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USMLE Pharmacology > Hematology > Flashcards

Hematology Flashcards

1
Q

Cromolyn sodium

A

Prevents mast cell degranulation

Used for asthma prophylaxis

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2
Q

Heparin

A

Cofactor for the activation of antithrombin III
Decreases thrombin and factor Xa
SHORT half-life

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3
Q

Heparin antidote

A

Protamine sulfate

Positively charged molecule that binds negatively charged heparin

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4
Q

Low molecular weight heparins (2)

A

Enoxaparin
Dalteparin

Act more on factor Xa
Better bioavailability
2-4x longer half-life
Administered subcutaneously
No lab monitoring
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5
Q

Is heparin used in pregnancy?

A

YES

Does not cross placenta

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6
Q

Test used to monitor heparin?

A

PTT

Intrinsic pathway

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7
Q

Protamine sulfate

A

Antidote for heparin

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8
Q

Direct thrombin inhibitors (2)

A

Argatroban
Bivalirudin

Derivatives of hirudin
Inhibit thrombin directly
Used instead of heparin for anticoagulating patients with HIT

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9
Q

Warfarin

A

Inhibits Vitamin K epoxide reductase
Interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors
Metabolized by cytochrome P450 pathway
LONG half-life

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10
Q

What are the vitamin K dependent clotting factors?

A

II, VII, IX, X

Proteins C and S

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11
Q

Test used to monitor warfarin?

A

PT/INR

Extrinsic pathway

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12
Q

Is warfarin used in pregnancy?

A

NO = teratogenic

Can cross the placenta

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13
Q

Warfarin antidote?

A

Vitamin K

Fresh frozen plasma (rapid reversal)

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14
Q

Serious complication of warfarin toxicity?

A

Warfarin skin/tissue necrosis

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15
Q

Direct factor Xa inhibitors (2)

A 
Apixaban
Rivaroxaban (oral)

Bind and directly inhibit activity of factor Xa
Oral agents = no coagulation monitoring

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16
Q

Direct factor Xa inhibitor antidote?

A

NONE!!!

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17
Q

Heparin uses

A

Immediate anticoagulation for PE, ACS, MI, DVT

Pregnancy

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18
Q

Warfarin uses

A

Chronic anticoagulation after STEMI, venous thromboembolism prophylaxis, prevention of stroke in a fib
NOT used in pregnancy

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19
Q

Apixaban and rivaroxaban uses

A

Tx and prophylaxis DVT and PE (rivaroxaban)

Stroke prophylaxis in patients with a fib

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20
Q

Thrombolytics (3)

A

Alteplase (tPA)
Reteplase (rPA)
Tenecteplase (TNK-tPA)

Directly or indirectly aid conversion plasminogen to plasmin, which cleaves thrombin and fibrin clots

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21
Q

PT/PTT and platelet count with thrombolytics?

A

Increased PT/PTT

Normal platelet count

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22
Q

Thrombolytic antidote?

A

Aminocaproic acid

Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies

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23
Q

Thrombolytic uses

A

Early MI or ischemic stroke

Direct thrombolysis of severe PE

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24
Q

Aspirin MOA

A

Irreversibly inhibits cyclooxygenase (covalent acetylation)

Platelets cannot synthesize new enzyme = effect lasts until new platelets are produced

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25
How does ASA irreversibly inhibit COX?
Covalent acetylation
26
Aspirin labs
Increased bleeding time Decreased TXA2 and prostaglandins NORMAL PT/PTT Affects primary hemostasis
27
Aspirin overdose acid/base
Respiratory ALKALOSIS initially | superimposed metabolic ACIDOSIS later
28
Aspirin toxicity
Gastric ulceration Tinnitus Chronic use = acute renal failure, interstitial nephritis, upper GI bleed
29
Should you give ASA to a child?
NO = can cause Reye syndrome!
30
ADP (P2Y12) receptor inhibitors (5)
``` Clopidogrel (Plavix) Ticlopidine Prasugrel Ticagrelor Cangrelor = reversible ``` Inhibit platelet aggregation by irreversibly blocking ADP receptors Inhibit fibrinogen by preventing GPIIb/IIIa from binding fibrinogen
31
P2Y12 inhibitor toxicity
Neutropenia (ticlopidine) | TTP/HUS may be seen
32
Cilostazol, dipyridamole MOA? Toxicity?
Phosphodiesterase III inhibitors Block cAMP --> AMP = increased cAMP in platelets, which inhibits platelet aggregation Vasodilators Toxicity = nausea, headache, facial flushing, hypotension, abdominal pain
33
GPIIb/IIIa inhibitors (3) | Toxicity?
Abciximab ("six") Eptifibatide Tirofiban Bind to GPIIb/IIIa on activated platelets and prevent aggregation = prevent fibrinogen cross linking Toxicity = bleeding, thrombocytopenia
34
Antimetabolites
Methotrexate (MTX) 5-fluorouracil (5-FU) Cytarabine (arabinofuranosyl cytidine) = ara-C Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) All are S-PHASE specific
35
Methotrexate
Folic acid analog Inhibits dihydrofolate reductase (decrease dTMP, DNA, protein synthesis) ``` Toxicity: Myelosuppression (reversible with LEUCOVORIN [folinic acid] "rescue") Macrovesicular fatty change in liver Mucositis Teratogenic ```
36
Methotrexate "rescue"
Leucovorin (folinic acid)
37
5-FU
Pyrimidine analog bioactivated to 5F-dUMP = covalently complexes folic acid Inhibits thymidylate synthase (decrease dTMP, DNA, protein synthesis) Toxicity: Myelosuppression "Rescue" with URIDINE Photosensitivity
38
5-FU "rescue"
Uridine
39
Cytarabine
Pyrimidine analog Inhibition of DNA polymerase ``` Toxicity: Leukopenia Thrombocytopenia Megaloblastic anemia (folate deficiency) (CYTarabine = panCYTopenia) ```
40
Azathioprine, 6-MP, 6-TG
Purine (thiol) analogs = decrease de novo purine synthesis Activated by HGPRT Toxicity: bone marrow, GI, liver Increased toxicity with allopurinol (azathioprine and 6-MP metabolized by xanthine oxidase)
41
Antitumor antibiotics
Dactinomycin (actinomycin D) Doxorubicin (Adriamycin), daunorubicin Bleomycin
42
Dactinomycin
Intercalates in DNA Used for childhood tumors Toxicity = myelosuppression
43
Doxorubicin, daunorubicin
Generate free radicals Intercalate in DNA = breaks = decreased replication Toxicity = CARDIOTOXICITY (dilated cardiomyopathy), myelosuppression, alopecia
44
Agent used to reduce cardiotoxicity from doxorubicin and daunorubicin
Dexrazoxane = iron chelating agent
45
Bleomycin
Induces free radical formation = breaks in DNA | Toxicity = PULMONARY FIBROSIS, skin changes, mucositis; minimal myelosuppression
46
Alkylating agents
Cyclophosphamide, ifosfamide Nitrosoureas (carmustine, lomustine, semustine, streptozocin) Busulfan
47
Enzymes inhibited by lead
ALA dehydratase | Ferrochelatase
48
Lead poisoning treatment
Dimercaprol and EDTA | Succimer used for chelation for kids
49
Sideroblastic anemia treatment
Pyridoxine (B6, cofactor for delta-ALA synthase)
50
Cyclophosphamide, isofosfamide
Covalent cross-links DNA at guanine N7 Bioactivation by liver Toxicity: Myelosuppression Hemorrhagic cystitis (prevent with mesna)
51
Agent used to prevent hemorrhagic cystitis due to cyclophosphamide
Mesna | Thiol group binds toxic metabolites
52
Nitrosoureas
Carmustine, lomustine, semustine, streptozocin Cross BBB to CNS, cross links DNA Treatment for brain tumors Toxicity = CNS; convulsions, dizziness, ataxia
53
Busulfan
Cross-links DNA CML; ablates bone marrow before transplant Toxicity = myelosuppression, pulmonary fibrosis, hyperpigmentation
54
Vincristine, vinblastine
Vinca alkaloids, bind B-tubulin INHIBITS POLYMERIZATION Prevents mitotic spindle formation (M phase arrest) Toxicity: Vincristine = neurotoxicity (areflexia, peripheral neuritis), paralytic ileus Vinblastine = bone marrow suppression
55
Paclitaxel and other taxols
Hyperstabilize polymerized microtubules in M phase so spindle cannot break down (prevent anaphase) INHIBITS DEPOLARIZATION "Taxing to stay polymerized" Toxicity = myelosuppression, alopecia, hypersensitivity
56
Cisplatin, carboplatin
Non-classical alkylating agents Cross-link DNA Nephrotoxicity and acoustic nerve damage Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis
57
Etoposide, tenoposide
Topoisomerase II inhibitors = increase DNA degradation | Myelosuppression, GI irritation, alopecia
58
Irinotecan, topotecan
Topoisomerase I inhibitors = prevent DNA unwinding and replication Severe myelosuppression, diarrhea
59
Hydroxyurea
Inhibits ribonucleotide reductase = decreases DNA synthesis (S-phase specific) Bone marrow suppression, GI upset
60
Prednisone, prednisolone, dexamethasone
Used to decrease adverse effects of chemotherapeutics May trigger apoptosis = inhibits lymphocyte proliferation Immunosuppressive Toxicity = Cushing syndrome sx (WG, central obesity, muscle breakdown, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis)
61
Tamoxifen, Raloxifene
Selective estrogen receptor modulators (SERMs) = antagonists in breast and agonists in bone Block binding of estrogen to ER + cells Tamoxifen = breast cancer; toxicity = partial agonist in endometrium (increased risk cancer), hot flashes Raloxifene = osteoporosis; not an endometrial antagonist
62
Trastuzumab
Herceptin Monoclonal AB against HER-2 (c-erbB2) = tyrosine kinase receptor = kills breast cancer cells that overexpress HER-2 Cardiotoxicity = damages the heart
63
Imatinib
Gleevec Tyrosine kinase inhibitor of bcl-abl (CML) and c-kit (GI stromal tumors) Toxicity = fluid retention
64
Rituximab
Monoclonal antibody against CD20 (B cell neoplasms) | Toxicity = increased risk of progressive multifocal leukoencephalopathy
65
Vemurafenib | "VemuRAFenib"
Small molecule inhibitor of forms of B-Raf kinase with V600E mutation Tx metastatic melanoma
66
Bevacizumab
Monoclonal AB against VEGF = inhibits angiogenesis | Toxicity = hemorrhage and impaired wound healing

USMLE Pharmacology (15 decks)

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