Testicular cancer
Hodgkin lymphoma
Antitumor antibiotics: AE
Bleomycin (specific G2/M phase)
Pulmonary fibrosis
Skin hyperpigmentation
Antitumor antibiotics: MOA
Dactinomycin (actinomycin D)
Intercalates into DNA, preventing RNA synthesis
Antitumor antibiotics: CU
Dactinomycin (actinomycin D)
Wilms tumor
Ewing sarcoma
Rhabdomyosarcoma
Antitumor antibiotics: AE
Dactinomycin (actinomycin D)
Myelosuppression
Antitumor antibiotics: MOA
Anthracyclines:
Doxorubicin
Daunorubicin
Generate free radicals
Intercalate in DNA- breaks in DNA -> decrease replication.
Inhibits topoisomerase II
Antitumor antibiotics: CU
Anthracyclines:
Doxorubicin
Daunorubicin
Solid tumors
Leukemia
Lymphomas
Antitumor antibiotics: AE
Anthracyclines:
Doxorubicin
Daunorubicin
Dilated cardiomyopathy (prevent w/ dexrazoxane)
Myelosuppression
Alopecia
Platinum compounds: MOA
Cisplatin
Carboplatin
Oxaliplatin
Cross link DNA (cell cycle nonspecific)
Platinum compounds: clinical use
Cisplatin
Carboplatin
Oxaliplatin
Solid tumors: testicular, bladder, ovarian, GI, lung, lymphomas
Platinum compounds: AE
Cisplatin
Carboplatin
Oxaliplatin
Nephrotoxicity (fanconi synd)
Peripheral neuropathy
Ototoxicity
Rituximab (MOA)
Monoclonal ab against the CD20 antigen
Warfarin can be monitored with
INR
an Prothrombin time (PT)
Anthracyclines (doxorubicin) MOA and SE:
Binds w topoisomerase II to cleave DNA
Binds w iron to generate free radicals
Dilated cardiomyopathy
Bleomycin MOA and SE :
Induces free radical formation
Pulmonary fibrosis
Cisplatin (MOA) and (SE)
Cross- link DNA to inhibits DNA synthesis.
Nephrotoxicity
Ototoxicity
Peripheral neuropathy
Cyclophosphamide MOA and SE:
Cross-link DNA to inhibit DNA synthesis
Hemorrhagic cystitis
Bladder cancer
Paclitaxel MOA and SE:
Inhibits microtubule disassembly
Neuropathy
Vincristine/ vinblastine MOA/ SE:
Binds beta-tubulin to inhibit microtubule formation
Neuropathy
Trastuzumab (MOA):
Is for HER2 + cancer
Its binds to a portion of the extracellular domain of HER2 and prevents activation of a transmembrane tyrosine kinase.
This downregulates cellular proliferation and promotes apoptosis.
Emicizumab (for hemophilia A) MOA:
Mimics the activity of factor 8 by binding to both factor 9a and factor 10, bringing them into close proximity to allow for factor 10 activation.
Heparin coagulation changes
Thrombin time: prolonged
PTT: prolonged
Activity of factor Xa: decreased
CYP450 inhibitors
Antibiotics (metronidazole, macrolides)
Azole
Amiodarone
Cimetidine
Grapefruit
CYP450 inducers
Carbamazepine
Phenytoin
Phenobarbital
Rifampin
St. John wort
6-mercaptopurine (6-MP) (pro drug: azathioprine) is inactivates by the following enzymes:
Xanthine oxidase and thiopurine methyltransferase