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Step 1 Miscellanous > Hematology and Antineoplastics SketchyPharm > Flashcards

Hematology and Antineoplastics SketchyPharm Flashcards

1
Q

What is the mechanism of heparin interfering with potassium balance?

A

Heparin is directly toxic to adrenal cells of the zona glomerulosa -> leads to Type IV RTA (hyperkalemic hypoaldosteronism)

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2
Q

What are the three primary indications for heparin and its reversal agent?

A
  1. Acute PE
  2. DVT
  3. Acute MI

Reversal via protamine sulfate -> does not work as well on LMWH (i.e. enoxaparin, dalteparin)

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3
Q

How are the pharmacokinetics of LMWH different from UFH?

A

LMWH is more bioavailable, longer half life, and eliminated renally (tapering flag sticking into kidney from LMWH daughter)
-> UFH safer in renal insufficiency (metabolized via liver)

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4
Q

What monitoring is required for UFH and LMWH?

A

UFH - aPTT, much more sensitive to changes in factor II levels

LMWH - blood monitoring not required, but this also makes it harder to work with in the acute setting (anti-Xa only assays are only readily available)

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5
Q

What drugs should be immediately thought of for the treatment of HIT after discontinuing the offending agent? What can be used for reversal of these agents if anticoagulation is too much?

A

Direct thrombin inhibitors, i.e. bivalirudin, argatroban, dabigatran

Dabigatran has a reversal agent monoclonal antibody, but the other two you must stop the bleeding somehow:

  1. Anti-tPA’s / antifibrinolytics: tranexamic acid, aminocaproic acid
  2. Prothrombin complex concentrate
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6
Q

What is the main indication for factor Xa inhibitors and what are they?

A

ApiXaban, rivaroXaban

  • > used as direct oral anticoagulants (DOACs) for longterm DVT and PE prophylaxis, as well as stroke prevention in AFib
  • > the only direct thrombin inhibitor which is a DOAC is the one with a reversal agent: Dabigatran.
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7
Q

What factor which procoagulant warfarin inhibits has the shortest halflife? Why is this clinically relevant?

A

Factor 7 - think of the 7 deadly sins soldier on the ground

Relevant because factor 7 is part of the extrinsic pathway

  • > reason why we measure to PT to monitor warfarin activity
  • > rest of factors are part of common pathway (or factor 9).
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8
Q

What drugs notoriously increase and decrease INR with Warfarin? What’s the target INR?

A

Target INR: 2-3

Increase:
TMP-SMX (displaces warfarin from albumin)
All CYP inhibitors, i.e. amiodarone, azithromycin, fluconazole

Decrease: CYP inducers - carbamazepine, phenobarbital, rifampin

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9
Q

What are the fetal abnormalities which result from warfarin use in pregnancy?

A
  1. Bone abnormalities - interferes with gamma-carboxylation needed for calcium-using proteins
  2. Bleeding abnormalities and retinal hemorrhage.
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10
Q

What are the indications for warfarin?

A

Longterm anticoagulation in AFib, or PE / DVT prophylaxis in those at high risk or following the event

  • > think of the ship going down the iliofemoral river
  • > warfarin is generally first line over the expensive Xa inhibitors
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11
Q

What is the mechanism of action of ticagrelor and prasugrel?

A

Same as clopidogrel - block P2Y12 receptor to prevent ADP binding, which prevents upregulation of Gp2b/3a receptors
-> remember that ADP functions to aggregate da platelets

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12
Q

What is dual antiplatelet therapy and what are three indications?

A

Aspirin (anti-TXA2) and ADP receptor blocker (i.e. clopidogrel)

  1. Acute coronary syndromes - broken heart strings
  2. Prevention of coronary stent thrombosis - think of Sammy Sosa corked bats
  3. Ischemic stroke - think of black paint on painter’s head, also seen in statins sketchy
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13
Q

What is the mechanism of action of ticlodipine and the adverse effect of worry?

A

Think Ty Cobb next to the grill

ADP receptor blocker, associated with neutropenia / granulocytopenia (think of the hourglass)

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14
Q

Give three Gp2b/3a inhibitors and their major unique side effect? Indication?

A

Abciximab - monoclonal antibody
Eptifibatide - Tied
Tirofiban - Tied

Side effect - think of broken plates all around -> thrombocytopenia

Main indication - patients about to undergo percutaneous coronary intervention (PCI)

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15
Q

What are the two phosphodiesterase inhibitors used to impair platelet activation and their mechanism of action?

A

Dipyridamole - Two pyramids on tent
Cilostazole - He lost the ball!

increased cAMP will impair platelet aggregation (i.e. TXA2 is meant to decrease cAMP synthesis), also causes vasodilation

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16
Q

What is the main indication for dipyridamole?

A

Sometimes used in combination with aspirin for the prevention of stroke (dual therapy)

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17
Q

What is cilastazol used for?

A
  1. Coronary steal testing -> causes general coronary vasodilation
  2. Can be used for intermittent claudication -> prevents pain from peripheral artery disease by direct arterial vasodilation
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18
Q

When but thrombolytics be administered for ischemic stroke? When should it be administered for MI? Also give a list of these drugs in your answer.

A

Streptokinase, alteplase, reteplase, or tenecteplase must be administered within 3-4.5 hours of stroke onset

Administer for MI if patient cannot have percutaneous coronary intervention within two hours (think of the guy in the background holding up two fingers)

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19
Q

What are some contraindications of fibrinolytic therapy?

A
  1. Recent head trauma
  2. Recent neurosurgery
  3. Active bleeding
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20
Q

What can be used for reversal of thrombolytic therapy?

A

Competitive inhibitors of plasminogen - tranexamic acid (exam) or aminocaproic acid (capping paint)

FFP - fighter plane
Crypoprecipitate - the cap that the kid is wearing

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21
Q

What are the gynecologic uses of methotrexate?

A

Think of the uterus backpack with shit falling out

  1. Abortion - in combination with misoprostol
  2. Molar pregnancy / choriocarcinoma - think of the mole falling out of the bag
  3. Unruptured ectopic pregnancy - think of the baby hanging from the straps
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22
Q

What are the uses of methotrexate in treatment of chronic inflammatory conditions?

A

Psoriasis - think of the scaly pads
Rheumatoid arthritis - think of the lanterns
IBD, SLE, vasculitis, dermatomyositis (after steroids) - other inflammatory conditions

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23
Q

What are the main side effects of MTX? Are any of these acutely reversible?

A

Myelosuppression - reversible by leucovorin / folinic acid
Pulmonary fibrosis - progressive, think bonzai tree
Hepatotoxicity - sweat spot on Chef - monitor LFTs
Oral mucositis - poking your mouth
Alopecia

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24
Q

When 5-fluorouracil is given, what is the product which actually interferes with thymidine synthesis? Why is this relevant?

A

5-FU is made into 5-fluorodeoxyuridinemonophosphate (5-FdUMP) sits in the active site of thymidylate synthetase along with reduced folate.

If MTX is given along with 5-FU, it can actually inhibit 5-FU’s action by limiting reduced folate’s availability
-> effects are actually enhanced by leucovorin

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25
Q

What is FU used to treat? Why?

A

Treats solid tumors with long-term low dosages, since leukemias often lack the salvage pathways required to activate it (not useful for these)

Especially good for colorectal cancer, pancreatic cancer, and basal cell carcinoma.

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26
Q

What does high vs low-dose FU do in terms of toxicity?

A

High dose: myelosuppresion

Low dose: dose used for solid tumors - simply pain and swelling of palms and soles of feet “hand foot syndrome”, also called “erythrodysthesia”

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27
Q

What is the function of ribonucleotide reductase? What inhibits them?

A

Converts ribonucleotides to deoxyribonucleotides

Inhibited by hydroxyurea

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28
Q

What is the mechanism of action of 6-MP and what is the name of its prodrug? What must activate it?

A

Azathioprine - 6-mercaptopurine

Activated by HGPRT (think of HiGh PRiesT)

Inhibits formation of IMP (think of azameralda kicking over the IMP imp) -> stops de novo purine synthesis

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29
Q

What is the drug interaction of note with azathioprine?

A

Inhibitors of xanthine oxidase (i.e. febuxostat, allopurinol) will slow the degradation of 6-MP

  • > more 6-MP will go through the HGPRT pathway
  • > toxic accumulation and bone marrow suppresion
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30
Q

What are the side effects of 6-MP?

A

Myelosuppression (nun holding birdseed marrow)
Liver toxicity (liver apron)
Pancreatitis (pancreas sponge)

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31
Q

What are the indications for 6-MP?

A

Hematologic malignancies - T and B cell, stained glass
RA, SLE - similar to MTX
Think IBD including ulcerative colitis / Crohn’s with the inflamed haustra lanterns

32
Q

What is the mechanism of action of mycophenolate mofetil? Indications?

A

IMP dehydrogenase inhibitor -> needed for making of GMP

  • > used for lupus nephritis primarily
  • > also inhibits inflammatory cell production which may be useful in RA, MG, and graft rejection
33
Q

Side effects of mycophenolate?

A

Myelosuppression, GI upset, invasive CMV infections secondary to myelosuppression

34
Q

What is the first line treatment for hairy cell leukemia and its mechanism of action?

A

Cladribine - think of Hairy caveman “clad” in bearskins

  • > holding a purine stick
  • > adenosine analog inhibiting DNA polymerase

Used with purine analog pentostatin with a similar mechanism

35
Q

What is the prodrug of 5-FU called and what is needed before it can work?

A

Capecitabine - 5-FU prodrug

Think of that saber-tooth tiger wearing a CAPE and you’ll remember CAPEcitabine is the prodrug of 5-FU (gotta hallucinate to think of this).

All pyrimidine analogs need to be phosphorylated before they can be used to inhibit DNA/RNA enzymes

36
Q

Give two other pyrimidine analogs other than 5-fluorouracil. What is their mechanism?

A
  1. Cytarabine - Saber toothed tiger with hexagon spots
  2. Gemcitabine - bags of gems around the tiger

Rather than inhibiting thymidylate synthase (they are not uracil-like), they are phosphorylated in the cells and become inhibitors of DNA synthesis in the S phase.

37
Q

What is the difference in indication between cytarabine and gemcitabine?

A

Cytarabine - think of the archers in the cave next to the saber tooth tiger - only good for hematologic malignancies

Gemcitabine - think of the crabs on the gem rocks -> also decent against solid malignancies

38
Q

What is cyclophosphamide a derivative of, and how does it actually work? Is it specific to a phase of the cell cycle?

A

Nitrogen mustard

Works by liver activation (CYP450 chariot) into alkylating products, which can be used to induce immune suppression as a broad spectrum agent -> cell cycle nonspecific

Attaches alkyl groups to N-7 nitrogen of guanine

39
Q

What renal side effect is cyclophosphamide known for (NOT bladder side effect)?

A

SIADH -> think of the bucket on the cyclops’ head

This is also caused by carbamazepine.

40
Q

What is the mechanism and usage of busulfan?

A

Cross-links DNA. It’s another alkylating agent - think Beautiful Sirens

Used to ablate a patient’s bone marrow before bone marrow transplantation

41
Q

What are the adverse effects of busulfan?

A

“Busulfan tan” - hyperpigmentation of skin - also think about how the sirens’ skin was brown

Pulmonary fibrosis - lung tree on their chest

Severe myelosuppression - bones all around them. But this should be obvious because that’s the point of the drug.

42
Q

What drugs are the nitrosureas?

A

Think of the nitrosurea centaurs.

Horse legs = mustang
-> carmustine, lomustine

Zebra stripes = Streptozocin

43
Q

What are the nitrosureas good for and what must happen before they can work?

A

Require bioactivation in the liver

They can cross the blood-brain barrier and act in the CNS

  • > used for the treatment of glioblastoma multiforme
  • > obviously will cause major CNS toxicity
44
Q

What is the mechanism of action of cisplatin / carboplatin and its use?

A

Crosslinks DNA - except with platinum

Used against solid tumors like testicular / ovarian cancer, as well as lung cancers

45
Q

What are the side effects of cisplatin / carboplatin / oxaliplatin?

A

Ototoxicity - think of gong earrings
Nephrotoxicity - acute kidney injury and Fanconi syndrome - kidney bag
Peripheral neuropathy - think of stocking and gloves on lady

46
Q

Which platinum antineoplastics are most likely to cause renal toxicity and how is this combated? Why does this happen?

A

Cisplatin - most likely
Oxaliplatin - least likely

Can cause ATN - muddy brown drain gutter next to the store. Due to generation of free radicals.

Amifostine (amethyst crystal in sketchy) can be used to prevent toxicity to renal tubule via scavenging free radicals. Also, giving IV saline (think of the guy spraying the window) induces diuresis and prevents ATN.

47
Q

What part of bleomycin’s side effect profile makes it very useful compared to other chemotherapeutic agents? What part of the cell cycle is it specific for and what is its mechanism?

A

Breaks and fragments DNA strands via free radicals, keeps cells locked in G2 phase.

Useful because it is detoxified by most tissues except lung and skin (no marrow toxicity)

48
Q

What are the toxicities of concern for bleomycin?

A

Fibrosis of lung - lung coral
Dermatitis of skin, with hyperpigmentation - hyperpigmented stripes

(related to lack of detoxification in lung and skin)

49
Q

What drugs are the anthracyclines and how do they work?

A

Doxorubicin and daunorubicin
-rubicin rubies with Santa Anthracyclin

Work by generating free radicals (bubbles) and intercalating in DNA (rubies in seaweed) -> reduction in DNA replication

50
Q

What are the toxicities of the anthracyclines? How can it be prevented?

A

Dose-dependent cardiac toxicity (dilated cardiomyopathy) due to mitochondrial damage via free radicals

Prevent with dexrazoxane (skeleton raising the razor on deck) - iron chelating agent

51
Q

How does actinomycin D work?

A

Intercalating agent (think of the artifacts in the seaweed DNA)

52
Q

What are the indications for actinomycin D?

A

Think of the actinomycin Doll -> childhood malignancies

Especially effective against Wilms tumor, Ewing sarcoma, and rhabdomyosarcoma

53
Q

Name the Topoisomerase I and Topoisomerase II inhibitors? What is the mechanistic difference between these two?

A

Topoisomerase II induces two breaks while Topo I only induces one.

Topoisomerase I inhibitors - Irinotecan, topotecan

Topoisomerase II inhibitors - Etoposide, teniposide

54
Q

What are the indications for topoisomerase II inhibitors?

A

Solid tumors, especially testicular and small cell lung cancer, as well as leukemias / lymphomas
-> relatively rapidly dividing cells

55
Q

What are the indications for the topoisomerase I inhibitor and the main toxicity of interest?

A

Irinotecan - Colon cancer
Topotecan - Ovarian and small cell lung cancers

Severe diarrhea -> think of the bird pooping on the hand of the prince

Obviously they all cause myelosuppression and alopecia

56
Q

What is the mechanism of vincristine / vinblastine and how does it differ from the taxols? What part of the cell cycle do they work in?

A

Vincristine / vinblastine - bind B-tubulin and prevent microtubule polymerization

Taxols, i.e. paclitaxel - Hyperstabilize microtubules so they cannot be broken down

Both are M-phase specific toxins

57
Q

What are the side effects of Vincristine?

A

Neurotoxicity - peripheral neuropathy -> stocking and gloves

Constipation - monkey holding plunger - paralytic ileus

58
Q

What are the side effects of vinblastine and paclitaxel?

A

Both severe bone marrow suppression (think of blasted bones)

Paclitaxel specific - holding Christine’s glove - neuropathy

59
Q

What does -tinib vs -nib mean?

A
  • nib = kinase inhibitor
  • ti = tyrosine
  • tinib = tyrosine kinase inhibitor

vemurafenib = BRAF kinase inhibitor. Still ends in -nib because kinase inhibitor, but not tinib.

60
Q

What is one indication for imatinib other than CML and what is its main side effect?

A

c-KIT mutations - gastrointestinal stromal tumors

Side effect - peripheral / periorbital edema

61
Q

What cancer type is erlotinib used for?

A

EGFR-mutated non-small cell lung cancers (that lung lapel isn’t small at all!)

Remember the GEOFFREY cap he’s wearing to remember EGFR

62
Q

What are the toxicities of erlotinib?

A

Rash (think of the Earl’s rash on his face)

Diarrhea (think of his soiled pants)

63
Q

What drugs are VEGF tyrosine kinase inhibitor? What type of cancer does they primarily treat?

A

Sunitinib (sun outside the building with VEGF vegetables in the field)
Sorafenib - misnomer, but just think of the soaring eagle. Also acts on VEGF.

Treats renal cell carcinoma (flank crab buckles on farmer)

64
Q

What are the common toxicities of sunitinib?

A

Hyperkeratosis / rash - out in the hot sun
Hypertension (like bevacizumab) - due to inhibition of VEGF. This is more high yield than sketchy’s hemorrhage side effect.

65
Q

How is vemurafenib a mnemonic for what it actually does?

A 
Vemurafenib
Ve = V600E
Mu = Mutated
Raf = BRAF
Nib = tyrosine kinase inhibitor
66
Q

What is the target antigen of rituximab and what is one infection which may occur with its use? Its most common side effect?

A

Anti-CD20

Associated with PML (think of the crown)

Antibody reacting with lymphocytes -> infusion reaction with hypotension, hives, fever, etc

67
Q

What side effect is thought to occur most commonly with chimeric antibodies (i.e. rituximab, cetuximab)?

A

Serum sickness -> 7-10 days later, a type 3 hypersensitivity with arthralgias, fever, and rash due to deposition of immune complexes formed when we make antibodies vs the chimeric antigens in the monoclonal antibodies.
-> think of the guy with the crown dropping his cup

68
Q

What is the mechanism of action of cetuximab and what cancers is it useful for?

A

EGFR tyrosine kinase inhibitor - Giraffe

Colorectal cancer
-> when KRAS is normal/wild type, so the cancer is being driven by overexpression of EGFR (does not work in mutated KRAS)

Also works in head and neck squamous cell cancers

69
Q

What are the side effects of cetuximab?

A

Rash - similar to Erlotinib (due to activity against EGFR in skin)

Infusion reactions and serum sickness can occur, as would be expected

70
Q

What drug is the prototypical VEGF monoclonal antibody and how does it work?

A

Bevacizumab - the beverage lady

Works by binding the VEGF ligands to prevent downstream signalling and impede angiogenesis to tumors

71
Q

What cancers is bevacizumab useful against? Adverse effects?

A

Useful against renal cell cancer (like sunitinib and sorafenib)

Also colorectal cancer

Adverse effects -

72
Q

What is another indication for bevacizumab that isn’t cancer? What other drug is similar?

A

Along with ranibizumab, these VEGF inhibitors can be used to treat wet macular degeneration, which is a condition caused by hypoxia inducing VEGF new vessel production -> retinal damage

73
Q

What are the potential adverse effects of bevacizumab?

A
  1. Bleeding (blood on beverage lady’s shirt)
  2. GI perforation - think of tube rupturing below
  3. Blood clots - increased risk for venous thrombosis and strokes - think of cubes clogging up the beverages
  4. Hypertension (increases peripheral vascular resistance)
  5. Impaired wound healing (lack of bloodflow)
74
Q

What is the mechanism of action of Alemtuzumab and when is it used?

A

Think of “alms” - CD52 inhibitor -> intertwined 5’s and 2’s on that guy’s sword, found on T and B lymphocytes
-> used for the treatment of CLL (think of the chronically worn tapestry above)

75
Q

What is the important EGFR2 antibody and what are its mechanisms?

A

Trastuzumab - Think of tapestry

Activity against HER2 receptor -> think of her two kids in the tyrosine kinase wheel

Also has ADCC activity - antibody-directed cell-mediated cytotoxicity

76
Q

What is the unique toxicity of trastuzumab? What is one cancer other than breast which it can be used to treat?

A

Cardiotoxicity - think of hearts hanging from her tapestry
-> reversible with discontinuation

Can treat gastric cancer

77
Q

What is the ideal anticoagulant treatment for women, given pregnancy is a hypercoagulable state?

A

LMWH’s - which require minimal routine laboratory monitoring and have a long halflife

Switch to UFH at term -> shorter halflife, can be stopped rapidly at labor to prevent hemorrhage

Direct thrombin inhibitors and Xa inhibitors are CONTRAINDICATED due to pregnancy risk #1194

Step 1 Miscellanous (40 decks)

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