REVISED 510 Final Exam Review - focusing on blueprint

The ____ the mineralocorticoid potency, the ___ the therapeutic duration

higher, shorter

List the steroid conversions

hydrocortisone 20

prednisone 5

prednisolone 5

methylprednisolone 4

dexamethasone 0.75

Which CYP enzyme are steroids substrates of? Are they inducers or inhibitors?

CYP3A4, inducers

Long term steroids have many side effects. List 3.

Could list: HTN, weight gain, hyperglycemia, fluid retention, hypokalemia, skin thinning, osteoporosis

How can you test if a patient’s HPA axis is suppressed?

cortrosyn stimulation test

Which cytotoxic chemo drug classes are cell cycle specific, and which part of the cell cycle do they target?

antimetabolites - S

topoisomerase inhibitors - S

vincas - M

taxanes - M

Identify the cytotoxic agent by MOA: forms DNA crosslinks with alkyl-N-alkyl

alkylating agents

Identify the cytotoxic agent by MOA: forms DNA crosslinks with a platinum ion

platinum alkylator

Identify the cytotoxic agent by MOA: inhibits DHFR

antimetabolite - folic acid

Identify the cytotoxic agent by MOA: ara-CTP inhibits DNA polymerase to disrupt synthesis

antimetabolite - cytidine

Identify the cytotoxic agent by MOA: FUTP forms ternary complex with thymidylate synthase to inhibit dTMP synthesis

antimetabolite - pyrimidine

Identify the cytotoxic agent by MOA: do not allow unwinding of supercoiled DNA, prevents transcription

topoisomerase inhibitors

Identify the cytotoxic agent by MOA: formation of radicals to break DNA strands

anthracyclines

Identify the cytotoxic agent by MOA: prevent microtubule formation

vincas

Identify the cytotoxic agent by MOA: prevent microtubule disassembly

taxanes

Non specific chemo can be given as a _____ while specific agents are usually given as _____

bolus; CIVI

Add _____ to ifosfamide to prevent urine crystallization due to acrolein

mecna

What equation is used to calculate carboplatin doses

mg = AUC (CrCl + 25)

Fluorouracil given as a bolus most commonly causes ______ whereas given as a CIVI most commonly causes _____

myelosuppression, GI toxicity

Identify the cytotoxic agent by its toxicities: myelosuppression, NV, secondary malignancies, infertility

alkylating agents

Identify the cytotoxic agent by its toxicities: AKI/nephrotoxicity, emetogenesis

cisplatin - platinum alkylator

Identify the cytotoxic agent by its toxicities: neuropathies, delayed hypersensitivity after 6-8 cycles

oxaliplatin - platinum alkylator

Identify the cytotoxic agent by its toxicities: renal/hepatic dysfunction, diarrhea, mucositis, third spacing

methotrexate

Identify the cytotoxic agent by its toxicities: cerebellar toxicity, conjunctivitis

cytidine

Identify the cytotoxic agent by its toxicities: hand-foot-syndrome, GI toxicities

capecitabine

Identify the cytotoxic agent by its toxicities: early or late onset diarrhea

topoisomerase inhibitors

Identify the cytotoxic agent by its toxicities: cardiac toxicity, extravasation, mucositis

anthracyclines

Identify the cytotoxic agent by its toxicities: constipation, neurotoxicity

vincas

Identify the cytotoxic agent by its toxicities: neuropathies, hypersensitivity reactions

taxanes

Which monoclonal antibody agent targets CD20 on B-cells

rituximab

Which monoclonal antibody agent targets VEGF

bevacizumab

What are common adverse effects seen with bevacizumab, a VEGF agent

HTN, clotting disorders, delayed wound healing

Which monoclonal antibody agent targets EGFR

cetuximab

What are common adverse effects of cetuximab, an EGFR agent

rash, diarrhea, hypersensitivity

Which monoclonal antibody agent targets HER2

trastuzumab

What are common adverse effects of trastuzumab, a HER2 agent

LVEF, rash, infusion reactions

Which biomarkers are associated with the use of TKIs

exon 19 and L858R on exon 21

What are common adverse effects of EGFR inhibitors and how should they be managed

rash, diarrhea; loperamide

A mutation in which gene (that is downstream from EGFR) would predict resistance to cetiximab or panitumumab, which are EGFR monoclonal antibodies?

KRAS

List some cytokine-associated toxicities seen in CAR-T therapy

hypotension, fever, hypoxia and neurologic changes

Diarrhea after a couple weeks of an immune checkpoint inhibitor should be treated with ___

steriods

Bactericidal or bacteriostatic? beta lactams, vanc, aminoglycosides, fluoroquinolones, dapto

bactericidal

Bactericidal or bacteriostatic? macrolides, tetracyclines, clindamycin, sulfa, linezolid

bacteriostatic

What is the PD target of amoglycosides

Cmax/MIC

What is the PD target of FQ, vanc, macrolides, doxycyline, linezolid

AUC/MIC

What is the PD target of beta-lactams

T over MIC

Where do tetracyclines exert their MOA

A site of 30s

Where do macrolides and lincosamides exert their MOA

exit tunnel of 50s

Where do oxazolidinones exert their MOA

23s portion of 50s

Where do aminoglycosides exert their MOA

30s, causing mRNA misreading

Which ribosomal agent is good for intracellular pathogens and highly tissue perfused

tetracyclines

Which ribosomal agent distributes into macrophages and reaches high intracellular concentrations to exert a long half life

azithromycin

Match the adverse effects with a ribosomal agent: NVD, esophagitis, photosensitivity, renal toxicity if expired, tooth discoloration

tetracyclines

Match the adverse effects with a ribosomal agent: NVD, headache, hepatotoxicity

macrolides

Match the adverse effects with a ribosomal agent: rash, diarrhea, GI, C diff

lincosamides

Match the adverse effects with a ribosomal agent: bone marrow suppression, serotonin syndrome, optic neuritis, peripheral neuropathy

oxazolidinones

Match the adverse effects with a ribosomal agent: nephrotoxicity, ototoxicity

aminoglycosides

Match the MOA with a DNA inhibitor: analog of PABA, inhibits DHPS to block creation of dihydrofolic acid

sulfonamides

Match the MOA with a DNA inhibitor: inhibits dihydrofolate reductase synergistically with sulfonamides

trimethoprim

Match the MOA with a DNA inhibitor: prevents unwinding of strained DNA

fluoroquinolones

FQ that work ahead of the fork on DNA Gyrase are more common in ______

Gram -

FQ that work behind the fork on TOPO IV are more common in ____

Gram +

Match the MOA with a DNA inhibitor: prodrug that forms an anionic nitro radical to kill anaerobes

metronidazole

Match the adverse effects with the DNA inhibitor agent: hyperkalemia, hypersensitivity, hematological abnormalities

TMP-SMX

Match the adverse effects with the DNA inhibitor agent: QTc prolongation, CNS, c diff, dysglycemia, tendinopathy

fluoroquinolones

Match the adverse effects with the DNA inhibitor agent: disulfiram-like effect, dark urine, metallic taste, stomatitis

metronidazole

Match spectrum of activity of DNA inhibitor: very broad. covers Gram + like staph, enteric gram -, nocardia, fungi, protozoa

TMP-SMX

Match spectrum of activity of DNA inhibitor (FQ): gram - including Pseudo

ciprofloxacin

Match spectrum of activity of DNA inhibitor (FQ): gram - including pseudo, strep

levofloxacin

Match spectrum of activity of DNA inhibitor (FQ): gram - NOT including pseudo, strep, anaerobes

moxifloxacin

Match spectrum of activity of DNA inhibitor (FQ): gram - including Pseudo, strep, anaerobes, MRSA

delafloxacin

Match spectrum of activity of DNA inhibitor: anaerobes, protozoa

metronidazole

PK review of TMP-SMX:

• _____ inhibitor

• high Vd

CYP2C9

PK review of FQ:

• cipro/levo/dela are ____ eliminated

• moxi is _____ elimated

• which two require higher oral dosing to achieve same AUC?

renally; hepatically; cipro/dela

PK review of metronidazole:

• ____ oral bioavailability

• undergoes ___ and ____

• high Vd

90%, hepatic; renal

Match the non-beta lactam agent to its MOA: inhibits transglycosylation and transpeptidation; binds to D ALA D ALA to inhibit cross linkage of cell wall

vancomycin

Match the non-beta lactam agent to its MOA: depolarizes membrane by interfering with Ca

daptomycin

Match the non-beta lactam agent to its MOA: synthetic form just like vancomycin

dalbavancin

Match the non-beta lactam agent to its MOA: synthetic form just like vancomycin and daptomycin

oritavancin

Match the non-beta lactam agent to its MOA: inhibits MurA in the cell precursor in cytoplasm

fosfomycin

Non beta lactam agents are go-tos for _____, especially ____ and ____ in the instance of daptomycin

Gram +, MRSA, VRE

What 2 mechanisms of resistance are common in vancomycin

1. thickened cell wall

2. D ALA D Lac/Ser precursor

What 2 mechanisms of resistance are common in daptomycin

1. changes in outer membrane charge

2. thickened cell wall

What 2 mechanisms of resistance are common in fosfomycin

1. MurA mutation

2. enzyme degradation

PK overview of vancomycin:

• ____ cleared

• used ____ for systemic but ____ for C diff

renally; IV; PO

PK overview of daptomycin:

• ________ dosing

• ____ cleared

weight-based; renally

PK overview of dalbavancin/ortivancin:

• extremely _____ half life

long

Clinical pearl of fosfomycin

only clinically used for cystitis

What are the general monitoring parameters of vancomycin

trough, AUC/MIC, CrCl, CBC

What should be monitored while on daptomycin

CK

What should be monitored while on oritavancin

coagulation times

Which non-beta lactam causes nephrotoxicity, phlebitis, and infusion reactions

vancomycin

Which non-beta lactam causes rhabdomyolysis and eosinophilic pneumonia

daptomycin

Though it has covered for many Gram + drugs, daptomycin cannot be used to treat _____

pneumonia

DDI of daptomycin

statins (causes more rhabdomyolysis)

What is the MOA of beta-lactams

bind to PBPs to cause cell wall dysfunction

What are AE of beta-lactams

GI upset, allergic reactions

Adding a beta-lactamase inhibitor to an aminopenicillin increases its spectrum to cover ____ and ____

gram -, anaerobes

Which has greater gram - coverage: amoxicillin or oxacillin?

amoxicillin

Name the cephalosporin generation: covers Gram +

1st