Final Exam Flashcards

Question

Types of Metabolic Alkalosis

Answer 1

Saline Responsive (urinary Cl < 10-20 mEq/L) Saline Resistant (urinary Cl > 20 mEq/L)

Answer 2

- diuretics - vomiting/NG suction - exogenous HCO3- administration or blood transfusions

Answer 3

- increased mineralocorticoid activity - hypokalemia - renal tubular chloride wasting (Bartter's Syndrome)

Answer 4

Saline Responsive: - 1st line: NS +/- potassium supplement - Other: CA-I, HCl acid Saline Resistant: - decrease the dose of mineralocorticoid or change the agent - potassium supplement or potassium-sparing diuretic (spironolactone) - fluids

Answer 5

- airway obstruction --> foreign body, asthma, aspiration - decreased stimulation from CNS --> trauma, CNS infection, overdose, sleep apnea - cardiopulmonary decline --> cardiac arrest, PE - neuromuscular defects --> ALS, Gillian-barre - mechanical ventilation

Answer 6

mechanical ventilation + O2 - caution O2 in COPD

Answer 7

- central stimulation --> anxiety, pain, trauma, injury - peripheral stimulation --> hypoxia, hypotension, CHF - pulmonary edema, PE, pneumonia - salicylate toxicity - mechanical ventilation

Answer 8

mechanical ventilation + sedation +/- NMBA

Answer 9

1) Altered drug metabolism - increased efflux transporters (PgP, MRP) - decreased influx transporters and membrane permeability - decrease activation of prodrug - increased detoxification via CYP450 2) Changes in drug target/function - increased expression of drug target through gene amplification - emergence of mutant target - cells rewire pathway to bypass the need for drug target 3) Physiological changes - refuge of cancer cells in drug-protected sites (BBB) - massive stromalization to decrease penetration - change of state

Answer 10

Pregnenolone --> 17 alpha hydroxylase --> 17 alpha hydroxy pregnenolone 17 alpha hydroxy pregnenolone --> 17,20 lyase --> DHEA Testosterone --> 5 alpha reductase --> DHT Testosterone --> Aromatase (CYP19) --> Estradiol Androstenedione --> Aromatase (CYP19) --> Estrone

Answer 11

- pediatric acute lymphoblastic leukemia - multiple myeloma - lymphomas

Answer 12

Exemestane - MOA: structurally similar to androstenedione acting as a false substrate that aromatase converts to reactive intermediate that irreversibly inhibits at the active site - Treatment: breast cancer in postmenopausal - Side effects: * hot flashes * peripheral edema and weight gain * increased cholesterol levels

Answer 13

- 30% of acute myeloid leukemia What? FLT3 ligand is a cytokine receptor important for hematopoietic cell survival Types of Mutations - internal tandem duplication (ITD): increased dimerization of kinase Types of Inhibitors - 1st gen: broad - 2nd gen: specific - type 2: ITD

Answer 14

- 95% of chronic myeloid leukemia - formed by joining the 5' portion of the Bcr gene (chromosome 22) with the 3' portion of the Abl gene (chromosome 9) forming a chimeric Bcr-Abl

Answer 15

- ALK is normally a transmembrane receptor tyrosine kinase - when ALK becomes inappropriately fused to ELM4, it becomes cytoplasmic and constitutively active

Answer 16

- BRAF V600 activates downstream MEK and ERK pathways leading to increased cell proliferation and survival

Answer 17

- BTK is important in normal B cell activity and tumor growth

Answer 18

- MOA: electrophile intermediate alkylates nucleophile preventing DNA replication & transcription via cross-links - Strategy to reduce reactivity & increase selectivity? --> decreasing nucleophilicity of nitrogen by adding aryl groups ** pulls the electron density from the nitrogen through resonance to decrease how reactive the electrophile is - Side effects: ** myelosuppression ** N/V/D ** secondary malignancy - Resistance ** increase concentration of glutathione ** increase expression of glutathione S-transferase ** upregulate DNA repair enzymes

Answer 19

- MOA: electrophile intermediate alkylates nucleophile preventing DNA replication & transcription via cross-links - Strategy to reduce reactivity & increase selectivity? --> prodrug strategy ** cyclophosphamide --> phosphoramide mustard + acrolein ** phosphoramide mustard is the active metabolite that cross-links the DNA --> highly polar and short t1/2 life ** phosphoramide mustard is inactivated by aldehyde dehydrogenase (ALDH) --> high levels of ALDH in bone marrow reduce myelosuppression ** acrolein accumulates in the urine causing bladder mucosa damage --> MESNA is the treatment - Side effects: ** minimal myelosuppression ** hemorrhagic cystitis - Resistance: ** increase concentration of glutathione ** increase expression of glutathione S-transferase ** upregulate DNA repair enzymes

Answer 20

- MOA: electrophile intermediate alkylates nucleophile preventing DNA replication & transcription via cross-links --> BIFUNCTIONAL CROSS-LINKS - Side effects: ** myelosuppression - Resistance: ** increase concentration of glutathione ** increase expression of glutathione S-transferase ** upregulate DNA repair enzymes

Answer 21

- MOA: requires reverse hydrolysis in aqueous solution ** equilibrium favors cisplatin in plasma with high Cl- concentrations ** equilibrium favors aquo form inside the cell with low Cl- concentrations ** aquo form is the electrophile that reacts with nucleophiles on DNA base pairs to form a INTRASTRAND cross-link by binding at the guanine N7 and adenine N7 sites - Side effects: ** nephrotoxicity ** peripheral neuropathy ** ototoxicity ** N/V ** minimal myelosuppression - Resistance: ** increase concentration of glutathione ** increase expression of glutathione S-transferase ** upregulate DNA repair enzymes

Answer 22

- MOA: binds to Topo I through intercalation and forms a ternary complex that blocks DNA relegation - Cell Cycle: S-phase - Drug Interaction: UGT1A1 ** causes toxicity from SN-38 accumulation - Resistance: ** increased expression of glutathione S-transferase ** increased PgP and MRP efflux transporters

Answer 23

- MOA: binds to Topo II through intercalation and blocks DNA relegation AND produces free radicals - Cell Cycle: non cell cycle specific - Toxicity: Cardiotoxicity ** EDTA can chelate iron-catalyzed free radical formation through Dexrazoxane ** local tissue damage via extravasation - Resistance: ** increased expression of glutathione S-transferase ** increased PgP and MRP efflux transporters

Answer 24

- MOA: binds to Topo II and blocks DNA relegation NO INTERCALATION NOT SENSITIVE TO GLUTATHIONE - Cell Cycle: G2 phase - Resistance: ** increased PgP and MRP efflux transporters

Answer 25

- MOA: thiazole intercalates DNA and imidazole produces free radicals leading to single-strand and double-stranded DNA breaks - Cycle Cycle: G2/M phase - Toxicity: Pulmonary toxicity ** enzyme that inactivates is low in skin and lungs

Answer 26

- MOA: binds to tubulin to inhibit microtubule assembly (polymerization) --> mitotic arrest - Toxicity: ** peripheral neuropathy ** local tissue damage via extravasation - Resistance: ** increased PgP or MRP efflux transporters

Answer 27

- MOA: binds to the end of microtubules & prevents elongation LOWER RATE OF NEUROTOXICITY - Resistance: ** increased Pgp & MRP efflux transporters

Answer 28

-MOA: 1) promotes assembly of a stable bundle that decreases free tubulin 2) stabilization blocks depolymerization & segregation - Toxicity: ** myelosuppression ** some peripheral neuropathy - Resistance: **increased PgP & MRP efflux transporters

Answer 29

- MOA: 1) promotes assembly of a stable bundle that decreases free tubulin 2) stabilization blocks depolymerization & segregation - Toxicity: ** myelosuppression ** some peripheral neuropathy NOT A PgP SUBSTRATE

Answer 30

- MOA: * Normal: in the presence of tetrahydrofolate, dUMP binds to the active site of thymidylate synthase forming a ternary complex to allow for an exchange of H+ for methyl-creating TMP * 5-FU: in the presence of tetrahydrofolate, FdUMP binds to the active site of thymidylate synthase forming a ternary complex that cannot allow fluorine to exchange for methyl-stopping TMP production - Drug Rescue: thymidine - Drug Synergy: leucovorin --> stable cofactor converted to tetrahydrofolate inside cells - Resistance: ** upregulate thymidylate synthase ** downregulate enzyme that converts 5-FU to FdUMP - Toxicity: ** polymorphism in dihydropyridine dehydrogenase that metabolizes 5-FU

Answer 31

- MOA: converted to Ara-CTP intracellularly where it competitively inhibits DNA polymerase and incorporates into DNA to further inhibition - Pearl: cytidine deaminase converts Ara-CTP into non-toxic uracil arabinoside ** low levels of cytidine deaminase in CNS --> highly toxic - Drug Synergy: tetrahydrouridine --> cytidine deaminase inhibitor - Resistance: ** upregulate cytidine deaminase ** downregulate activating enzymes ** downregulate drug importers

Answer 32

- MOA: inhibits multiple enzymes in the purine biosynthesis pathway - Resistance: loss of HGPRT activating enzyme - Drug Interaction: ** TPMT ** allopurinol

Answer 33

- MOA: * Normal: FH2 enters the folate pool where it's reduced by dihydrofolate reductase into FH4 (tetrahydrofolate) * MTX: inhibits dihydrofolate reductase inhibiting TMP synthesis - Drug Rescue: leucovorin --> stable cofactor converted to tetrahydrofolate inside cells - Resistance: ** upregulate dihydrofolate reductase ** mutation of dihydrofolate reductase ** decrease polyglutamation decreasing MTX accumulation

Answer 34

5-FU: S phase Cytarabine: S phase 6-MP: S phase MTX: S phase Chlorambucil: cell cycle non-specific Cyclophosphamide: cell cycle non-specific Mitomycin C: cell cycle non-specific Cisplatin: cell cycle non-specific Irinotecan, Topotecan: S phase Doxorubicin: cell cycle non-specific Etoposide: G2 phase Bleomycin: G2/M phase Vincristine: M phase Eribulin: M phase Paclitaxel: M phase Ixabepilone: M phase

Answer 35

Doxorubicin & Vincristine

Answer 36

Ixabepilone

Answer 37

4.8-10.8 x 10^3

Answer 38

< 0.5 x 10^3

Answer 39

140-440 x 10^3

Answer 40

< 10 x 10^3

Answer 41

4.8-6.2 x 10^12

Answer 42

Hb < 11 g/dL OR > 2 g/dL drop from baseline

Answer 43

- the patient is receiving myelosuppressive chemotherapy with curative intent - the patient is receiving non-myelosuppressive chemotherapy - the patient is not receiving chemotherapy

Answer 44

- Cancer + CKD - the patient is receiving palliative chemotherapy - unknown cause