Pharmacology: Heme/Onc Flashcards
Heparin
What lab value do you monitor?
Anti-coagulant; binds and enhances anti-thrombin III activity (induces conformational change that allows ATIII to rapidly inhibit thrombin [IIa], Xa, IXa, VIIa)
- Rapid effect
- Does not work on thrombin already bound to fibrin
- Monitor PTT
SE: excessive bleeding, HIT, osteoporosis, hypersensitivity, use low doses to decr risk from thrombosis from reduced levels of ATIII
Protamine sulfate
Reverses heparin action
- positively charged drug that binds negatively charged heparin
Enoxaparin
Monitor labs?
Anticoagulant; LMWH
- More Xa effects
- No labs to monitor
Lepirudin
Anticoagulant; direct thrombin inhibitor
Alternative for anticoaguation in HIT
Bivalirudin
Anticoagulant; direct thrombin inhibitor
Alternative for anticoaguation in HIT
Warfarin (Coumadin)
Anticoagulant; inhibits epoxide reductase (gamma-carboxylation of Vit K dependent clotting factors)
- Cyt P450 metabolism
- Long half-life
SEs: bleeding, teratogenic, drug-drug reactions, skin/tissue necrosis! (From pro-thrombotic state when anti-coag PC/PS initially decreases before clotting factors)
Fondaparinux
Synthetic pentasaccharide, selective Factor Xa inhibitor (NOT thrombin)
Streptokinase
Thrombolytic
Complexes with plasminogen and the resulting complex activates plasminogen to plasmin conversion
- Early MI, early ischemic stroke
SEs: Bleeding! (Don’t use in active bleeding, ICH, recent surgery, bleeding d/o, severe hypertension
Urokinase
Thrombolytic
Directly activates plasminogen to plasmin
tPA
Thrombolytic
Directly activates plasminogen to plasmin
Alteplase
Another name for tPA!
Thrombolytic
Directly activates plasminogen to plasmin
Anisoylated plasminogen streptokinase activator complex (APSAC)
Thrombolytic, already activated complex
Aminocaproic acid
Inhibits fibrinolysis by preventing plasminogen activation
SE: intravascular thrombosis
Tranexamic acid
Inhibits fibrinolysis by preventing plasminogen activation
SE: intravascular thrombosis
Aspirin
What does the BT, PT, PTT look like?
Anti-platelet (low dose), anti-pyretic and analgesic (med dose), anti-inflammatory (high dose)
- Acetylates and irreversibly inhibits COX-1 and -2
- Prevents AA –> TXA2 conversion (which normally mediates plt aggregation) and AA –> PGs
- Increases BT
- No effect on PT/PTT
SEs:
- GI: gastric ulcers, bleeding
- Renal: RF, AIN
- Hyperventilation, tinnitus (CN VIII)
- Reye’s syndrome in kids (rash, encephalitis, fatty liver)
Clopidogrel
Anti-platelet
Irreversible blockade of ADP receptors, prevent gpIIb/IIIa expression decr fibrinogen binding
Ticlopidine
Anti-platelet
Irreversible blockade of ADP receptors, prevent gpIIb/IIIa expression decr fibrinogen binding
SE: Neutropenia!
Clopidogrel vs. ticlopidine
Ticlopidine can cause neutropenia
Cilostazol
PDE III inhibitor (which normally degrade cAMP), increases cAMP and prevents platelet aggregation
Uses: intermittent claudication, coronary vasodilation, prevent stroke/TIA with ASA, ppx angina
SEs: nausea, HA, facial flushing, hypotension,abdominal pain
Dipyridamole
PDE III inhibitor (which normally degrade cAMP), increases cAMP and prevents platelet aggregation
Uses: same as cilostazol, also used in pharmacologic stress testing
Abiciximab
Antiplatelet
Monoclonal antibody against gp IIb/IIIa on activated platelets
Eptifibaride
Antiplatelet
Peptide inhibitor of gp IIb/IIIa
Tirofiban
Antiplatelet
Non-peptide inhibitor of gp IIb/IIIa
Hirudin
Direct thrombin inibitor
Argatroban
Direct thrombin inibitor
Methotrexate
Antimetabolite
- Folic acid analog, inhibits dihydrofolate reductase leading to decreased formation of dTMP and decreased DNA and protein synthesis
- SEs: myelosuppression (leucovorin rescue), macrovesicular fatty liver change, mucositis, teratogenic
5-fluorouracil
Antimetabolite
- Pyrimidine analog, bioactivated to 5F-dUMP, which covalently complexes folic acid. Complex inhibitis thymidylate synthase
- Synergistic with MTX
- SEs: myelosuppression, not reversible with leucovorin; photosensitivity
6-mercaptopurine
Antimetabolite
- Leukemia/lymphoma, but NOT CLL or Hodgkin’s
- XO metabolism, increased toxicity with allopurinol
6-thioguanine
Antimetabolite
- ALL
- Ok with allopurinol
Cytarabine (ara-C)
Antimetabolite
- Pyrimidine analog
- Leucovorin
2. Allopurinol
- Myelosuppression by MTX can be rescued via leucovorin, but not with 5-FU
- 6-MP should not be used with allopurionol (metabolized by XO), but 6-TG is ok
What other things can MTX be used for (other than leukemia/lymphoma)?
- Other cancers: choriocarcinoma, sarcomas (e.g. osteosarcoma)
- Noncancers: abortion, ectopic pregnancy, RA, psoriasis
Dactinomycin
What is is used for?
Antitumor antibiotic
- DNA intercalation
Childhood tumors!! (Ewing’s, Wilms)
Doxorubicin
Antitumor antibiotic
- FR generation, non-covalent DNA intercalation leading to DNA breaks and decreased replication
Daunorubicin
Antitumor antibiotic
- FR generation, non-covalent DNA intercalation leading to DNA breaks and decreased replication
Dexrazoxane
Iron chelating agent
Prevent cardiotoxicity with doxo/daunorubicin therapy
Bleomycin
Antitumor antibiotic
- FR generation, non-covalent DNA intercalation leading to DNA breaks and decreased replication
Etoposide (VP-16)
Antitumor antibiotic
Inhibits topoisomerase II, increases DNA degradation
- For small cell carcinoma of lung and prostate, testicular carcinoma
SEs: myelosuppresion, alopecia, GI irritation
Teniposide
Antitumor antibiotic
Inhibits topoisomerase II, increases DNA degradation
- For small cell carcinoma of lung and prostate, testicular carcinoma
SEs: myelosuppresion, alopecia, GI irritation
Cyclophosphamide
Alkylating agent
- Covalently cross-link (interstrand) DNA at guanine N-7
- Requires liver bioactivation
Ifosfamide
Alkylating agent
- Covalently cross-link (interstrand) DNA at guanine N-7
- Requires liver bioactivation
Mesna
For ppx of hemorrhagic cystitis by cyclophosphamide and ifosfamide
Carmustine
Nitrosourea/alkylating agent
- Requires bioactivation
- Can cross BBB, use for brain tumors! (GBM)
SEs: CNS toxicity–dizziness, ataxia
Lomustine
Nitrosourea/alkylating agent
- Requires bioactivation
- Can cross BBB, use for brain tumors! (GBM)
SEs: CNS toxicity–dizziness, ataxia
Semustine
Nitrosourea/alkylating agent
- Requires bioactivation
- Can cross BBB, use for brain tumors! (GBM)
SEs: CNS toxicity–dizziness, ataxia
Streptozocin
Nitrosourea/alkylating agent
- Requires bioactivation
- Can cross BBB, use for brain tumors! (GBM)
SEs: CNS toxicity–dizziness, ataxia
Busulfan
Alkylating agent
- CML
SEs: pulmonary fibrosis, hyperpigmentation
Vincristine
Microtubule inhibitor
- Bind tubulin in M phase and inhibit microtubule polymerization
- Mitotic spindle cannot form
SE: Neurotoxic (areflexia, peripheral neuritis), paralytic ileus
Vinblastine
Microtubule inhibitor
- Bind tubulin in M phase and inhibit microtubule polymerization
- Mitotic spindle cannot form
SE: Myelosuppression
Paclitaxel
Microtubule inhibitor
- Hyperstabilizes polymerized microtubules in M-phase so that mitotic spindle cannot form
- Ovarian and breast cancers
SEs; Myelosuppression and hypersensitivity
Cisplatin
Cross-links DNA
- SEs: Nephrotoxicity, ototoxicity
Carboplatin
Cross-links DNA
- SEs: Nephrotoxicity, ototoxicity
Amifostine
FR scavenger
Use to prevent nephrotoxicity with -platin chemotherapy
Choride diuresis
A method of forced diuresis to enhance excretion of drugs in urine
Used to prevent nephrotoxicity with -platin chemotherapy
e.g. AlCl.. makes urine more acidic
Hydroxyurea
Inhibits ribonucleotide reductase and decreases DNA snythesis in S phase
Also increases HbF in SCD
- SEs: myelosuppression, GI upset
Prednisone
May trigger apoptosis
Tamoxifen
SERM
Raloxifen
SERM
Trastuzumab
aka Herceptin
Monoclonal ab against HER-2 (erb-b2), a tyrosine kinase
- SE: cardiotoxic
Imatinib
aka Gleevec
For CML, bcr-abl tyr kinase inhibitor
- SE: fluid retention
Rituximab
Monoclonal ab against CD20 in B cells
- Used for nHL, RA
