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USMLE Pharmacology > Hematology > Flashcards

Hematology Flashcards

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USMLE® Step 1 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
Q

How does ASA irreversibly inhibit COX?

A

Covalent acetylation

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26
Q

Aspirin labs

A

Increased bleeding time
Decreased TXA2 and prostaglandins
NORMAL PT/PTT

Affects primary hemostasis

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27
Q

Aspirin overdose acid/base

A

Respiratory ALKALOSIS initially

superimposed metabolic ACIDOSIS later

28
Q

Aspirin toxicity

A

Gastric ulceration
Tinnitus
Chronic use = acute renal failure, interstitial nephritis, upper GI bleed

29
Q

Should you give ASA to a child?

A

NO = can cause Reye syndrome!

30
Q

ADP (P2Y12) receptor inhibitors (5)

A 
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
Q

P2Y12 inhibitor toxicity

A

Neutropenia (ticlopidine)

TTP/HUS may be seen

32
Q

Cilostazol, dipyridamole
MOA?
Toxicity?

A

Phosphodiesterase III inhibitors

Block cAMP –> AMP = increased cAMP in platelets, which inhibits platelet aggregation
Vasodilators

Toxicity = nausea, headache, facial flushing, hypotension, abdominal pain

33
Q

GPIIb/IIIa inhibitors (3)

Toxicity?

A

Abciximab (“six”)
Eptifibatide
Tirofiban

Bind to GPIIb/IIIa on activated platelets and prevent aggregation = prevent fibrinogen cross linking

Toxicity = bleeding, thrombocytopenia

34
Q

Antimetabolites

A

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
Q

Methotrexate

A

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
Q

Methotrexate “rescue”

A

Leucovorin (folinic acid)

37
Q

5-FU

A

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
Q

5-FU “rescue”

A

Uridine

39
Q

Cytarabine

A

Pyrimidine analog
Inhibition of DNA polymerase

Toxicity:
Leukopenia
Thrombocytopenia
Megaloblastic anemia (folate deficiency)
(CYTarabine = panCYTopenia)
40
Q

Azathioprine, 6-MP, 6-TG

A

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
Q

Antitumor antibiotics

A

Dactinomycin (actinomycin D)
Doxorubicin (Adriamycin), daunorubicin
Bleomycin

42
Q

Dactinomycin

A

Intercalates in DNA
Used for childhood tumors
Toxicity = myelosuppression

43
Q

Doxorubicin, daunorubicin

A

Generate free radicals
Intercalate in DNA = breaks = decreased replication

Toxicity = CARDIOTOXICITY (dilated cardiomyopathy), myelosuppression, alopecia

44
Q

Agent used to reduce cardiotoxicity from doxorubicin and daunorubicin

A

Dexrazoxane = iron chelating agent

45
Q

Bleomycin

A

Induces free radical formation = breaks in DNA

Toxicity = PULMONARY FIBROSIS, skin changes, mucositis; minimal myelosuppression

46
Q

Alkylating agents

A

Cyclophosphamide, ifosfamide
Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
Busulfan

47
Q

Enzymes inhibited by lead

A

ALA dehydratase

Ferrochelatase

48
Q

Lead poisoning treatment

A

Dimercaprol and EDTA

Succimer used for chelation for kids

49
Q

Sideroblastic anemia treatment

A

Pyridoxine (B6, cofactor for delta-ALA synthase)

50
Q

Cyclophosphamide, isofosfamide

A

Covalent cross-links DNA at guanine N7
Bioactivation by liver

Toxicity:
Myelosuppression
Hemorrhagic cystitis (prevent with mesna)

51
Q

Agent used to prevent hemorrhagic cystitis due to cyclophosphamide

A

Mesna

Thiol group binds toxic metabolites

52
Q

Nitrosoureas

A

Carmustine, lomustine, semustine, streptozocin
Cross BBB to CNS, cross links DNA
Treatment for brain tumors
Toxicity = CNS; convulsions, dizziness, ataxia

53
Q

Busulfan

A

Cross-links DNA
CML; ablates bone marrow before transplant
Toxicity = myelosuppression, pulmonary fibrosis, hyperpigmentation

54
Q

Vincristine, vinblastine

A

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
Q

Paclitaxel and other taxols

A

Hyperstabilize polymerized microtubules in M phase so spindle cannot break down (prevent anaphase)
INHIBITS DEPOLARIZATION
“Taxing to stay polymerized”
Toxicity = myelosuppression, alopecia, hypersensitivity

56
Q

Cisplatin, carboplatin

A

Non-classical alkylating agents
Cross-link DNA
Nephrotoxicity and acoustic nerve damage
Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis

57
Q

Etoposide, tenoposide

A

Topoisomerase II inhibitors = increase DNA degradation

Myelosuppression, GI irritation, alopecia

58
Q

Irinotecan, topotecan

A

Topoisomerase I inhibitors = prevent DNA unwinding and replication
Severe myelosuppression, diarrhea

59
Q

Hydroxyurea

A

Inhibits ribonucleotide reductase = decreases DNA synthesis (S-phase specific)
Bone marrow suppression, GI upset

60
Q

Prednisone, prednisolone, dexamethasone

A

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
Q

Tamoxifen, Raloxifene

A

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
Q

Trastuzumab

A

Herceptin
Monoclonal AB against HER-2 (c-erbB2) = tyrosine kinase receptor = kills breast cancer cells that overexpress HER-2
Cardiotoxicity = damages the heart

63
Q

Imatinib

A

Gleevec
Tyrosine kinase inhibitor of bcl-abl (CML) and c-kit (GI stromal tumors)
Toxicity = fluid retention

64
Q

Rituximab

A

Monoclonal antibody against CD20 (B cell neoplasms)

Toxicity = increased risk of progressive multifocal leukoencephalopathy

65
Q

Vemurafenib

“VemuRAFenib”

A

Small molecule inhibitor of forms of B-Raf kinase with V600E mutation
Tx metastatic melanoma

66
Q

Bevacizumab

A

Monoclonal AB against VEGF = inhibits angiogenesis

Toxicity = hemorrhage and impaired wound healing

USMLE Pharmacology (15 decks)

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