Heme + Onc

Question 1

Basophilic stippling

Answer 1

• Lead poisoning​
• Anemia of chronic disease
• alcohol abuse
• Thalassemias

Question 2

1. HbA
2. HbA2
3. HbF
4. HbH
5. HbBarts
6. HbS
7. HbC

Answer 2

1. HbA = alpha2beta2
2. HbA2 = alpha2delta2
3. HbF= alpha2gamma2
4. HbH = beta4 (alpha thalassemia - 3 genes deleted)
5. HbBarts = gamma4 (alpha thal - 4 genes deleted) –> hydrops fatalis
6. HbS (pt mutation in beta: glu–> val)
7. HbC (pt mutation in beta: glu –> lysine)

Question 3

target cells

Answer 3

• HALT said the hunter to his target
• HbC
• Asplenia
• Liver disease
• Thalassemia

Question 4

Heme synthesis

Answer 4

• glycine + succinyl CoA –> delta-aminolevulinic acid (via d-ALA synthase =rate limiting step)
• ALA –> porphobilinogen (dALA dehydratase – lead poisoning)
• Porphorobilinogen deaminase = Acute intermittent porphyria
  
  • tx with glucose and heme (inhibits ALA synthase)
• Uroporphyrinogen decarboxylase = Porphyria cutanea tarda
• protoporphyrin –> heme (ferrochelatase = lead poisoning)

Question 5

1. Bernard-Soulier syndrome
2. Glanzmann thrombasthenia

Answer 5

1. deficient Gp1b – defect in platelet to vWF adhesion (Big Suckers = large platelets)
2. deficient Gp2b/3a –> defect in platelet-platelet aggregation

Question 6

1. ITP
2. TTP

Answer 6

1. anti-Gp2b/3a antibodies
2. deficiency of ADAMTS13 (vWF MMP) –> larger vWF multimers –> platelet aggregation and thrombosis
   
   • neuro symptoms and fever

Question 7

Heparin

Answer 7

• cofactor for antithrombin (which inhibits IIa)
• used during pregnancy, IV only
• protamine sulfate for rapid reversal
• monitor PTT
• LMWH (enoxoparin, dalteparin) act more on factor Xa, are SQ and don’t require constant monitoring
• HIT: development of IgG vs hep-bound PF4

Question 8

Argatroban + bivalrudin

Answer 8

• derivates of anticoag used by leeches
• inhibit thrombin directly – use instead of hep for HIT

Question 9

Warfarin

Answer 9

• coumadin: interferes with gamma-carboxylation of Vit-K dependent clotting factors (II, VII, IX, X) + proteins C and S
• extrinsic pway (increased PT)
• chronic anticoag + oral (unlike hep) – but slower onset
• CI in pregnancy
• tissue necrosis
• reversal: Vit K and FFP

Question 10

Apixaban + rivaroxaban

Answer 10

• directly inhibit factor Xa (X for X)
• tx and prophylaxis of DVT, PE, stroke, Afib

Question 11

thrombolytics

Answer 11

• streptokinase, alteplase (tPA), reteplase (rPA)
• convert plasminogen –> plasmin (cleaves thrombin and fibrin clots)
• Rx: early MI or stroke, direct thrombolysis of PE
• tx toxicity with aminocaproic acid

Question 12

Clopidogrel + Ticlopidine, Prasugrel + ticagrelor

Answer 12

• block platelet ADP receptor – prevents ADP-induced expression of Gp2b/3a
• “clop” and “grel”

Question 13

Gp2b/3a inhibitors

Answer 13

• Abciximab (2x3 = cix)
• eptifibatide + tirofiban (“fib” for fibrin)

Question 14

Methotrexate (MTX)

Answer 14

• folic acid analog
• inhibits DHFR (prevents DHF converted back to THF)
• decreases DNA and protein synthesis
• also used for ectopic pregnancy and RA, psoriasis, IBD
  
  • teratogenic (NTD)
• myelosuppression reversible with leucovorin “rescue”

Question 15

5-fluoruracil (5-FU)

Answer 15

• pyrimidine analog
• inhibits thymdilate synthetase –> decreased DNA + protein synthesis
• rescue with thymidine/uridine

Question 16

Cytarabine

Answer 16

• Pyrimidine analog –> inhibition of DNA polymerase

Question 17

Azithioprine, 6MP and 6TG

Answer 17

• purine analogs – inhibit PRPP synthetase
• decrease purine synthesis
• also used for prevent organ rejection, RA and SLE
• azithioprine and 6MP are metabolized by XO –> increased toxicity with allopurinol

Question 18

Dactinomycin

Answer 18

• intercalates in DNA (antitumor antibiotic)
• Wilms tumor, Ewing sarcoma, rhabdomyosarcoma (childhood tumors)
  
  • kids ACT out

Question 19

Doxorubicin and daunorubicin

Answer 19

• intercalates in DNA –> breaks in DNA
• generates free radicals
• antitumor antibiotic
• cardiotoxic (dilated cardiomyopathy)

Question 20

Bleomycin

Answer 20

• antitumor antibiotic
• induces free radical formation
• Testicular cancer (B for balls)
• pulmonary fibrosis

Question 21

cyclophosphamide

Answer 21

• alkylating agent
• hemorrhagic cystitis (partially prevented with mesna)

*phospho is kind of like alkylating

Question 22

Nitrosureas

Answer 22

• alkylating agents: Carmustine, Lomustine, semustine)
• crosses BBB –> tx brain tumors
• CNS toxicity

“nitro” is like alkylating

Question 23

Busuflan

Answer 23

• alkylating agent
• pulmonary fibrosis (just like the other B- Bleomycin)

“sulf” is like alkylating

Question 24

Vincristine and vinblastine

Answer 24

• prevent polymerization of MTs
• Vincristine = peripheral neuritis
• Vinblastine = BM suppression (“blasts” bone)

Question 25

Paclitaxel and other taxols

Answer 25

• prevent MT depolymerization (mitotic spindle can’t break down) – inhibits cell division
  *

Question 26

cisplatin and carboplatin

Answer 26

• cross-link DNA (via platinum molecule)
• GU association: tx testicular, bladder and ovarian carcinomas
  
  • nephrotoxic
• otoxicity

Question 27

Etoposide and teniposide

Answer 27

• inhibit topoisomerase II –> prevents transcription
• testicular cancer (Eradicate Ball Cancer)

Question 28

hydroxyurea

Answer 28

• inhibits ribonucleotide reductase –> decrease DNA synthesis
• also used to tx SCD (increase HbF)

Question 29

Prednisone

Answer 29

• triggers apoptosis
• Cushing-like symptoms, muscle breakdown, cataracts, acne, osteoporosis, HTN, peptic ulcers, psychosis, hyperglycemia

Question 30

Tamoxifen and Raloxifene

Answer 30

• SERM (E antag in breast and agonist in bone)
• ER+ breast cancer, prevent osteoporosis
• tamoxifen = increased risk of endometrial cancer

Question 31

Trastuzumab (herceptin)

Answer 31

• mAb against HER-2 (c-erbB2) tyrosine kinase receptor
• HER-2 + breast cancer
• cardiotoxic (Heartceptin damages the heart)

Question 32

1. Imatinib
2. Rituximab

Answer 32

1. tyrosine kinase in ihibitor of bcr-abl (CML) and c-kit
2. mAb against CD20 (B cell neoplasms)