Heme - FA Pharm p427 - 436 Flashcards
MoA of Heparin
Activates antithrombin, which dec action of IIa (thrombin) and factor Xa.
Why is Heparin safe for use in pregnancy?
Doesn’t cross placenta
How do you test for Heparin fxn?
PTT
name 3 low molecular weight heparins? MoA?
enoxaparin, dalteparin, fondaparinux
Acts predominantly on FXa
5 clinical applications of heparin?
- immediate anticoagulant for PE 2. acute coronary syndrome 3. MI 4. DVT 5. for pregnancy (does not cross placenta)
what are the 5 characteristics of fondaparinux?
- act more on factor Xa 2. better bioavailability 3. 2-4 times longer half life 4. can be administered subcutaneously without lab monitoring 5. not easily reversible
In HIT, what is the pathomech?
development of IgG antibodies against heparin bound platelet factor 4 (PF4).
Antibody-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia.
Ex of direct thrombin inhibitors
Bivalirudin, Argatroban, Dabigatran
When do we use direct thrombin inhibitors
Venous thromboembolism, atrial fibrillation. Can be used in HIT, when heparin is BAD for the patient
How to reverse dabigatran?
What if not avail?
idarucizumab to reverse dabigatran
Consider PCC and/or antifibrinolytics (eg, tranexamic acid) if no reversal agent available.
what is heparin bridging?
heparin is used when starting warfarin which causes transient hypercoagulable state.
initial heparin therapy with warfarin reduces risk of
recurrent venous thromboembolism and skin/tissue necrosis
in warfarin toxicity, what causes the skin/tissue necrosis?
small vessel microthromboses
what gene polymorphism can affect the efficacy of warfarin?
VKORC1 (vit K epxoide reductase complex)
DOC for DVT/PE prophylaxis?
apixaban, rivaroxaban
treatment for CLL?
anti-CD52 (alemtuzumab)
treatment for hairy cell leukemia
cladribine (adenosine analog, 2CDA), pentostatin
explain the mech of thrombolytics
directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibirn clots
what are the 3 clinical applications for thrombolytics?
- early MI 2. early ischemic stroke 3. direct thrombolysis of severe PE
what are the 5 contraindications with thrombolytics?
- active bleeding 2. hx of intracranial bleeding 3. recent surgery 4. known bleeding diatheses (hypocoagulable) 5. severe HPT
what is the antidote for thrombolytics?
aminocaproic acid (antifibrinolytics) platelet transfusions
FFP/PCC
Common side effect of ADP receptor blockers?
What SE is unique to Ticlopidine?
TTP
neutropenia
monoclonal Ab against GP IIb/IIIa?
AbCIXimab (2 times 3 = six)
Name other GpIIb/IIIa (-)’rs
Eptifibatide
Tirofiban
Lomifiban
Orbofiban
Uses of GpIIb/IIIa (-)’rs
unstable angina
percutaneous coronary intervention
MoA of Cilostazol/Dipyridamole
Inc cAMP in platelets –> (-)’n of platelet aggregation
vasodilate ( by (-) Myosin light chain kinase)
Uses of Cilostazol/Dipyridamole
1) Intermittent claudication (Periph vascular disease) 2) Prevention of Stroke/transient ischemic attacks
Dipyridamole - also used for cardiac stress testing
SE of Cilostazol/Dipyridamole
Nausea, headache, facial flushing, hypotension, abdominal pain.
What is the only G2 phase antineoplastic drug and its MOA?
Bleomycin: (+) free radicals, causes DNA strand breakage in tumor cells
Adverse effects of Bleomycin
pulmonary fibrosis, skin hyperpigmentation
Drugs that cause pulmonary fibrosis
Methotrexate,
Nitrofurantoin,
Bleomycin,
Busulfan,
Amiodarone
List 4 drugs that inhibit nucleotide synthesis and their mechanism -
MTX, 5-FU:
dec thymidine synthesis
6-MP:
dec de novo purine synthesis
Hydroxyurea:
inhibits ribonucleotide
reductase
4 cancer drugs that (-) microtubule formation
Paclitaxel
Vinblastine
Vincristine
Eribulin - breast cancer rx
Name the antineoplastic drug which causes BMS with megaloblastic anemia, and the cancer against it is used? MoA?
Cytarabrine used for AML and lymphomas
pyrimidine analogue - DNA chain termination, (-) DNA polymerase
Name the antineoplastic drug which causes pancytopenia, and the cancer against it is used? MoA?
Cytarabrine used for AML and lymphomas
pyrimidine analogue - DNA chain termination, (-) DNA polymerase
Name the cancer drug and its metabolite which is contraindicated in gout therapy? Why?
Azathioprine gets metabolized into 6-Mercaptopurine and both are metabolized by Xanthin oxidase. Allopurinol/ Febuxostat increase 6-MP levels leading to GI and liver tox
Name the cancer drug and MOA that treats abnormal B cells with hair like projections which stain for tartarate resistant acid phosphatase?
Cladribine (2-CDA) is a purine analog which inhibits DNA polymerase and causes DNA strand breakage
DOC for Hairy Cell Leukemia
T5-FU can be used topically for ____ cancer? MOA please
5 Fluorouracil used for Basal cell carcinoma
MOA: 5FU acts as a pyrimidine analog and inhibits thymidylate synthase by converting into a suicide inhibitor 5F-dUMP
Indication (4) of methotrexate and MOA?
MOA: MTX inhibits Dihydrofolate Reductase which indirectly inhibits Thymidylate Synthase
1) MTX treats cancers such as ALL, lymphoma, choricarcinoma,sarcomas
2) Ectopic pregnancy/ Abortion(w/ PGE2 analog)
3) Psoriatic & Rheumatoid Arthritis
4) Tx for Vasculitis
5) IBD
How to recover from the BMS due to MTX? How is this different from 5-FU?
MTX inhibits folate production which can be replenished by leucovorin (Folate analog)
BUT 5-FU forms suicide inhibitor 5F-dUMP (covalent bond with folic acid) and can’t be replenished by leucovorin
This anticancer drug is used for many childhood cancers. Name drug, MOA, and 3 cancers it treats?
Actinomycin D (dactinomycin): intercalates in DNA , (-) RNA synthesis
Cancers
Tx for: 1) Wilms tumor 2) Ewing sarcoma 3) Rhabdomyosarcoma
This antineoplastic has adverse effects to the heart?Name the drug, the toxicity it causes, and the antidote to it?
Doxorubicin/Danorubicin leads to Dilated Cardiomyopathy (DCM)
Cardiotoxicity can be prevented by DEXRAZOXANE (Iron chelator)
MoA of doxo/daunorubicin?
Generate free radicals.
Intercalate in DNA –> breaks in DNA –> dec replication.
Interferes with topoisomerase II
enzyme.
Name 3 cancer drugs that cause pulmonary fibrosis
MTX, Busulfan, Bleomycin
Myelosuppression is a detrimental side effect of antineoplastic therapy. This famous Hodgkin’s Disease drug causes very little bone marrow suppression?
Bleomycin
This alkylating agent has a specific site of cross linking DNA, and require activation? Name the drug, site of crosslinking, and where is it activated?
Cyclophosphamide: crosslinks DNA on the Guanine at the N-7 position. It needs to be bioactivated by the liver.
A 55 yr old lymphoma pt is started on an alkylating agent. A week later he starts complaining of blood in his urine? Name the Dx, and the metabolite of this drug that caused it? How could this have been prevented?
The pt has hemorrhagic cystitis caused by the Cyclophosphamide. Cyclophosphamide gets converted into the toxic metabolite Acrolyn and could have been prevented by administering Mesna
Which anticancer drug can cross BBB and is therefore useful to treat CNS tumors? MoA?
Nitrosoureas (carmustine, lomustine) can pass the BBB. - cross links DNA
Can be used for CNS tumors such as Glioblastoma multiforme
These drugs hyperstabilize polymerized microtubules in M phase - Which cancers are they used for?
Taxanes like paclitaxel are indicated for ovarian and breast tumors
These drugs inhibit microtubule polymerization. Name the two antineoplastics and the cancers they are used for?
Solid tumors, leukemias,
Hodgkin and non-Hodgkin
lymphomas.
How can the Platin caused nephrotoxicity be prevented?
Chloride saline diuresis w/ administeration of Amifostine (free radical scavenger)
The (-tecan) group of drugs mingle with the unwinding of the DNA in tumor cells causing cell cycle arrest. Name the topisomerase inhibited, and two examples with the cancers they treat?
Topoisomerase I is inhibited 1) Irinotecan treats Colon Cancer 2) Topotecan treats Ovarian and sm CC of the lung
MOA of the topside drugs and indications
Etoposide inhibits topoisomerase II
Etwoposide
Used in Tx of: 1) Testicular cancer 2) Sm CC of Lung 3) Leukemia/Lymphoma
This S phase specific antineoplastic drug can be beneficial to Sickle Cell patients? Name the drug and how does it help them?
Hydroxyurea inhibits Ribonucelotide Reductase
Used in Myeloproliferative disorders - CML, PCV
Promotes formation of HbF molecules in SCA pts who are suffering from crisis symptoms of dactylitis
What are the 2 most commonly used glucocorticoids in cancer chemotherapy?
Prednisone, prednisolone
Diabetic retinopathy is treated with what Monoclonal antibody?
Bevacizumab -> anti- VEGF
Tx of Adenocarcinoma of the lung and MOA?
Erlotinib: EGFR tyrosine kinase inhibitor
any non small cell lung cancer
Rituximab inhibits which CD?
CD20
Rituximab = Re2Ximab XX = 20 in latin
Pt that has been treated with BCR-ABL mutation presents with edema, what was the Tx?
Imatinib, dasatinib - Fluid retention.
What drug would you use to treat a 68 year old female with breast ca?
Not a SERM, used primarily in pre-menopausal women ( estrogen levels)
In post menopausal women, we tend to use aromatase inhibitors - anastrozole, letrozole and exemestane
HER-2 (c-erbB2) is what kind of receptor?
tyrosine kinase receptor
Which Tx blocks the binding of estrogen to ER ⊕ cells?
(SERMs)—receptor antagonists in breast
Tx and MOA that treats Metastatic melanoma?
Given with what other class of rx?
Vemurafenib/Dabrafenib
Small molecule inhibitor of BRAF oncogene ⊕ melanoma
VEmuRAF-enib is for V600Emutated
BRAF inhibition.
With MEK inhibitors - Trametinib
Pt undergoing Tx for B-cell neoplastic presents with nonenhancing areas of demyelination on MRI. What was the Tx that caused this?
Rituximab due to developement of progressive multifocal leukoencephalopathy
(Natalizumab also)
Toxicity of Herceptin?
Cardiotoxicity
(Brand name of Trastuzumab)
SE: of EGFR tyrosine kinase inhibitor?
rash, photosen.
(SERMs)—receptor antagonists of the breast causes an incr risk of endometrial cancer?
Tamoxifen
This drugs SE are similar to a dz that is caused by shistosomiasis?
CYclophosphamide–> hemorrhagic cystitis
Pt in chemotherapy acquires hearing loss, what was the Tx?
Cisplatin/Carboplatin
