Heme Drugs Flashcards
Heparin
- immediate effect
- use: coronary syndrome, PE, MI, DVT, ok for pregnancy
- binds endothelial surface and accelerates antithrombin IIIa to inhibit 2a,9a,10a,11a,12a
- increases PTT
- short 1/2 life
- injection only
- adverse: HIT, osteoporosis, hyperkalemia
Enoxaprin (LMWH)
- more bioavailability, longer 1/2 life, easier dosing
- less risk than heparin
- inhibits 10a more than 2a
Warfarin
- slow onset, limited by 1/2 life
- acts on liver, oral, must monitor pt
- ok for chronic use, NOT ok for pregnancy
- impairs post translational mods of Factors 2,7,9,10
- reverse: use Vitamin K1 , 4 factor prothrombin complex concentrates
Aspirin
- blocks cyclooxygenase, lowers TXA2 levels, inhibits platelet aggregation
- use: early MI, ischemic stroke
- adverse: bleeding, GI upset
Abciximab
- use: unstable angina, percutaneous coronary intervention
- blocks fibrinogen receptor (GP 2b,3a) on activated platelets, blocks aggregation
- IV use, rapid acting
- adverse: bleeding, thrombocytopenia
Clopidigrel, ticagrelor, prasugrel
- ADP(P2Y12) receptor antagonists
- use: acute coronary syndrome, coronary stenting, decrease stroke risk
- prevents expression of GP 2b,3a on platelet surface
- oral use, often use with aspirin
- adverse: bleeding, thrombocytopenia
Dipyrimidamole, Cilostazol
- PDE inhibitors
- use: intermittent claudication, coronary vasodilation, TIA, stroke prevention
- increases cAMP, prevents aggregation, vasodilation
- adverse: bleeding, nausea, headache, hypotension, abdominal pain
Bivalirudin, argatroban, dabigatran
- thrombin inhibitors
- directly inhibit free and clotted thrombin, competitively bind active site
- use:venous thrombosis, prevent stroke in a fib, use in HIT
- dabigatran is only oral
- adverse: bleeding, use of P-GP inhibitors at same time can increase levels of bivalirudin and argatroban
Idarucizumab
- monoclonal antibody
- reversal of dabigatran anticoagulant effects
Rivaroxiban, apixaban
- 10a inhibitors
- directly inhibit factor 10a by binding it
- oral
- use: prophylaxis for DVT, PE, stroke with a fib
- adverse: bleeding, use of p-GP drugs could increase levels
- Rivaroxiban absorption is mediated by p-GP transporter
Fondaparinux
- 10a inhibitor
- inactivated 10a indirectly by accelerating ATIII, no action on 2a
- injection
- no issues with HIT, no PF4 antibody is formed
- long 1/2 life
- adverse: bleeding
Alteplase (tPA), reteplase (rTPA), tenecteplase (TNK-tPA)
- fibrinolytics, plasminogen activators
- early MI, ischemic stroke, direct thrombolysis of severe PE
- directly or indirectly aid the conversion of plasminogen to plasmin which then cleaves thrombin and fibrin clots
- no effect on platelet count
- adverse: bleeding, can reverse with antifibrinolytics, platelet transfusion, FFP, PCC
Tranexamic acid, Aminocaproic acid
- antifibrinolytic
- reversible blockade of lysine binding sites on plasminogen molecules to inhibit fibrin formation
- use: reduce perioperative bleeding, prevent blood loss from trauma, postpartum hemorrhage, prophylaxis for hemophilia, heavy periods
- adverse: bradyarrhythmia, hypotension, seizures
Cytarabine and anthracycline
-induction: 7 days + 3 days
-extremely toxic therapy
-consolidation: high dose cytarabine, given 3-4 times after remission
toxicities: Anthracycline=cardiac failure
Cytarabine=cerebellar toxicity
Imatinib, Dasatinib, Nilotinib
-tyrosine kinase inhibitors target BCR-ABL1 protein and block activity
-toxicities:
Imatinib- fluid retention, muscle pain/cramps, GI disturbance
Dasatinib- 20-25% pleural effusions, rare pulmonary arterial hypertension
Nilotinib- vascular events, peripheral arterial occlusive disease, CAD, hyperglycemia, hypercholesterolemia
Vincristine
- mitotic spindle inhibitors
- bind tubulin and disrupt mitotic spindle and cause metaphase arrest
- metabolized by CYP3A4
- causes peripheral neuropathy, GI motility issues
- used for ALL to induce remission and as maintenance therapy
Methotrexate
-folic acid analog, actively transported into cells
-high doses distribute to CNS
-oral and IV
Toxicity: hepatotoxic, nephrotoxic
-use to eradicate ALL below level of detection
Mercaptopurine
- purine analog, does not bind DNA
- distributes to CNS
- inhibits de novo purine synthesis
- hepatotoxic
- use for ALL eradication of disease
Cyclophosphamide
-alkylating agent, binds DNA directly
-oral or IV
N,V,myelosuppression, hemorrhagic cysts,alopecia
Can cause late secondary leukemia
-use for eradication of ALL
Asparaginase
- use for remission induction in ALL
- can cause pancreatitis, DIC, hyperglycemia, hepatotoxicity
Glucocorticoids
- use for remission induction and maintenance therapy in ALL
- hyperglycemia, mood changes, muscle wasting, ulcers
- exposure can cause avascular necrosis esp. in young pts
Bleomycin
- use for classic Hodgkin lymphoma
- antineoplastic antibiotic
- interferes with topoisomerase II, transcription and replication
- does not suppress bone marrow
- inactivated except in skin and lung tissue, can cause skin lesions, hyperpigmentation, pulmonary fibrosis
Rituximab
- prototype for monoclonal antibody
- anti-CD20
- used in combination with chemo
- use for CLL
Fludarabine
- purine analog
- specific toxicity: severe marrow toxicity, AI hemolytic anemia, ITP
- use for CLL
